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Jin Z, Liu K, Wallar G, Zhou J, Mu L, Liu X, Li L, He N, Wu M, Zhao J, Zhang Z. Environmental tobacco smoking (ETS) and esophageal cancer: A population-based case-control study in Jiangsu Province, China. Int J Cancer 2025; 156:1552-1562. [PMID: 39552259 PMCID: PMC11826109 DOI: 10.1002/ijc.35254] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2024] [Revised: 08/23/2024] [Accepted: 09/06/2024] [Indexed: 11/19/2024]
Abstract
Esophageal cancer continues to pose a significant public health issue in areas with increased incidence rates such as China. Although involuntary smoking was defined as a group 1 carcinogen for lung cancer, few studies have explored the impact of environmental tobacco smoking (ETS) on esophageal cancer. In this paper, we examined the association between ETS and esophageal cancer in high-risk groups in Jiangsu Province, China. Epidemiologic data were collected for 2969 newly diagnosed cases and 8019 population controls including exposure to active/passive smoking and risk factors. The unconditional logistic regression model and the semi-Bayes (SB) method were applied to assess adjusted odds ratios (ORs) and confidence intervals (CIs). ETS exposure (ever vs. never) was positively associated with esophageal cancer with an SB-adjusted OR (95% CI) of 1.44 (1.31-1.58) among overall population, and 1.56 (1.35-1.82) among non-smokers (i.e., non-active smokers), with corresponding population attributable fractions of 15.0% (95% CI: 10.3%-18.9%) and 12.1% (95% CI: 8.8%-19.8%), respectively. The association was more prominent in men at work and in women at home, with SB-adjusted OR (95% CI) of 1.36 (1.17-1.58) and 1.61 (1.35-1.58), respectively. A dose-response relationship between ETS exposure and the disease was detected across the entire population as well as in non-smokers. This is the largest population-based case-control study of ETS and esophageal cancer and the first study to evaluate such association among non-smokers in a Chinese population. We recommend strengthening the ongoing anti-tobacco public health initiatives in China with a particular emphasis on creating a tobacco-free work/home environment.
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Grants
- DA11386 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- CA90833 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- Alper Research Center for Environmental Genomics of the University of California, Los Angeles Jonsson Comprehensive Cancer Center
- R01 DA011386 NIDA NIH HHS
- CA96134 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- CA077954 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- R01 CA090833 NCI NIH HHS
- ES06718 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- RC 2003090 Jiangsu Provincial Health Department
- ES011667 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- T32 CA009142 NCI NIH HHS
- U01 CA096134 NCI NIH HHS
- CA09142 National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
- R03 CA077954 NCI NIH HHS
- R21 ES011667 NIEHS NIH HHS
- National Institutes of Health, National Institute of Environmental Health Sciences, National Cancer Institute, Department of Health and Human Services
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Affiliation(s)
- Zi‐Yi Jin
- Department of Epidemiology, School of Public HealthFudan UniversityShanghaiChina
- Nanjing Drum Tower HospitalClinical College of Nanjing Medical UniversityNanjingJiangsuChina
| | - Kuangyu Liu
- Department of Epidemiology, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Gina Wallar
- Department of Epidemiology, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Jin‐Yi Zhou
- Department of non‐communicable diseases prevention and controlJiangsu Provincial Center for Disease Control and PreventionNanjingJiangsuChina
| | - Li‐Na Mu
- Department of Social and Preventive Medicine, School of Public Health and Health ProfessionsUniversity at Buffalo, The State University of New YorkBuffaloNew YorkUSA
| | - Xing Liu
- Department of Epidemiology, School of Public HealthFudan UniversityShanghaiChina
- Department of Epidemiology, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
| | - Li‐Ming Li
- Department of Epidemiology, School of Public HealthPeking UniversityBeijingChina
| | - Na He
- Department of Epidemiology, School of Public HealthFudan UniversityShanghaiChina
| | - Ming Wu
- Department of non‐communicable diseases prevention and controlJiangsu Provincial Center for Disease Control and PreventionNanjingJiangsuChina
| | - Jin‐Kou Zhao
- Department of non‐communicable diseases prevention and controlJiangsu Provincial Center for Disease Control and PreventionNanjingJiangsuChina
| | - Zuo‐Feng Zhang
- Department of Epidemiology, Fielding School of Public HealthUniversity of CaliforniaLos AngelesCaliforniaUSA
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Sato S, Ohata E, Nakatani E, Hawke P, Sasaki H, Nagai E, Taki Y, Nishida M, Watanabe M, Ohata K, Kanemoto H, Sugawara A. High mean corpuscular volume as a predictor of esophageal cancer: A cohort study based on the Japanese Shizuoka Kokuho Database. PLoS One 2025; 20:e0318791. [PMID: 39932963 PMCID: PMC11813134 DOI: 10.1371/journal.pone.0318791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Accepted: 01/21/2025] [Indexed: 02/13/2025] Open
Abstract
Mean corpuscular volume (MCV) is known to increase with alcohol and tobacco consumption, and is therefore a potential predictive marker for esophageal cancer onset. However, this potential has not previously been examined using a large database. This study aims to clarify whether MCV is a predictor of esophageal cancer onset using health checkup data from a comprehensive health insurance claims database of a major administrative district in Japan. Health checkup data for 582,342 individuals recorded between April 2012 and September 2020 in the Shizuoka Kokuho Database were analyzed. Risk factors were assessed using both univariable and multivariable Cox proportional hazards models. Within the cohort, 1,562 health checkup participants (0.27%) had been diagnosed with esophageal cancer during the study period. Multivariable analysis revealed that risk of esophageal cancer onset was predicted by hypertension, smoking, systolic blood pressure, alcohol consumption, alcohol use disorder, body mass index, low-density lipoprotein cholesterol, and MCV. The cutoff value of MCV for predicting esophageal cancer onset was 104.086 fl. These results suggest that it may be appropriate to carry out endoscopy to detect esophageal cancer when MCV, a well-known indicator of alcohol and tobacco consumption, is greater than 104 fl.
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Affiliation(s)
- Shinsuke Sato
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Emi Ohata
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
- Department of Academic Services, Tokyo, Japan
| | - Eiji Nakatani
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
- Department of Biostatistics and Health Data Science, Graduate School of Medical Science, Nagoya City University, Nagoya, Japan
| | - Philip Hawke
- School of Pharmaceutical Sciences, University of Shizuoka, Shizuoka, Japan
| | - Hatoko Sasaki
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
| | - Erina Nagai
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Yusuke Taki
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Masato Nishida
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Masaya Watanabe
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Ko Ohata
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Hideyuki Kanemoto
- Department of Gastroenterological Surgery, Shizuoka General Hospital, Shizuoka, Japan
| | - Akira Sugawara
- Graduate School of Public Health, Shizuoka Graduate University of Public Health, Shizuoka, Japan
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Zhao R, Yuan H, Chen S, Xu K, Zhang T, Liu Z, Jiang Y, Suo C, Chen X. Impact of accelerated biological aging and genetic variation on esophageal adenocarcinoma: Joint and interaction effect in a prospective cohort. Int J Cancer 2025; 156:299-309. [PMID: 39233364 DOI: 10.1002/ijc.35161] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Revised: 08/12/2024] [Accepted: 08/15/2024] [Indexed: 09/06/2024]
Abstract
Accelerated biological aging may be associated with increased risk of esophageal adenocarcinoma (EAC). However, its relationship with genetic variation, and its effect on improving risk population stratification, remains unknown. We performed an exposome association study to determine potential associated factors associated with EAC. To quantify biological age and its difference from chronological age, we calculated the BioAge10 and Biological Age Acceleration (BioAgeAccel) based on chronological age and nine biomarkers. Multivariable Cox regression models for 362,310 participants from the UK Biobank with a median follow-up of 13.70 years were performed. We established a weighted polygenic risk score (wPRS) associated with EAC, to assess joint and interaction effects with BioAgeAccel. Four indicators were used to evaluate their interaction effects, and we fitted curves to evaluate the risk stratification ability of BioAgeAccel. Compared with biologically younger participants, those older had higher risk of EAC, with adjusted HR of 1.79 (95%CI: 1.52-2.10). Compared with low wPRS and biologically younger group, the high wPRS and biologically older group had a 4.30-fold increase in HR (95% CI: 2.78-6.66), at meanwhile, 1.15-fold relative excess risk was detected (95% CI: 0.30-2.75), and 22% of the overall EAC risk was attributable to the interactive effects (95% CI: 12%-31%). The 10-year absolute incidence risk indicates that biologically older individuals should begin screening procedures 4.18 years in advance, while youngers can postpone screening by 4.96 years, compared with general population. BioAgeAccel interacted positively with genetic variation and increased risk of EAC, it could serve as a novel indicator for predicting incidence.
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Affiliation(s)
- Renjia Zhao
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan University, Shanghai, China
| | - Huangbo Yuan
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan University, Shanghai, China
| | - Shuaizhou Chen
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
| | - Kelin Xu
- Department of Biostatistics, School of Public Health, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Tiejun Zhang
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Shanghai Institute of Infectious Disease and Biosecurity, Shanghai, China
| | - Zhenqiu Liu
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Yanfeng Jiang
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
| | - Chen Suo
- Department of Epidemiology, School of Public Health, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Shanghai Institute of Infectious Disease and Biosecurity, Shanghai, China
| | - Xingdong Chen
- State Key Laboratory of Genetic Engineering, Human Phenome Institute, Zhangjiang Fudan International Innovation Center, and School of Life Science, Fudan University, Shanghai, China
- Fudan University Taizhou Institute of Health Sciences, Taizhou, China
- Yiwu Research Institute of Fudan University, Yiwu, China
- National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University, Shanghai, China
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Ren ZT, Kang M, Zhu LY, Li P. Long-term survival and risk factors in esophageal squamous cell carcinoma: A Kaplan-Meier and cox regression study. World J Gastrointest Surg 2024; 16:3772-3779. [PMID: 39734461 PMCID: PMC11650227 DOI: 10.4240/wjgs.v16.i12.3772] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 09/10/2024] [Accepted: 09/12/2024] [Indexed: 11/27/2024] Open
Abstract
BACKGROUND The global incidence of esophageal cancer (EC) remains high. Despite advancements in medical technology and deeper research into the causes and treatment methods of EC, the effectiveness of treatment for EC is still unsatisfactory. Therefore, it is crucial to address the urgent problem of improving the long-term survival rate of EC patients and providing personalized treatment. AIM To analyze the survival prognosis and influencing factors of esophageal squamous cell carcinoma (ESCC). METHODS A retrospective analysis was conducted on the clinical data of 115 patients with pT3N0M0 ESCC who underwent radical surgery alone from January 1, 2013, to December 31, 2019. The Kaplan-Meier method was used to evaluate the 1-year, 3-year, and 5-year survival rates and median survival time of the patients. The Cox proportional hazards regression model was used to assess the hazard ratios (HRs) and 95% confidence intervals (95%CIs) of risk factors. RESULTS The 1-year, 3-year, and 5-year overall survival (OS) rates for the 115 EC patients analyzed were 85.22%, 50.43%, and 37.48%, respectively. The median OS was 37.00 (95%CI: 24.93-49.07) months, and the median disease-free survival was 21.00 (95%CI: 14.71-27.29) months. Both univariate and multivariate Cox regression analyses revealed that high body mass index (BMI; HR = 1.137, 95%CI: 1.054-1.226), positive perineural invasion (PNI; HR = 13.381, 95%CI: 4.899-36.547), and smoking (HR = 2.415, 95%CI: 1.388-4.203) were independent risk factors for a poor prognosis. In contrast, compared to the upper thoracic location of the tumor, middle thoracic (HR = 0.441, 95%CI: 0.240-0.810) and lower thoracic (HR = 0.328, 95%CI: 0.144-0.750) locations were protective factors. CONCLUSION BMI, tumor location, PNI, and smoking are associated with the prognosis of ESCC patients. This study highlights the prognostic risk factors for T3N0M0 ESCC patients and offers personalized insights for clinical treatment.
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Affiliation(s)
- Zheng-Ting Ren
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
| | - Mei Kang
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
| | - Li-Yang Zhu
- Department of Radiation Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
| | - Ping Li
- Oncology Department of Integrated Traditional Chinese and Western Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, Anhui Province, China
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Matsueda K, Manabe N, Watanabe T, Sato Y, Mizuno M, Haruma K. Adenocarcinoma of the esophagogastric junction: characteristics of female patients and young adult patients based on a 12-year retrospective and prospective multicenter clinicoepidemiological cohort study in Japan. BMC Gastroenterol 2024; 24:342. [PMID: 39354388 PMCID: PMC11443624 DOI: 10.1186/s12876-024-03421-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 09/16/2024] [Indexed: 10/03/2024] Open
Abstract
BACKGROUND Adenocarcinoma of the esophagogastric junction (AEGJ) is most common in men and the elderly, but the disease is becoming more common in female and young adult persons. We have investigated the clinicoepidemiological characteristics of female and young adult patients with AEGJ and the 12-year trends in the Kurashiki area for young adult patients with AEGJ. METHODS Patients diagnosed with AEGJ in 12 hospitals between January 2008 and December 2019 were included in this study. Patients were divided into three groups by age (young adult [≤50 years], middle-aged [51 to 70 years], and elderly [>70 years]). Factors associated with AEGJ such as obesity, smoking, hiatal hernia and male, which were reported in our previous study, were identified. RESULTS One hundred and eighty-eight AEGJ patients, including 36 females and 20 young adults, were characterized. There was no significant change in the annual incidence of AEGJ among female (p=0.078) and young adult patients (p=0.89). Female patients without any associated factors, accounting for 53% (19/36) of the female patients and young adult patients, had significantly more histologically undifferentiated cancers than patients with at least one associated factor (58% [11/19] vs. 30% [50/169], p=0.025) and middle-aged and elderly patients (60% [12/20] vs. 30% [25/83] vs. 28% [24/85], p =0.026). Smoking was significantly less common in women than in men (8% [3/36] vs. 57% [87/152], p < 0.01). There were no significant differences between ages in the proportions of these associated factors. CONCLUSIONS Histologically undifferentiated AEGJ cancers were more frequent in female patients without any associated factors and in young adult patients. Factors associated with AEGJ may differ between women and men, but they are similar in young adults and older adults. No increase in young adult patients with AEGJ was observed in the 12-year study.
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Affiliation(s)
- Kazuhiro Matsueda
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Noriaki Manabe
- Division of Endoscopy and Ultrasonography, Department of Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, 2-6-1 Nakasange, Kita-ku, Okayama, Okayama, 700-8505, Japan.
| | - Tetsuo Watanabe
- Watanabe Gastrointestinal Hospital, 539-5 Tamashimauwanari, Kurashiki, Okayama, 713-8101, Japan
| | - Yoshitaka Sato
- Sato Clinic Gastroenterology and Surgery, 3-13-1 Achi, Kurashiki, Okayama, 710-0055, Japan
| | - Motowo Mizuno
- Department of Gastroenterology and Hepatology, Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, 710-8602, Japan
| | - Ken Haruma
- Department of General Internal Medicine 2, Kawasaki Medical School, 2-6-1 Nakasange, Kita-ku, Okayama, Okayama, 700-8505, Japan
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Leiva O, Zarif TE, Alvarez-Cardona J. Gastrointestinal Cancer Therapy and Cardiotoxicity. Curr Treat Options Oncol 2024; 25:1203-1209. [PMID: 39102169 DOI: 10.1007/s11864-024-01236-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/18/2024] [Indexed: 08/06/2024]
Abstract
OPINION STATEMENT Gastrointestinal cancers are a heterogenous group of cancers that share common risk factors with cardiovascular disease. Therapy for gastrointestinal cancers have improved cancer-specific outcomes at the cost of cardiotoxicity. The most common cardiotoxic therapies utilized in gastrointestinal cancers include conventional chemotherapy (including fluoropyrimidines and anthracyclines), targeted therapies including anti-vascular endothelial growth factor (VEGF) therapy and tyrosine kinase inhibitors (TKI), and immunotherapy. It is important for clinicians managing patients with gastrointestinal cancers to be aware of potential cardiotoxicity associated with these agents.
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Affiliation(s)
- Orly Leiva
- Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, U.S.A
| | - Talal El Zarif
- Department of Medicine, Yale New Haven Health, New Haven, CT, U.S.A
| | - Jose Alvarez-Cardona
- Division of Cardiology, Department of Medicine, New York University Grossman School of Medicine, New York, NY, U.S.A..
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Peraza LR, Wallerius KP, Bowen AJ, Hernandez-Herrera GA, O'Byrne TJ, Aden AA, Bayan SL, Wong Kee Song LM, Ekbom DC. Effect of tobacco use on Zenker's diverticulotomy outcomes. Am J Otolaryngol 2024; 45:104261. [PMID: 38574513 DOI: 10.1016/j.amjoto.2024.104261] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2023] [Accepted: 03/17/2024] [Indexed: 04/06/2024]
Abstract
OBJECTIVE To compare clinical outcomes in patients with and without history of tobacco use who underwent Zenker's diverticulotomy (ZD). STUDY DESIGN Single institution retrospective review. SETTING Tertiary care academic hospital. METHODS A retrospective review of patients who underwent ZD via an open stapler, rigid endoscopic CO2 laser, stapler or harmonic scalpel, and flexible endoscopic technique from January 2006 to December 2020 was performed. Data were abstracted for patient demographics, diverticular features, and rates of adverse events and symptomatic recurrence. RESULTS Out of 424 patients, 146 (34.4 %) had a history of tobacco use: 126 (29.7 %) were former smokers, and 20 (4.7 %) were active smokers. In univariable cross-sectional analyses, the likelihood of postoperative bleeding, perforation, emergency department visits, unplanned readmission, or recurrence did not demonstrate an association with tobacco use history even after adjustment for age, sex, and surgical approach. Similarly, in Cox Proportional Hazards regression, tobacco use was not associated with an increased risk of recurrence, even after correcting for age, sex, and type of surgery. The median time to recurrence observed in our cohort was 11.5 years amongst non-smokers, 8.7 years amongst former smokers, and 1.2 years amongst active smokers (p = 0.94). CONCLUSIONS There were no significant differences in post-operative adverse events or frequency of recurrence of ZD between active, former, and non-smokers. Although underpowered and not statistically significant, median time to recurrence appears to be shorter in smokers when compared with former and non-smokers following surgery.
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Affiliation(s)
- Lazaro R Peraza
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA.
| | | | - Andrew J Bowen
- Department of Surgery, Division of Otolaryngology-Head and Neck Surgery, School of Medicine and Public Health, University of Wisconsin, Madison, WI, USA
| | | | - Thomas J O'Byrne
- Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN, USA
| | - Aisha A Aden
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA
| | - Semirra L Bayan
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA
| | | | - Dale C Ekbom
- Department of Otolaryngology-Head and Neck Surgery, Mayo Clinic, Rochester, MN, USA
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Abushamma S, Chen LS, Chen J, Smock N, Pham G, Chen CH. Enabling tobacco treatment for gastroenterology patients via a novel low-burden point-of-care model. BMC Health Serv Res 2024; 24:752. [PMID: 38902682 PMCID: PMC11188289 DOI: 10.1186/s12913-024-11092-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2023] [Accepted: 05/08/2024] [Indexed: 06/22/2024] Open
Abstract
BACKGROUND & AIM Smoking is a major risk factor for multiple gastrointestinal cancers, and adversely affects peptic ulcer disease, gastroesophageal reflux, pancreatitis and Crohn's disease. Despite key recommendations for diagnosing and treating tobacco use disorder in healthcare settings, the degree to which this is implemented in Gastroenterology (GI) clinics is unknown. We aimed to assess our providers' practices, identify barriers for implementing evidence-based smoking cessation treatments, and address these barriers by implementing a novel low-burden point of care Electronic health record-enabled evidence-based tobacco treatment (ELEVATE), in GI clinics. METHODS An online survey was distributed to clinic gastroenterologists. ELEVATE module training was implemented in 1/2021. Data were evaluated during pre (7/2020-12/2020) and post (1/2021-12/2021) implementation periods to evaluate the reach and effectiveness of ELEVATE. Generalized estimating equations (GEE) were used to generate rate ratios (RR) to evaluate the intervention. RESULTS 91% (20/22) of GI physicians responded to our survey, and only 20% often assisted patients who smoke with counseling. Lack of a systematic program to offer help to patients was reported by 80% of providers as an extremely/very important barrier limiting their smoking cessation practices. The proportion of current patients who smoke receiving cessation treatment increased from pre-ELEVATE to post-ELEVATE (14.36-27.47%, RR = 1.90, 95% CI 1.60-2.26, p < .001). Post-ELEVATE, 14.4% (38/264) of patients with treatment quit smoking, compared to 7.9% (55/697) of patients without treatment (RR = 1.89, 95% CI 1.26-2.82, p = .0021). CONCLUSION Smoking practices are frequently assessed in GI clinics but barriers limiting cessation treatment exist. The use of a low burden point of care EHR enabled smoking cessation treatment module has led to a significant improvement in the treatment of smoking and subsequent cessation in our clinics. This study sheds light on an often under-recognized source of morbidity in GI patients and identifies an efficient, effective, and scalable strategy to combat tobacco use and improve clinical outcomes in our patients.
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Affiliation(s)
- Suha Abushamma
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, 600 S. Euclid Avenue, MSC-8124-21-427, Saint Louis, MO, 63110, USA.
| | - Li-Shiun Chen
- Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, MO, USA
| | - Jingling Chen
- Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA
| | - Nina Smock
- Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA
- Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital, Washington University School of Medicine, Saint Louis, MO, USA
| | - Giang Pham
- Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA
| | - Chien-Huan Chen
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, 600 S. Euclid Avenue, MSC-8124-21-427, Saint Louis, MO, 63110, USA
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Rubenstein JH, Sawas T, Wani S, Eluri S, Singh S, Chandar AK, Perumpail RB, Inadomi JM, Thrift AP, Piscoya A, Sultan S, Singh S, Katzka D, Davitkov P. AGA Clinical Practice Guideline on Endoscopic Eradication Therapy of Barrett's Esophagus and Related Neoplasia. Gastroenterology 2024; 166:1020-1055. [PMID: 38763697 PMCID: PMC11345740 DOI: 10.1053/j.gastro.2024.03.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 05/21/2024]
Abstract
BACKGROUND & AIMS Barrett's esophagus (BE) is the precursor to esophageal adenocarcinoma (EAC). Endoscopic eradication therapy (EET) can be effective in eradicating BE and related neoplasia and has greater risk of harms and resource use than surveillance endoscopy. This clinical practice guideline aims to inform clinicians and patients by providing evidence-based practice recommendations for the use of EET in BE and related neoplasia. METHODS The Grading of Recommendations Assessment, Development and Evaluation framework was used to assess evidence and make recommendations. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients, conducted an evidence review, and used the Evidence-to-Decision Framework to develop recommendations regarding the use of EET in patients with BE under the following scenarios: presence of (1) high-grade dysplasia, (2) low-grade dysplasia, (3) no dysplasia, and (4) choice of stepwise endoscopic mucosal resection (EMR) or focal EMR plus ablation, and (5) endoscopic submucosal dissection vs EMR. Clinical recommendations were based on the balance between desirable and undesirable effects, patient values, costs, and health equity considerations. RESULTS The panel agreed on 5 recommendations for the use of EET in BE and related neoplasia. Based on the available evidence, the panel made a strong recommendation in favor of EET in patients with BE high-grade dysplasia and conditional recommendation against EET in BE without dysplasia. The panel made a conditional recommendation in favor of EET in BE low-grade dysplasia; patients with BE low-grade dysplasia who place a higher value on the potential harms and lower value on the benefits (which are uncertain) regarding reduction of esophageal cancer mortality could reasonably select surveillance endoscopy. In patients with visible lesions, a conditional recommendation was made in favor of focal EMR plus ablation over stepwise EMR. In patients with visible neoplastic lesions undergoing resection, the use of either endoscopic mucosal resection or endoscopic submucosal dissection was suggested based on lesion characteristics. CONCLUSIONS This document provides a comprehensive outline of the indications for EET in the management of BE and related neoplasia. Guidance is also provided regarding the considerations surrounding implementation of EET. Providers should engage in shared decision making based on patient preferences. Limitations and gaps in the evidence are highlighted to guide future research opportunities.
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Affiliation(s)
- Joel H Rubenstein
- Center for Clinical Management Research, Lieutenant Colonel Charles S. Kettles Veterans Affairs Medical Center, Ann Arbor, Michigan; Barrett's Esophagus Program, Division of Gastroenterology, University of Michigan Medical School, Ann Arbor, Michigan; Cancer Control and Population Sciences Program, Rogel Cancer Center, University of Michigan Medical School, Ann Arbor, Michigan.
| | - Tarek Sawas
- Division of Digestive and Liver Disease, University of Texas Southwestern, Dallas, Texas
| | - Sachin Wani
- Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora, Colorado
| | - Swathi Eluri
- Division of Gastroenterology and Hepatology, Mayo Clinic Florida, Jacksonville, Florida
| | - Shailendra Singh
- Division of Gastroenterology, West Virginia University, Morgantown, West Virginia; Advanced Center for Endoscopy, West Virginia University Medicine, Morgantown, West Virginia
| | - Apoorva K Chandar
- Digestive Health Institute, University Hospitals Cleveland Medical Center, Cleveland, Ohio
| | | | - John M Inadomi
- Department of Internal Medicine, The University of Utah School of Medicine, Salt Lake City, Utah
| | - Aaron P Thrift
- Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, Texas
| | | | - Shahnaz Sultan
- Division of Gastroenterology, Hepatology, and Nutrition, University of Minnesota, Minneapolis, Minnesota; Veterans Affairs Healthcare System, Minneapolis, Minnesota
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - David Katzka
- Division of Gastroenterology and Hepatology, Columbia University, New York, New York
| | - Perica Davitkov
- Department of Medicine, Case Western Reserve University, Cleveland, Ohio; Division of Gastroenterology, Veterans Affairs Northeast Ohio Healthcare System, Cleveland, Ohio
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Li C, Zhang J, Pan P, Zhang J, Hou X, Wang Y, Chen G, Muhammad P, Reis RL, Ding L, Wang Y. Humanistic Health Management and Cancer: Associations of Psychology, Nutrition, and Exercise with Cancer Progression and Pathogenesis. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2024; 11:e2400665. [PMID: 38526194 PMCID: PMC11165509 DOI: 10.1002/advs.202400665] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/18/2024] [Revised: 03/01/2024] [Indexed: 03/26/2024]
Abstract
The incidence rate of cancer is increasing year by year due to the aging of the population, unhealthy living, and eating habits. At present, surgery and medication are still the main treatments for cancer, without paying attention to the impact of individual differences in health management on cancer. However, increasing evidence suggests that individual psychological status, dietary habits, and exercise frequency are closely related to the risk and prognosis of cancer. The reminder to humanity is that the medical concept of the unified treatment plan is insufficient in cancer treatment, and a personalized treatment plan may become a breakthrough point. On this basis, the concept of "Humanistic Health Management" (HHM) is proposed. This concept is a healthcare plan that focuses on self-health management, providing an accurate and comprehensive evaluation of individual lifestyle habits, psychology, and health status, and developing personalized and targeted comprehensive cancer prevention and treatment plans. This review will provide a detailed explanation of the relationship between psychological status, dietary, and exercise habits, and the regulatory mechanisms of cancer. Intended to emphasize the importance of HHM concept in cancer prevention and better prognostic efficacy, providing new ideas for the new generation of cancer treatment.
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Affiliation(s)
- Chenchen Li
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Junfeng Zhang
- Tumor Precision Targeting Research Center & Institute of Nanochemistry and NanobiologySchool of Environmental and Chemical EngineeringShanghai UniversityShanghai200444P. R. China
| | - Pengcheng Pan
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Junjie Zhang
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Xinyi Hou
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Yan Wang
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Guoping Chen
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Pir Muhammad
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
| | - Rui L. Reis
- 3B's Research GroupI3Bs‐Research Institute on Biomaterials Biodegradables and BiomimeticsUniversity of MinhoGuimarães4805‐017Portugal
| | - Lin Ding
- Translational Medicine Collaborative Innovation CenterShenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and TechnologyThe Second Clinical Medical College of Jinan University)ShenzhenGuangdong518055P. R. China
- Guangdong Engineering Technology Research Center of Stem Cell and Cell TherapyShenzhen Key Laboratory of Stem Cell Research and Clinical TransformationShenzhen Immune Cell Therapy Public Service PlatformShenzhen518020P. R. China
| | - Yanli Wang
- International Joint Research Center of Human‐machine Intelligent Collaborative for Tumor Precision Diagnosis and Treatment of Hainan Province & Key Laboratory of Tropical Translational Medicine of Ministry of EducationSchool of Pharmacy & The First Affiliated HospitalHainan Medical UniversityHaikou571199P. R. China
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Akcam TI, Tekneci AK, Ergin TM, Memmedov R, Ergonul AG, Ozdil A, Turhan K, Cakan A, Cagırıcı U. Factors influencing postoperative recurrence of early-stage non-small cell lung cancer. Acta Chir Belg 2024; 124:121-130. [PMID: 37381717 DOI: 10.1080/00015458.2023.2231210] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Accepted: 06/25/2023] [Indexed: 07/06/2023]
Abstract
PURPOSE This study aims to explain the factors that may influence recurrence after surgical resection for early non-small cell lung cancer (NSCLC). METHODS A retrospective analysis was made of 302 patients who underwent lung resection for stage I-IIA NSCLC in our clinic between January 2014 and August 2021. RESULTS The recurrence rate was higher in patients with squamous cell carcinoma (SCC) than in those with adenocarcinoma (AC) (p = 0.004). Disease-free survival (DFS) was shorter in SCC (p = 0.004). According to histopathological subtypes, the presence of lymphovascular invasion (LVI), vascular invasion (VI), visceral pleural invasion (VPI) and tumor spread through air spaces (STAS) caused an increased risk of recurrence ((p = 0.004), (p = 0.001), (p = 0.047), (p = < 0.001)) and shorter DFS ((p = 0.002), (p = < 0.001), (p = 0.038), (p = < 0.001)). LVI and VI was more common in patients with distant recurrence (p = 0.020, p = 0.002), while the STAS was more common with locoregional recurrence (p = 0.003). CONCLUSION The presence of LVI, VI, VPI, and STAS are negative risk factors for recurrence and DFS in all patients and in patients with AC. In patients with SCC, the diagnosis of SCC itself and the presence of STAS were risk factors for recurrence and DFS. Moreover, the risk of distant recurrence is higher in the presence of LVI or VI, and the risk of locoregional recurrence in the presence of STAS is higher.
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Affiliation(s)
- Tevfik Ilker Akcam
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Ahmet Kayahan Tekneci
- Department of Thoracic Surgery, Health Sciences University İzmir Tepecik Education and Research Hospital, İzmir, Turkey
| | | | - Rza Memmedov
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Ayse Gul Ergonul
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Ali Ozdil
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Kutsal Turhan
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Alpaslan Cakan
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
| | - Ufuk Cagırıcı
- Department of Thoracic Surgery, Ege University School of Medicine, İzmir, Turkey
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12
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Yang K, Li S, Ding Y, Meng X, Zhang C, Sun X. Effect of smoking-related features and 731 immune cell phenotypes on esophageal cancer: a two-sample and mediated Mendelian randomized study. Front Immunol 2024; 15:1336817. [PMID: 38601154 PMCID: PMC11004242 DOI: 10.3389/fimmu.2024.1336817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2023] [Accepted: 03/18/2024] [Indexed: 04/12/2024] Open
Abstract
INTRODUCTION Numerous observational studies have indicated that smoking is a substantial risk factor for esophageal cancer. However, there is a shortage of research that delves into the specific causal relationship and potential mediators between the two. Our study aims to validate the correlation between smoking-related traits and esophageal cancer while exploring the possible mediating effects of immune factors. METHODS Initially, we conducted bidirectional univariate Mendelian Randomization (MR) analyses to forecast the causal effects linking smoking-related traits and esophageal cancer. Subsequently, we employed a two-step MR analysis to scrutinize immune cell phenotypes that could mediate these effects. Finally, the coefficient product method was employed to determine the precise mediating impact. Additionally, we have refined our sensitivity analysis to ensure the reliability of the outcomes. RESULTS After analysis, Smoking status: Never had a significant negative association with the incidence of esophageal cancer (inverse-variance weighted (IVW) method, p=1.82e-05, OR=0.10, 95%CI=0.04~0.29). Ever smoked (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) and Current tobacco smoking (IVW, p=1.49e-02, OR=4.31, 95%CI=1.33~13.94) showed the promoting effect on the pathogenesis of esophageal cancer. Through further examination, researchers discovered 21 immune cell phenotypes that have a causal relationship with esophageal cancer. After careful screening, two immune cell phenotypes were found to have potential mediating effects. In particular, it was observed that in the case of the preventive effect of Smoking status: Never on esophageal cancer, the absolute count of CD62L plasmacytoid dendritic cells mediated a reduction of 4.21%, while the mediating effect of CD27 in CD20-CD38-B cells was -4.12%. In addition, sensitivity analyses did not reveal significant heterogeneity or level pleiotropy. CONCLUSION The study provides new evidence for the causal relationship between smoking-related features and esophageal cancer and proposes immune factors with potential mediating effects. However, this finding needs to be further demonstrated by more extensive clinical studies.
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Affiliation(s)
| | | | | | | | | | - Xiujing Sun
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, China
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13
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Rota M, Possenti I, Valsassina V, Santucci C, Bagnardi V, Corrao G, Bosetti C, Specchia C, Gallus S, Lugo A. Dose-response association between cigarette smoking and gastric cancer risk: a systematic review and meta-analysis. Gastric Cancer 2024; 27:197-209. [PMID: 38231449 DOI: 10.1007/s10120-023-01459-1] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/28/2023] [Accepted: 12/16/2023] [Indexed: 01/18/2024]
Abstract
This study aims at providing an accurate and up-to-date quantification of the dose-response association between cigarette smoking and gastric cancer (GC) risk, overall and by subsite. We conducted a systematic review and meta-analysis of case-control and cohort studies on the association between cigarette smoking and GC risk published up to January 2023. We estimated pooled relative risks (RR) of GC and its subsites according to smoking status, intensity, duration, and time since quitting. Among 271 eligible articles, 205 original studies were included in this meta-analysis. Compared with never smokers, the pooled RR for GC was 1.53 (95% confidence interval; CI 1.44-1.62; n = 92) for current and 1.30 (95% CI 1.23-1.37; n = 82) for former smokers. The RR for current compared with never smokers was 2.08 (95% CI 1.66-2.61; n = 21) for gastric cardia and 1.48 (95% CI 1.33-1.66; n = 8) for distal stomach cancer. GC risk nonlinearly increased with smoking intensity up to 20 cigarettes/day (RR:1.69; 95% CI 1.55-1.84) and levelled thereafter. GC risk significantly increased linearly with increasing smoking duration (RR: 1.31; 95% CI 1.25-1.37 for 20 years) and significantly decreased linearly with increasing time since quitting (RR: 0.65; 95% CI 0.44-0.95 for 30 years since cessation). The present meta-analysis confirms that cigarette smoking is an independent risk factor for GC, particularly for gastric cardia. GC risk increases with a low number of cigarettes up to 20 cigarettes/day and increases in a dose-dependent manner with smoking duration.
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Affiliation(s)
- Matteo Rota
- Department of Molecular and Translational Medicine, Università Degli Studi Di Brescia, Brescia, Italy
| | - Irene Possenti
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy
| | - Valeria Valsassina
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy
| | - Claudia Santucci
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy
- Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
| | - Vincenzo Bagnardi
- Department of Statistics and Quantitative Methods, Università Degli Studi Di Milano-Bicocca, Milan, Italy
| | - Giovanni Corrao
- Laboratory of Healthcare Research and Pharmacoepidemiology, Unit of Biostatistics, Epidemiology and Public Health, Department of Statistics and Quantitative Methods, University of Milano-Bicocca, Milan, Italy
- National Centre of Healthcare Research and Pharmacoepidemiology, University of Milano-Bicocca, Milan, Italy
| | - Cristina Bosetti
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy
| | - Claudia Specchia
- Department of Molecular and Translational Medicine, Università Degli Studi Di Brescia, Brescia, Italy
| | - Silvano Gallus
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy
| | - Alessandra Lugo
- Department of Medical Epidemiology, Istituto Di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy.
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Wu G, Wu Q, Xu J, Gao G, Chen T, Chen G. Mortality burden and future projections of major risk factors for esophageal cancer in China from 1990 to 2019. Gen Thorac Cardiovasc Surg 2024; 72:192-201. [PMID: 37973657 DOI: 10.1007/s11748-023-01987-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2023] [Accepted: 10/25/2023] [Indexed: 11/19/2023]
Abstract
OBJECTIVE This study, based on Global Burden of Disease (GBD) data, aimed to report the long-term trend in mortality rates caused by risk factors for esophageal cancer (EC) in China from 1990 to 2019 and predict the burden of EC mortality caused by these risk factors over the next 15 years. METHODS We examined six risk factors that influenced EC mortality rates in China and their respective rankings. Furthermore, we analyzed the number of deaths and crude mortality rates (CMR) caused by these risk factors for both sexes and different age groups. Age-standardized mortality rates (ASMR) and the number of deaths across all age groups were also analyzed. Finally, we utilized the Bayesian Age-Period-Cohort (BAPC) model to predict the trends in ASMR burden caused by these risk factors in the future. RESULTS From 1990 to 2019, the percentage changes in ASMR for EC caused by the six risk factors in China were as follows: smoking (- 33.4%), alcohol consumption (- 23.0%), low fruit intake (- 73.6%), low vegetable intake (- 96.0%), high Body Mass Index (BMI) (25.1%), and tobacco chewing (- 32.8%). In 2019, the top three risk factors contributing to EC ASMR in China were smoking, alcohol consumption, and high BMI. Overall, the ASMR for EC in China fluctuated and declined from 1990 to 2019. The most common risk factors for males were smoking and alcohol consumption, while low fruit intake and high BMI were the most common risk factors for females. The impact of these risk factors on EC mortality increased with age, except for the elderly population. BAPC analysis indicated that the influence of these risk factors on ASMR was expected to remain relatively stable in the next 15 years, suggesting a continued significant burden of EC. CONCLUSION The projected burden of EC mortality in China was expected to continue increasing steadily over the next 15 years, highlighting the pressing need for disease control measures. To alleviate this burden, targeted prevention and control policies addressing risk factors for EC such as smoking, alcohol consumption, and high BMI are necessary.
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Affiliation(s)
- Guibin Wu
- Department of Medical Oncology, Anxi County Hospital, No. 249-259, Hebin South Road, Fengcheng Town, Anxi County, 362400, Fujian Province, China.
| | - Qingxiang Wu
- Blood Purification Centre, Anxi County Hospital, Anxi County, 362400, Fujian Province, China
| | - Juan Xu
- Department of Medical Oncology, Anxi County Hospital, No. 249-259, Hebin South Road, Fengcheng Town, Anxi County, 362400, Fujian Province, China
| | - Genhua Gao
- Department of Medical Oncology, Anxi County Hospital, No. 249-259, Hebin South Road, Fengcheng Town, Anxi County, 362400, Fujian Province, China
| | - Tingting Chen
- Department of Medical Oncology, Anxi County Hospital, No. 249-259, Hebin South Road, Fengcheng Town, Anxi County, 362400, Fujian Province, China
| | - Guowei Chen
- Department of Medical Oncology, Anxi County Hospital, No. 249-259, Hebin South Road, Fengcheng Town, Anxi County, 362400, Fujian Province, China
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Muhammad Nawawi KN, El‐Omar EM, Ali RA. Screening, Surveillance, and Prevention of Esophageal and Gastric Cancers. GASTROINTESTINAL ONCOLOGY ‐ A CRITICAL MULTIDISCIPLINARY TEAM APPROACH 2E 2024:42-62. [DOI: 10.1002/9781119756422.ch3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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16
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Kim N. Esophageal Diseases. SEX/GENDER-SPECIFIC MEDICINE IN CLINICAL AREAS 2024:55-93. [DOI: 10.1007/978-981-97-0130-8_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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17
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Schlueter DJ, Sulieman L, Mo H, Keaton JM, Ferrara TM, Williams A, Qian J, Stubblefield O, Zeng C, Tran TC, Bastarache L, Dai J, Babbar A, Ramirez A, Goleva SB, Denny JC. Systematic replication of smoking disease associations using survey responses and EHR data in the All of Us Research Program. J Am Med Inform Assoc 2023; 31:139-153. [PMID: 37885303 PMCID: PMC10746325 DOI: 10.1093/jamia/ocad205] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2023] [Revised: 05/04/2023] [Accepted: 10/12/2023] [Indexed: 10/28/2023] Open
Abstract
OBJECTIVE The All of Us Research Program (All of Us) aims to recruit over a million participants to further precision medicine. Essential to the verification of biobanks is a replication of known associations to establish validity. Here, we evaluated how well All of Us data replicated known cigarette smoking associations. MATERIALS AND METHODS We defined smoking exposure as follows: (1) an EHR Smoking exposure that used International Classification of Disease codes; (2) participant provided information (PPI) Ever Smoking; and, (3) PPI Current Smoking, both from the lifestyle survey. We performed a phenome-wide association study (PheWAS) for each smoking exposure measurement type. For each, we compared the effect sizes derived from the PheWAS to published meta-analyses that studied cigarette smoking from PubMed. We defined two levels of replication of meta-analyses: (1) nominally replicated: which required agreement of direction of effect size, and (2) fully replicated: which required overlap of confidence intervals. RESULTS PheWASes with EHR Smoking, PPI Ever Smoking, and PPI Current Smoking revealed 736, 492, and 639 phenome-wide significant associations, respectively. We identified 165 meta-analyses representing 99 distinct phenotypes that could be matched to EHR phenotypes. At P < .05, 74 were nominally replicated and 55 were fully replicated. At P < 2.68 × 10-5 (Bonferroni threshold), 58 were nominally replicated and 40 were fully replicated. DISCUSSION Most phenotypes found in published meta-analyses associated with smoking were nominally replicated in All of Us. Both survey and EHR definitions for smoking produced similar results. CONCLUSION This study demonstrated the feasibility of studying common exposures using All of Us data.
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Affiliation(s)
- David J Schlueter
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
- Department of Health and Society, University of Toronto, Scarborough, Toronto, ON, Canada
| | - Lina Sulieman
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Huan Mo
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
- The Cohort Analytics Core (CAC), Center for Precision Health Research, National Human Genome Research Institute, Bethesda, MD, USA
| | - Jacob M Keaton
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Tracey M Ferrara
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Ariel Williams
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Jun Qian
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Onajia Stubblefield
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Chenjie Zeng
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Tam C Tran
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
- The Cohort Analytics Core (CAC), Center for Precision Health Research, National Human Genome Research Institute, Bethesda, MD, USA
| | - Lisa Bastarache
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Jian Dai
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Anav Babbar
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Andrea Ramirez
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
- Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States
| | - Slavina B Goleva
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
| | - Joshua C Denny
- Precision Health Informatics Section, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, United States
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Jackson JC, Molena D, Amar D. Evolving Perspectives on Esophagectomy Care: Clinical Update. Anesthesiology 2023; 139:868-879. [PMID: 37812764 PMCID: PMC10843679 DOI: 10.1097/aln.0000000000004720] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/11/2023]
Abstract
Recent changes in perioperative care have led to new perspectives and important advances that have helped to improve outcomes among patients treated with esophagectomy for esophageal cancer.
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Affiliation(s)
- Jacob C. Jackson
- Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Weill Cornell Medical College, New York, New York
| | - Daniela Molena
- Weill Cornell Medical College, New York, New York
- Thoracic Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York
| | - David Amar
- Department of Anesthesiology and Critical Care Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
- Weill Cornell Medical College, New York, New York
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Kwon MJ, Kang HS, Choi HG, Kim JH, Kim JH, Bang WJ, Hong SK, Kim NY, Hong S, Lee HK. Risk for Esophageal Cancer Based on Lifestyle Factors-Smoking, Alcohol Consumption, and Body Mass Index: Insight from a South Korean Population Study in a Low-Incidence Area. J Clin Med 2023; 12:7086. [PMID: 38002698 PMCID: PMC10672319 DOI: 10.3390/jcm12227086] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2023] [Revised: 11/06/2023] [Accepted: 11/08/2023] [Indexed: 11/26/2023] Open
Abstract
Esophageal cancer constitutes a global public health challenge. However, South Korean population-specific information on the association of lifestyle (smoking, alcohol consumption, and obesity status) with esophageal cancer risk is sparse. This nested case-control study analyzed the Korean national health screening cohort data (2002-2019) of 1114 patients with esophageal cancer and 4456 controls (1:4 propensity-score matched for sex, age, income, and residential region). Conditional and unconditional logistic regression analyses, after adjustment for multiple covariates, determined the effects of lifestyle factors on esophageal cancer risk. Smoking and alcohol consumption increased the esophageal cancer risk (adjusted odds ratio [95% confidence interval]: 1.37 [1.15-1.63] and 1.89 [1.60-2.23], respectively). Overweight (body mass index [BMI] ≥ 23 to <25 kg/m2), obese I (BMI ≥ 25 to <30 kg/m2), or obese II (BMI ≥ 30 kg/m2) categories had reduced odds of esophageal cancer (0.76 [0.62-0.92], 0.59 [0.48-0.72], and 0.47 [0.26-0.85], respectively). In the subgroup analyses, the association of incident esophageal cancer with smoking and alcohol consumption persisted, particularly in men or those aged ≥55 years, whereas higher BMI scores remained consistently associated with a reduced esophageal cancer likelihood across all age groups, in both sexes, and alcohol users or current smokers. Underweight current smokers exhibited a higher propensity for esophageal cancer. In conclusion, smoking and alcohol drinking may potentially increase the risk, whereas weight maintenance, with BMI ≥ 23 kg/m2, may potentially decrease the risk, for esophageal cancer in the South Korean population. Lifestyle modification in the specific subgroups may be a potential strategy for preventing esophageal cancer.
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Affiliation(s)
- Mi Jung Kwon
- Department of Pathology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Ho Suk Kang
- Division of Gastroenterology, Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Hyo Geun Choi
- Suseo Seoul E.N.T. Clinic and MD Analytics, 10, Bamgogae-ro 1-gil, Gangnam-gu, Seoul 06349, Republic of Korea;
| | - Joo-Hee Kim
- Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Ji Hee Kim
- Department of Neurosurgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Woo Jin Bang
- Department of Urology, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Sung Kwang Hong
- Department of Otorhinolaryngology-Head & Neck Surgery, Hallym University College of Medicine, Anyang 14068, Republic of Korea;
| | - Nan Young Kim
- Hallym Institute of Translational Genomics and Bioinformatics, Hallym University Medical Center, Anyang 14068, Republic of Korea; (N.Y.K.); (S.H.)
| | - Sangkyoon Hong
- Hallym Institute of Translational Genomics and Bioinformatics, Hallym University Medical Center, Anyang 14068, Republic of Korea; (N.Y.K.); (S.H.)
| | - Hong Kyu Lee
- Department of Thoracic and Cardiovascular Surgery, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang 14068, Republic of Korea
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20
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Islam MO, Thangaretnam K, Lu H, Peng D, Soutto M, El-Rifai W, Giordano S, Ban Y, Chen X, Bilbao D, Villarino AV, Schürer S, Hosein PJ, Chen Z. Smoking induces WEE1 expression to promote docetaxel resistance in esophageal adenocarcinoma. Mol Ther Oncolytics 2023; 30:286-300. [PMID: 37732296 PMCID: PMC10507159 DOI: 10.1016/j.omto.2023.08.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 08/24/2023] [Indexed: 09/22/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) patients have poor clinical outcomes, with an overall 5-year survival rate of 20%. Smoking is a significant risk factor for EAC. The role of WEE1, a nuclear kinase that negatively regulates the cell cycle in normal conditions, in EAC tumorigenesis and drug resistance is not fully understood. Immunohistochemistry staining shows significant WEE1 overexpression in human EAC tissues. Nicotine, nicotine-derived nitrosamine ketone, or 2% cigarette smoke extract treatment induces WEE1 protein expression in EAC, detected by western blot and immunofluorescence staining. qRT-PCR and reporter assay indicates that smoking induces WEE1 expression through miR-195-5p downregulation in EAC. ATP-Glo cell viability and clonogenic assay confirmed that WEE1 inhibition sensitizes EAC cells to docetaxel treatment in vitro. A TE-10 smoking machine with EAC patient-derived xenograft mouse model demonstrated that smoking induces WEE1 protein expression and resistance to docetaxel in vivo. MK-1775 and docetaxel combined treatment improves EAC patient-derived xenograft mouse survival in vivo. Our findings demonstrate, for the first time, that smoking-induced WEE1 overexpression through miRNA dysregulation in EAC plays an essential role in EAC drug resistance. WEE1 inhibition is a promising therapeutic method to overcome drug resistance and target treatment refractory cancer cells.
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Affiliation(s)
- Md Obaidul Islam
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Krishnapriya Thangaretnam
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Heng Lu
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Dunfa Peng
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Mohammed Soutto
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
| | - Wael El-Rifai
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
- Department of Veterans Affairs, Miami Healthcare System, Miami, FL 33136, USA
| | - Silvia Giordano
- University of Torino, Candiolo Cancer Institute - FPO, IRCCS, 10060 Candiolo, Italy
| | - Yuguang Ban
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Xi Chen
- Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Daniel Bilbao
- Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
- Department of Pathology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Alejandro V. Villarino
- Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
- Department of Microbiology and Immunology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Stephan Schürer
- Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
- Institute for Data Science and Computing, University of Miami, Coral Gables, FL 33146, USA
| | - Peter J. Hosein
- Sylvester Comprehensive Cancer Center, Miami, FL 33136, USA
- Department of Molecular and Cellular Pharmacology, Miller School of Medicine, University of Miami, Miami, FL 33136, USA
| | - Zheng Chen
- Department of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA
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21
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Ansari KK, Wagh V, Saifi AI, Saifi I, Chaurasia S. Advancements in Understanding Gastric Cancer: A Comprehensive Review. Cureus 2023; 15:e46046. [PMID: 37900456 PMCID: PMC10611549 DOI: 10.7759/cureus.46046] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2023] [Accepted: 09/22/2023] [Indexed: 10/31/2023] Open
Abstract
As a complex and difficult condition, gastric cancer (GC) continues to have a big impact on the world's health. The goal of this review article is to give a thorough summary of the most recent developments and research discoveries in the field of stomach cancer. The review discusses a wide range of topics, such as the epidemiology and risk factors for GC, molecular insights into its pathogenesis, the use of biomarkers in diagnosis and prognosis, current and novel therapeutic approaches, and the intriguing potential of immunotherapy. In addition, procedures for surgery, therapy strategies, and imaging modalities for diagnosis and staging are examined. The paper emphasizes how crucial it is to comprehend the tumor microenvironment and how it affects the course of the disease. Overall, this review provides a comprehensive assessment of the current body of knowledge, highlights research gaps, and suggests future lines of inquiry to enhance the treatment of GC.
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Affiliation(s)
- Khizer K Ansari
- Medicine and Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Vasant Wagh
- Community Medicine, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Azeem I Saifi
- Microbiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Iram Saifi
- Radiology, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
| | - Sharad Chaurasia
- Medicine and Surgery, Jawaharlal Nehru Medical College, Datta Meghe Institute of Higher Education & Research, Wardha, IND
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22
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Abbas S, Pich O, Devonshire G, Zamani SA, Katz-Summercorn A, Killcoyne S, Cheah C, Nutzinger B, Grehan N, Lopez-Bigas N, Fitzgerald RC, Secrier M. Mutational signature dynamics shaping the evolution of oesophageal adenocarcinoma. Nat Commun 2023; 14:4239. [PMID: 37454136 PMCID: PMC10349863 DOI: 10.1038/s41467-023-39957-6] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Accepted: 07/03/2023] [Indexed: 07/18/2023] Open
Abstract
A variety of mutational processes drive cancer development, but their dynamics across the entire disease spectrum from pre-cancerous to advanced neoplasia are poorly understood. We explore the mutagenic processes shaping oesophageal adenocarcinoma tumorigenesis in 997 instances comprising distinct stages of this malignancy, from Barrett Oesophagus to primary tumours and advanced metastatic disease. The mutational landscape is dominated by the C[T > C/G]T substitution enriched signatures SBS17a/b, which are linked with TP53 mutations, increased proliferation, genomic instability and disease progression. The APOBEC mutagenesis signature is a weak but persistent signal amplified in primary tumours. We also identify prevalent alterations in DNA damage repair pathways, with homologous recombination, base and nucleotide excision repair and translesion synthesis mutated in up to 50% of the cohort, and surprisingly uncoupled from transcriptional activity. Among these, the presence of base excision repair deficiencies show remarkably poor prognosis in the cohort. In this work, we provide insights on the mutational aetiology and changes enabling the transition from pre-neoplastic to advanced oesophageal adenocarcinoma.
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Affiliation(s)
- Sujath Abbas
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | - Oriol Pich
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
| | - Ginny Devonshire
- Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, UK
| | | | | | - Sarah Killcoyne
- Early Cancer Institute, University of Cambridge, Cambridge, UK
- European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
| | - Calvin Cheah
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | | | - Nicola Grehan
- Early Cancer Institute, University of Cambridge, Cambridge, UK
| | - Nuria Lopez-Bigas
- Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology, Barcelona, Spain
- Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain
- Centro de Investigación Biomédica en Red en Cáncer (CIBERONC), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Maria Secrier
- UCL Genetics Institute, Department of Genetics, Evolution and Environment, University College London, London, UK.
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23
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Yang X, Chen H, Zhang S, Chen X, Sheng Y, Pang J. Association of cigarette smoking habits with the risk of prostate cancer: a systematic review and meta-analysis. BMC Public Health 2023; 23:1150. [PMID: 37316851 DOI: 10.1186/s12889-023-16085-w] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Accepted: 06/09/2023] [Indexed: 06/16/2023] Open
Abstract
BACKGROUND Association of cigarette smoking habits with the risk of prostate cancer is still a matter of debate. This systematic review and meta-analysis aimed to assess the association between cigarette smoking and prostate cancer risk. METHODS We conducted a systematic search on PubMed, Embase, Cochrane Library, and Web of Science without language or time restrictions on June 11, 2022. Literature search and study screening were performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Prospective cohort studies that assessed the association between cigarette smoking habits and the risk of prostate cancer were included. Quality assessment was conducted using the Newcastle-Ottawa Scale. We used random-effects models to obtain pooled estimates and the corresponding 95% confidence intervals. RESULTS A total of 7296 publications were screened, of which 44 cohort studies were identified for qualitative analysis; 39 articles comprising 3 296 398 participants and 130 924 cases were selected for further meta-analysis. Current smoking had a significantly reduced risk of prostate cancer (RR, 0.74; 95% CI, 0.68-0.80; P < 0.001), especially in studies completed in the prostate-specific antigen screening era. Compared to former smokers, current smokers had a significant lower risk of PCa (RR, 0.70; 95% CI, 0.65-0.75; P < 0.001). Ever smoking showed no association with prostate cancer risk in overall analyses (RR, 0.96; 95% CI, 0.93-1.00; P = 0.074), but an increased risk of prostate cancer in the pre-prostate-specific antigen screening era (RR, 1.05; 95% CI, 1.00-1.10; P = 0.046) and a lower risk of prostate cancer in the prostate-specific antigen screening era (RR, 0.95; 95% CI, 0.91-0.99; P = 0.011) were observed. Former smoking did not show any association with the risk of prostate cancer. CONCLUSIONS The findings suggest that the lower risk of prostate cancer in smokers can probably be attributed to their poor adherence to cancer screening and the occurrence of deadly smoking-related diseases, and we should take measures to help smokers to be more compliant with early cancer screening and to quit smoking. TRIAL REGISTRATION This study was registered on PROSPERO (CRD42022326464).
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Affiliation(s)
- Xiangwei Yang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, No.628 Zhenyuan Road, Shenzhen, 518107, China
| | - Hong Chen
- School of Nursing, LKS Faculty of Medicine, University of Hong Kong, Hong Kong, China
| | - Shiqiang Zhang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, No.628 Zhenyuan Road, Shenzhen, 518107, China
| | - Xianju Chen
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, No.628 Zhenyuan Road, Shenzhen, 518107, China
| | - Yiyu Sheng
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, No.628 Zhenyuan Road, Shenzhen, 518107, China
| | - Jun Pang
- Department of Urology, Kidney and Urology Center, Pelvic Floor Disorders Center, The Seventh Affiliated Hospital, Sun Yat-Sen University, No.628 Zhenyuan Road, Shenzhen, 518107, China.
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24
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Xi S, Oyetunji S, Wang H, Azoury S, Liu Y, Hsiao SH, Zhang M, Carr SR, Hoang CD, Chen H, Schrump DS. Cigarette Smoke Enhances the Malignant Phenotype of Esophageal Adenocarcinoma Cells by Disrupting a Repressive Regulatory Interaction Between miR-145 and LOXL2. J Transl Med 2023; 103:100014. [PMID: 36870293 PMCID: PMC10121750 DOI: 10.1016/j.labinv.2022.100014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2021] [Revised: 08/24/2022] [Accepted: 09/19/2022] [Indexed: 01/11/2023] Open
Abstract
Although linked to esophageal carcinogenesis, the mechanisms by which cigarette smoke mediates initiation and progression of esophageal adenocarcinomas (EAC) have not been fully elucidated. In this study, immortalized esophageal epithelial cells and EAC cells (EACCs) were cultured with or without cigarette smoke condensate (CSC) under relevant exposure conditions. Endogenous levels of microRNA (miR)-145 and lysyl-likeoxidase 2 (LOXL2) were inversely correlated in EAC lines/tumors compared with that in immortalized cells/normal mucosa. The CSC repressed miR-145 and upregulated LOXL2 in immortalized esophageal epithelial cells and EACCs. Knockdown or constitutive overexpression of miR-145 activated or depleted LOXL2, respectively, which enhanced or reduced proliferation, invasion, and tumorigenicity of EACC, respectively. LOXL2 was identified as a novel target of miR-145 as well as a negative regulator of this miR in EAC lines/Barrett's epithelia. Mechanistically, CSC induced recruitment of SP1 to the LOXL2 promoter; LOXL2 upregulation coincided with LOXL2 enrichment and concomitant reduction of H3K4me3 levels within the promoter of miR143HG (host gene for miR-145). Mithramycin downregulated LOXL2 and restored miR-145 expression in EACC and abrogated LOXL2-mediated repression of miR-145 by CSC. These findings implicate cigarette smoke in the pathogenesis of EAC and demonstrate that oncogenic miR-145-LOXL2 axis dysregulation is potentially druggable for the treatment and possible prevention of these malignancies.
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Affiliation(s)
- Sichuan Xi
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Shakirat Oyetunji
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Haitao Wang
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Said Azoury
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Yi Liu
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Shih-Hsin Hsiao
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Mary Zhang
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Shamus R Carr
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Chuong D Hoang
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - Haobin Chen
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland
| | - David S Schrump
- Thoracic Epigenetics Section, Thoracic Surgery Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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25
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Beydoun AS, Stabenau KA, Altman KW, Johnston N. Cancer Risk in Barrett's Esophagus: A Clinical Review. Int J Mol Sci 2023; 24:ijms24076018. [PMID: 37046992 PMCID: PMC10094310 DOI: 10.3390/ijms24076018] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Revised: 03/21/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
Esophageal adenocarcinoma (EAC) is rapidly increasing in incidence and is associated with a poor prognosis. Barrett's esophagus (BE) is a known precursor of esophageal adenocarcinoma. This review aims to explore Barrett's esophagus, esophageal adenocarcinoma, and the progression from the former to the latter. An overview of the definition, diagnosis, epidemiology, and risk factors for both entities are presented, with special attention being given to the areas of debate in the literature. The progression from Barrett's esophagus to esophageal adenocarcinoma is reviewed and the relevant molecular pathways are discussed. The definition of Barrett's esophagus remains debated and without international consensus. This, alongside other factors, has made establishing the true prevalence of Barrett's esophagus challenging. The degree of dysplasia can be a histological challenge, but is necessary to guide clinical management. The progression of BE to EAC is likely driven by inflammatory pathways, pepsin exposure, upregulation of growth factor pathways, and mitochondrial changes. Surveillance is maintained through serial endoscopic evaluation, with shorter intervals recommended for high-risk features.
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Affiliation(s)
- Ahmed Sam Beydoun
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kaleigh A Stabenau
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
| | - Kenneth W Altman
- Department of Otolaryngology-Head & Neck Surgery, Geisinger Medical Center, Danville, PA 17822, USA
| | - Nikki Johnston
- Department of Otolaryngology and Communication Sciences, Medical College of Wisconsin, Milwaukee, WI 53226, USA
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26
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Kratzer TB, Jemal A, Miller KD, Nash S, Wiggins C, Redwood D, Smith R, Siegel RL. Cancer statistics for American Indian and Alaska Native individuals, 2022: Including increasing disparities in early onset colorectal cancer. CA Cancer J Clin 2023; 73:120-146. [PMID: 36346402 DOI: 10.3322/caac.21757] [Citation(s) in RCA: 67] [Impact Index Per Article: 33.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2022] [Revised: 08/24/2022] [Accepted: 08/30/2022] [Indexed: 11/09/2022] Open
Abstract
American Indian and Alaska Native (AIAN) individuals are diverse culturally and geographically but share a high prevalence of chronic illness, largely because of obstacles to high-quality health care. The authors comprehensively examined cancer incidence and mortality among non-Hispanic AIAN individuals, compared with non-Hispanic White individuals for context, using population-based data from the National Cancer Institute, the Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries. Overall cancer rates among AIAN individuals were 2% higher than among White individuals for incidence (2014 through 2018, confined to Purchased/Referred Care Delivery Area counties to reduce racial misclassification) but 18% higher for mortality (2015 through 2019). However, disparities varied widely by cancer type and geographic region. For example, breast and prostate cancer mortality rates are 8% and 31% higher, respectively, in AIAN individuals than in White individuals despite lower incidence and the availability of early detection tests for these cancers. The burden among AIAN individuals is highest for infection-related cancers (liver, stomach, and cervix), for kidney cancer, and for colorectal cancer among indigenous Alaskans (91.3 vs. 35.5 cases per 100,000 for White Alaskans), who have the highest rates in the world. Steep increases for early onset colorectal cancer, from 18.8 cases per 100,000 Native Alaskans aged 20-49 years during 1998 through 2002 to 34.8 cases per 100,000 during 2014 through 2018, exacerbated this disparity. Death rates for infection-related cancers (liver, stomach, and cervix), as well as kidney cancer, were approximately two-fold higher among AIAN individuals compared with White individuals. These findings highlight the need for more effective strategies to reduce the prevalence of chronic oncogenic infections and improve access to high-quality cancer screening and treatment for AIAN individuals. Mitigating the disparate burden will require expanded financial support of tribal health care as well as increased collaboration and engagement with this marginalized population.
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Affiliation(s)
- Tyler B Kratzer
- Surveillance and Health Services Research, American Cancer Society, Kennesaw, Georgia, USA
| | - Ahmedin Jemal
- Surveillance and Health Services Research, American Cancer Society, Kennesaw, Georgia, USA
| | - Kimberly D Miller
- Surveillance and Health Services Research, American Cancer Society, Kennesaw, Georgia, USA
| | - Sarah Nash
- University of Iowa College of Public Health, Iowa City, Iowa, USA
| | - Charles Wiggins
- University of New Mexico Comprehensive Cancer Center, Albuquerque, New Mexico, USA
| | - Diana Redwood
- Alaska Native Tribal Health Consortium, Anchorage, Alaska, USA
| | - Robert Smith
- Early Cancer Detection Science, American Cancer Society, Kennesaw, Georgia, USA
| | - Rebecca L Siegel
- Surveillance and Health Services Research, American Cancer Society, Kennesaw, Georgia, USA
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27
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Jiang Y, Lin Y, Wen Y, Fu W, Wang R, He J, Zhang J, Wang Z, Ge F, Huo Z, Wang R, Peng H, Wu X, He J, Li S. Global trends in the burden of esophageal cancer, 1990-2019: results from the Global Burden of Disease Study 2019. J Thorac Dis 2023; 15:348-364. [PMID: 36910098 PMCID: PMC9992583 DOI: 10.21037/jtd-22-856] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 11/25/2022] [Indexed: 02/04/2023]
Abstract
Background Esophageal cancer is one of the leading causes of cancer death worldwide. A deeper understanding of the trends in annual incidence, mortality, and disability-adjusted life-years (DALYs) of esophageal cancer is critical for management and prevention. In this study, we report on the disease burden of esophageal cancer in 204 countries and territories between 1990 and 2019 by age, sex, and sociodemographic index (SDI). Methods Data on incidence, mortality, and DALYs were extracted from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019. The estimated numbers and age-standardized rates for esophageal cancer in 2019 are presented in this paper, as well as trends from 1990 to 2019. All estimates are presented as counts and age-standardized rates per 100,000 population, with 95% uncertainty intervals (UIs) for each estimate. Results In 2019, nearly 535,000 (95% UI: 467,000-595,000) new cases of esophageal cancer occurred globally. Esophageal cancer was responsible for more than 498,000 (95% UI: 438,000-551,000) deaths and 11.7 million (95% UI: 10.4-12.9 million) DALYs. Worldwide age-standardized rates of esophageal cancer, including incidence, deaths, and DALYs, have declined since 1990. However, the trends differ across countries and territories. Notably, there was a nonlinear but generally inverse correlation between age-standardized DALY rates and SDI. Higher age-standardized incidence and death rates were observed in males compared to females, and both increased with age. Regarding risk factors, smoking, alcohol use, and high body-mass index were 3 predominant contributors to esophageal cancer DALYs in 2019 for both sexes worldwide. Conclusions This study found a global reduction in the esophageal cancer burden, but substantial heterogeneity remains across regions and countries. Hence, the identification of high-risk groups and the exploration of specific local strategies and primary prevention efforts are required.
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Affiliation(s)
- Yu Jiang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Yuechun Lin
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Yaokai Wen
- Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, Tongji University School of Medicine, Shanghai, China
| | - Wenhai Fu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Rui Wang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Jiaxi He
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China
| | - Jianrong Zhang
- Department of General Practice and Centre for Cancer Research, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia
| | - Zhufeng Wang
- National Clinical Research Center for Respiratory Disease, State Key Laboratory of Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, China
| | - Fan Ge
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, First Clinical School, Guangzhou Medical University, Guangzhou, China
| | - Zhenyu Huo
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Runchen Wang
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Haoxin Peng
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Xiangrong Wu
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China.,Department of Clinical Medicine, Nanshan School, Guangzhou Medical University, Guangzhou, China
| | - Jianxing He
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China
| | - Shuben Li
- Department of Thoracic Surgery and Oncology, The First Affiliated Hospital of Guangzhou Medical University, China National Center for Respiratory Medicine, China State Key Laboratory of Respiratory Disease & National Clinical Research Center for Respiratory Disease, Guangzhou, China
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Sheikh M, Roshandel G, McCormack V, Malekzadeh R. Current Status and Future Prospects for Esophageal Cancer. Cancers (Basel) 2023; 15:765. [PMID: 36765722 PMCID: PMC9913274 DOI: 10.3390/cancers15030765] [Citation(s) in RCA: 102] [Impact Index Per Article: 51.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 01/10/2023] [Accepted: 01/20/2023] [Indexed: 01/28/2023] Open
Abstract
Esophageal cancer (EC) is the ninth most common cancer and the sixth leading cause of cancer deaths worldwide. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two main histological subtypes with distinct epidemiological and clinical features. While the global incidence of ESCC is declining, the incidence of EAC is increasing in many countries. Decades of epidemiologic research have identified distinct environmental exposures for ESCC and EAC subtypes. Recent advances in understanding the genomic aspects of EC have advanced our understanding of EC causes and led to using specific genomic alterations in EC tumors as biomarkers for early diagnosis, treatment, and prognosis of this cancer. Nevertheless, the prognosis of EC is still poor, with a five-year survival rate of less than 20%. Currently, there are significant challenges for early detection and secondary prevention for both ESCC and EAC subtypes, but Cytosponge™ is shifting this position for EAC. Primary prevention remains the preferred strategy for reducing the global burden of EC. In this review, we will summarize recent advances, current status, and future prospects of the studies related to epidemiology, time trends, environmental risk factors, prevention, early diagnosis, and treatment for both EC subtypes.
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Affiliation(s)
- Mahdi Sheikh
- Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Gholamreza Roshandel
- Golestan Research Center of Gastroenterology and Hepatology, Golestan University of Medical Sciences, Gorgan 49341-74515, Iran
| | - Valerie McCormack
- Environment and Lifestyle Epidemiology Branch, International Agency for Research on Cancer (IARC/WHO), 69007 Lyon, France
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 14117-13135, Iran
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Tavakoli Pirzaman A, Ebrahimzadeh Pirshahid M, Babajani B, Rahmati A, Niknezhad S, Hosseinzadeh R, Taheri M, Ebrahimi-Zadeh F, Doostmohamadian S, Kazemi S. The Role of microRNAs in Regulating Cancer Cell Response to Oxaliplatin-Containing Regimens. Technol Cancer Res Treat 2023; 22:15330338231206003. [PMID: 37849311 PMCID: PMC10586010 DOI: 10.1177/15330338231206003] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2023] [Revised: 07/18/2023] [Accepted: 10/18/2023] [Indexed: 10/19/2023] Open
Abstract
Oxaliplatin (cyclohexane-1,2-diamine; oxalate; platinum [2+]) is a third-generation chemotherapeutic drug with anticancer effects. Oxaliplatin has a role in the treatment of several cancers. It is one of the few drugs which can eliminate the neoplastic cells of colorectal cancer. Also, it has an influential role in breast cancer, lung cancer, bladder cancer, prostate cancer, and gastric cancer. Although oxaliplatin has many beneficial effects in cancer treatment, resistance to this drug is in the way to cure neoplastic cells and reduce treatment efficacy. microRNAs are a subtype of small noncoding RNAs with ∼22 nucleotides that exist among species. They have diverse roles in physiological processes, including cellular proliferation and cell death. Moreover, miRNAs have essential roles in resistance to cancer treatment and can strengthen sensitivity to chemotherapeutic drugs and regimens. In colorectal cancer, the co-treatment of oxaliplatin with anti-miR-19a can partially reverse the oxaliplatin resistance through the upregulation of phosphatase and tensin homolog (PTEN). Moreover, by preventing the spread of gastric cancer cells and downregulating glypican-3 (GPC3), MiR-4510 may modify immunosuppressive signals in the tumor microenvironment. Treatment with oxaliplatin may develop into a specialized therapeutic drug for patients with miR-4510 inhibition and glypican-3-expressing gastric cancer. Eventually, miR-122 upregulation or Wnt/β-catenin signaling suppression boosted the death of HCC cells and made them more sensitive to oxaliplatin. Herein, we have reviewed the role of microRNAs in regulating cancer cells' response to oxaliplatin, with particular attention to gastrointestinal cancers. We also discussed the role of these noncoding RNAs in the pathophysiology of oxaliplatin-induced neuropathic pain.
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Affiliation(s)
| | | | - Bahareh Babajani
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Amirhossein Rahmati
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Shokat Niknezhad
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Rezvan Hosseinzadeh
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Mehdi Taheri
- Student Research Committee, Babol University of Medical Sciences, Babol, Iran
| | - Faezeh Ebrahimi-Zadeh
- Student Research Committee, school of Medicine, Jahrom University of Medical Science, Jahrom, Iran
| | | | - Sohrab Kazemi
- Cellular and Molecular Biology Research Center, Health Research Center, Babol University of Medical Sciences, Babol, Iran
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30
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Tseng SC, Hino T, Hatabu H, Park H, Sanford NN, Lin G, Nishino M, Mamon H. Interstitial Lung Abnormalities in Patients With Locally Advanced Esophageal Cancer: Prevalence, Risk Factors, and Clinical Implications. J Comput Assist Tomogr 2022; 46:871-877. [PMID: 35995596 PMCID: PMC9675694 DOI: 10.1097/rct.0000000000001366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE Interstitial lung abnormalities (ILAs) represent nondependent abnormalities on chest computed tomography (CT) indicating lung parenchymal damages due to inflammation and fibrosis. Interstitial lung abnormalities have been studied as a predictor of clinical outcome in lung cancer, but not in other thoracic malignancies. The present study investigated the prevalence of ILA in patients with esophageal cancer and identified risk factors and clinical implications of ILA in these patients. METHODS The study included 208 patients with locally advanced esophageal cancer (median age, 65.6 years; 166 males, 42 females). Interstitial lung abnormality was scored on baseline CT scans before treatment using a 3-point scale (0 = no evidence of ILA, 1 = equivocal for ILA, 2 = ILA). Clinical characteristics and overall survival were compared in patients with ILA (score 2) and others. RESULTS An ILA was present in 14 of 208 patients (7%) with esophageal cancer on pretreatment chest CT. Patients with ILA were significantly older (median age, 69 vs 65, respectively; P = 0.011), had a higher number of pack-years of smoking ( P = 0.02), and more commonly had T4 stage disease ( P = 0.026) than patients with ILA score of 1 or 0. Interstitial lung abnormality on baseline scan was associated with a lack of surgical resection after chemoradiotherapy (7/14, 50% vs 39/194, 20% respectively; P = 0.016). Interstitial lung abnormality was not associated with overall survival (log-rank P = 0.75, Cox P = 0.613). CONCLUSIONS An ILA was present in 7% of esophageal cancer patients, which is similar to the prevalence in general population and in smokers. Interstitial lung abnormality was strongly associated with a lack of surgical resection after chemoradiotherapy, indicating an implication of ILA in treatment selection in these patients, which can be further studied in larger cohorts.
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Affiliation(s)
- Shu-Chi Tseng
- Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Takuya Hino
- Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
| | - Hiroto Hatabu
- Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
| | - Hyesun Park
- Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
| | - Nina N. Sanford
- Department of Radiation Oncology, University of Texas Southwestern
| | - Gigin Lin
- Department of Medical Imaging and Intervention, Chang Gung Memorial Hospital at Linkou and Chang Gung University, Taoyuan, Taiwan
| | - Mizuki Nishino
- Department of Radiology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
| | - Harvey Mamon
- Department of Radiation Oncology, Brigham and Women’s Hospital and Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Ave. Boston MA, 02215, USA
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Zhou R, Huang C, Luo Z, Wang T. The Association between the Risk of Esophageal Cancer and Type 2 Diabetes Mellitus: An Updated Meta-Analysis. BIOMED RESEARCH INTERNATIONAL 2022; 2022:8129771. [PMID: 36277883 PMCID: PMC9584674 DOI: 10.1155/2022/8129771] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/15/2022] [Accepted: 09/20/2022] [Indexed: 12/24/2022]
Abstract
Background A large amount of publications had reported the association between incidence of esophageal cancer (EC) and type 2 diabetes mellitus (T2DM) in the past decade. However, those papers' results are inconsistent on relationships between T2DM the incidence of EC. Therefore, the objective of this meta-analysis was to determine the relationship between T2DM and the risk of EC (including 2 histological types, esophageal adenocarcinoma [EADC] and esophageal squamous cell carcinoma [ESCC]). Method We finally extracted 19 articles though Pubmed, Embased, and Cochrane library. Those identify extraction date including 14,312 cases and 24,959,067 control records and then mixed the relative risks (RRs) and corresponding 95% confidence intervals (95%CIs) through STATA. Results We observed that there are significantly positive correlation between T2DM and EC risk (RR = 1.28, 95% CI: 1.05-1.57, P = 0.015).Also, our study showed positive correlation between T2DM and EADC (esophageal adenocarcinoma) risk (RR = 1.28, 95% CI: 1.05-1.57, P < 0.001). What's more, subgroup analysis based on ethnicity represented the Caucasian is more susceptible to EC (RR = 1.28 ,95% CI: 1.10-1.49, P = 0.001). Conclusion Those results offer a recent epidemiological and integrated evidence to ascertain the correlations between T2DM and incidence of EC. Those results take public health implications on preventing T2DM and then depress the occurrence of EC. Our study also provides referenced information for the prevention. However, some data is still insufficient, and more research should be carried out.
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Affiliation(s)
- Runquan Zhou
- Department Of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
| | - Chenglu Huang
- Department of Thoracic Surgery, Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing 400030, China
| | - Zhilin Luo
- Department Of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
| | - Tianhu Wang
- Department Of Thoracic Surgery, The Third Affiliated Hospital of Chongqing Medical University, Chongqing 401120, China
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Clinicopathological Significance of STAT3 and p-STAT3 among 91 Patients with Adenocarcinoma of the Esophagogastric Junction. DISEASE MARKERS 2022; 2022:9311684. [PMID: 36225196 PMCID: PMC9550499 DOI: 10.1155/2022/9311684] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 07/25/2022] [Accepted: 08/27/2022] [Indexed: 11/26/2022]
Abstract
Adenocarcinoma of the esophagogastric junction (AEG) has increased rapidly worldwide during the last few decades. The purpose of this study is to investigate the clinical and prognostic characteristics of signal transduction and activator of transcription factor 3(STAT3) and phosphorylated STAT3 (p-STAT3) expression in AEG patients. We retrospectively analyzed the immunohistochemical results of 61 AEG patients and followed up for 5 years, while Western blot was performed on tissues from another 30 AEG patients. The results showed that STAT3 and p-STAT3 were overexpressed in AEG tissues (P < 0.05, P < 0.01). The high expression of STAT3 was significantly associated with the pTNM stage (P < 0.05), and the increased expression of p-STAT3 was significantly associated with depth of invasion (pT), lymph node metastasis (pN), and pTNM stage (P < 0.05, P < 0.05, P < 0.05). The 5-year survival rate for AEG patients was 41.0% and was significantly associated with tumor differentiation, pN, pTNM, and p-STAT3 (P < 0.05, P < 0.01, P < 0.05, P < 0.01). Cox regression analysis confirmed that tumor differentiation, pN, and high expression of p-STAT3 were independent risk factors for the 5-year survival rate in patients with AEG (P < 0.05, P < 0.01, P < 0.05). Our study showed that STAT3 and p-STAT3 play a critical role in AEG development.
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Palmieri L, Giacomo TD, Quaresima S, Balla A, Diso D, Mottola E, Ruberto F, Paganini AM. Minimally Invasive Esophagectomy for Esophageal Cancer. GASTROINTESTINAL CANCERS 2022:111-124. [PMID: 36343154 DOI: 10.36255/exon-publications-gastrointestinal-cancers-esophagectomy] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
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Wang X, Gharahkhani P, Levine DM, Fitzgerald RC, Gockel I, Corley DA, Risch HA, Bernstein L, Chow WH, Onstad L, Shaheen NJ, Lagergren J, Hardie LJ, Wu AH, Pharoah PDP, Liu G, Anderson LA, Iyer PG, Gammon MD, Caldas C, Ye W, Barr H, Moayyedi P, Harrison R, Watson RGP, Attwood S, Chegwidden L, Love SB, MacDonald D, deCaestecker J, Prenen H, Ott K, Moebus S, Venerito M, Lang H, Mayershofer R, Knapp M, Veits L, Gerges C, Weismüller J, Reeh M, Nöthen MM, Izbicki JR, Manner H, Neuhaus H, Rösch T, Böhmer AC, Hölscher AH, Anders M, Pech O, Schumacher B, Schmidt C, Schmidt T, Noder T, Lorenz D, Vieth M, May A, Hess T, Kreuser N, Becker J, Ell C, Tomlinson I, Palles C, Jankowski JA, Whiteman DC, MacGregor S, Schumacher J, Vaughan TL, Buas MF, Dai JY. eQTL Set-Based Association Analysis Identifies Novel Susceptibility Loci for Barrett Esophagus and Esophageal Adenocarcinoma. Cancer Epidemiol Biomarkers Prev 2022; 31:1735-1745. [PMID: 35709760 PMCID: PMC9444939 DOI: 10.1158/1055-9965.epi-22-0096] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2022] [Revised: 04/13/2022] [Accepted: 06/13/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Over 20 susceptibility single-nucleotide polymorphisms (SNP) have been identified for esophageal adenocarcinoma (EAC) and its precursor, Barrett esophagus (BE), explaining a small portion of heritability. METHODS Using genetic data from 4,323 BE and 4,116 EAC patients aggregated by international consortia including the Barrett's and Esophageal Adenocarcinoma Consortium (BEACON), we conducted a comprehensive transcriptome-wide association study (TWAS) for BE/EAC, leveraging Genotype Tissue Expression (GTEx) gene-expression data from six tissue types of plausible relevance to EAC etiology: mucosa and muscularis from the esophagus, gastroesophageal (GE) junction, stomach, whole blood, and visceral adipose. Two analytical approaches were taken: standard TWAS using the predicted gene expression from local expression quantitative trait loci (eQTL), and set-based SKAT association using selected eQTLs that predict the gene expression. RESULTS Although the standard approach did not identify significant signals, the eQTL set-based approach identified eight novel associations, three of which were validated in independent external data (eQTL SNP sets for EXOC3, ZNF641, and HSP90AA1). CONCLUSIONS This study identified novel genetic susceptibility loci for EAC and BE using an eQTL set-based genetic association approach. IMPACT This study expanded the pool of genetic susceptibility loci for EAC and BE, suggesting the potential of the eQTL set-based genetic association approach as an alternative method for TWAS analysis.
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Affiliation(s)
- Xiaoyu Wang
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Puya Gharahkhani
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | - David M. Levine
- Department of Biostatistics, University of Washington, School of Public Health, Seattle, Washington, USA
| | - Rebecca C. Fitzgerald
- Medical Research Council (MRC) Cancer Unit, Hutchison-MRC Research Centre, University of Cambridge, Cambridge, UK
| | - Ines Gockel
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Douglas A. Corley
- Division of Research, Kaiser Permanente Northern California, Oakland, California, USA
- San Francisco Medical Center, Kaiser Permanente Northern California, San Francisco, California, USA
| | - Harvey A. Risch
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut, USA
| | - Leslie Bernstein
- Department of Population Sciences, Beckman Research Institute and City of Hope Comprehensive Cancer Center, Duarte, California, USA
| | - Wong-Ho Chow
- Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas, USA
| | - Lynn Onstad
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Nicholas J. Shaheen
- Division of Gastroenterology and Hepatology, University of North Carolina School of Medicine, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Jesper Lagergren
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
- School of Cancer and Pharmaceutical Sciences, King’s College London
| | | | - Anna H. Wu
- Department of Population and Public Health Sciences, University of Southern California/Norris Comprehensive Cancer Center, Los Angeles, California, USA
| | - Paul D. P. Pharoah
- Department of Oncology, University of Cambridge, Cambridge, UK
- Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
| | - Geoffrey Liu
- Pharmacogenomic Epidemiology, Ontario Cancer Institute, Toronto, Ontario, Canada
| | - Lesley A. Anderson
- Department of Epidemiology and Public Health, Queen's University of Belfast, Royal Group of Hospitals, Northern Ireland
| | - Prasad G. Iyer
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA
| | - Marilie D. Gammon
- Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USA
| | - Carlos Caldas
- Cancer Research UK, Cambridge Institute, Cambridge, UK
| | - Weimin Ye
- Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden
| | - Hugh Barr
- Department of Upper GI Surgery, Gloucestershire Royal Hospital, Gloucester, UK
| | - Paul Moayyedi
- Farncombe Family Digestive Health Research Institute, Department of Medicine, McMaster University, Hamilton, Ontario, Canada
| | - Rebecca Harrison
- Department of Pathology, Leicester Royal Infirmary, Leicester, UK
| | - RG Peter Watson
- Department of Medicine, Institute of Clinical Science, Royal Victoria Hospital, Belfast, UK
| | - Stephen Attwood
- Department of General Surgery, North Tyneside General Hospital, North Shields, UK
| | - Laura Chegwidden
- University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge, UK
| | - Sharon B. Love
- Centre for Statistics in Medicine and Oxford Clinical Trials Research Unit, Oxford, UK
| | - David MacDonald
- Department of Oral Biological and Medical Sciences, University of British Columbia, Vancouver, British Columbia, Canada
| | - John deCaestecker
- Digestive Diseases Centre, University Hospitals of Leicester, Leicester, UK
| | - Hans Prenen
- Oncology Department, University Hospital Antwerp, Edegem, Belgium
| | - Katja Ott
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
- Department of General, Visceral and Thorax Surgery, RoMed Klinikum Rosenheim, Rosenheim, Germany
| | - Susanne Moebus
- Institute for Urban Public Health, University Hospitals, University of Duisburg-Essen, Essen, Germany
| | - Marino Venerito
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg, Germany
| | - Hauke Lang
- Department of General, Visceral and Transplant Surgery, University Medical Center, University of Mainz, Mainz, Germany
| | | | - Michael Knapp
- Institute for Medical Biometry, Informatics, and Epidemiology, University of Bonn, Bonn, Germany
| | - Lothar Veits
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Christian Gerges
- Department of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany
| | | | - Matthias Reeh
- Department of General, Visceral and Thoracic Surgery, Asklepios Harzklinik Goslar, Goslar, Germany
| | - Markus M. Nöthen
- Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany
| | - Jakob R. Izbicki
- General, Visceral and Thoracic Surgery Department and Clinic. University Medical Center Hamburg-Eppendorf. Hamburg. Germany
| | - Hendrik Manner
- Department of Internal Medicine II, Frankfurt Hoechst Hospital, Frankfurt, Germany
| | - Horst Neuhaus
- Department of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany
| | - Thomas Rösch
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Anne C. Böhmer
- Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany
| | - Arnulf H. Hölscher
- Clinic for General, Visceral and Trauma Surgery, Contilia Center for Esophageal Diseases. Elisabeth Hospital Essen, Germany
| | - Mario Anders
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
- Department of Gastroenterology and Interdisciplinary Endoscopy, Vivantes Wenckebach-Klinikum, Berlin, Germany
| | - Oliver Pech
- Department of Gastroenterology and Interventional Endoscopy, St. John of God Hospital, Regensburg, Germany
| | - Brigitte Schumacher
- Department of Internal Medicine, Evangelisches Krankenhaus, Düsseldorf, Germany
- Department of Internal Medicine and Gastroenterology, Elisabeth Hospital, Essen, Germany
| | - Claudia Schmidt
- Department of General, Visceral and Cancer Surgery, University of Cologne, Cologne, Germany
| | - Thomas Schmidt
- Department of General, Visceral and Transplantation Surgery, University of Heidelberg, Heidelberg, Germany
| | - Tania Noder
- Department of Interdisciplinary Endoscopy, University Hospital Hamburg-Eppendorf, Hamburg, Germany
| | - Dietmar Lorenz
- Department of General and Visceral Surgery, Sana Klinikum, Offenbach, Germany
| | - Michael Vieth
- Institute of Pathology, Friedrich-Alexander-University Erlangen-Nuremberg, Klinikum Bayreuth, Bayreuth, Germany
| | - Andrea May
- Department of Gastroenterology, Oncology and Pneumology, Asklepios Paulinen Klinik, Wiesbaden, Germany
| | - Timo Hess
- Center for Human Genetics, University Hospital of Marburg, Marburg, Germany
| | - Nicole Kreuser
- Department of Visceral, Transplant, Thoracic and Vascular Surgery, University Hospital of Leipzig, Leipzig, Germany
| | - Jessica Becker
- Institute of Human Genetics, Medical Faculty, University of Bonn, Bonn, Germany
| | - Christian Ell
- Department of Medicine II, Sana Klinikum, Offenbach, Germany
| | - Ian Tomlinson
- Edinburgh Cancer Research Centre, IGMM, University of Edinburgh, UK
| | - Claire Palles
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | | | - David C. Whiteman
- Cancer Control, QIMR Berghofer Medical Research Institute, Brisbane, Australia
| | - Stuart MacGregor
- QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia
| | | | - Thomas L. Vaughan
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Epidemiology, University of Washington, School of Public Health, Seattle, Washington, USA
| | - Matthew F. Buas
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14263 USA
| | - James Y. Dai
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
- Department of Biostatistics, University of Washington, School of Public Health, Seattle, Washington, USA
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Zhang N, Wang D, Hu X, Zhang G, Li Z, Zhao Y, Liu Z, Wang Y. Analysis of immune status in gastric adenocarcinoma with different infiltrating patterns and origin sites. Front Immunol 2022; 13:978715. [PMID: 36081505 PMCID: PMC9445833 DOI: 10.3389/fimmu.2022.978715] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 07/27/2022] [Indexed: 12/03/2022] Open
Abstract
Tumor infiltration pattern (INF) and tumor origin site were reported to significantly affect the prognosis of gastric cancer (GC), while the immune status under these contexts is not clear. In this study, we correlated the density and phenotype of tumor-infiltrating lymphocytes (TILs) with INF and the tumor origin site to reflect the biological behavior of tumors from a new perspective and also determined their effects on overall survival (OS) and other related clinicopathological features in archival samples of 147 gastric cancers with 10-year follow-up data. We found that the INFc growth pattern (an invasive growth without a distinct border) of GC lacked immune cell infiltration, particularly the cytotoxic T cells and their activated form. It is also significantly associated with an unfavorable prognosis (P < 0.001) and proximal site (P = 0.001), positive lymph node metastasis (P = 0.002), and later tumor-node-metastasis stage (P < 0.001). Moreover, the density and sub-type of TILs infiltration were significantly different in disparate differentiated areas for the tumor tissue with INFb. Compared with distal gastric cancer, proximal gastric cancers were prone to grow in an INFc pattern (P = 0.001) and infiltrated with fewer TILs, experiencing a shorter survival time (P = 0.013). Multivariate analysis showed that only the INF and the density of TILs were demonstrated to be the independent prognostic factors of OS for the GC. We concluded that GC with an aggressive growth pattern arising from proximal sites always had a weak immune response and resulted in a poor prognosis. The interaction between them and their synergistic or antagonistic effects in the development of tumors need to be further studied. This study opens up a new perspective for research on the biological behavior of the tumor.
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Affiliation(s)
- Nana Zhang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi’an Jiaotong University, Xian, China
| | - Depu Wang
- Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi’an Jiaotong University, Xian, China
- Department of Science and Technology, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, China
| | - Xiaoyan Hu
- Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi’an Jiaotong University, Xian, China
| | - Guanjun Zhang
- Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi’an Jiaotong University, Xian, China
- Department of Pathology, The First Affiliated Hospital of Xi’an Jiaotong University, Xian, China
| | - Zhuoqun Li
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yan Zhao
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Zhijun Liu
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
| | - Yili Wang
- Institute of Regenerative and Reconstructive Medicine, Med-X Institute, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China
- Institute for Cancer Research, School of Basic Medical Science, Health Science Center of Xi’an Jiaotong University, Xian, China
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36
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Abstract
Oesophageal adenocarcinoma (OAC) develops from columnar metaplasia of the distal oesophagus, Barrett's oesophagus (BO), secondary to chronic gastro-oesophageal reflux disease (GORD). In the present review, the stepwise development of GORD, BO and OAC is presented and the evidence of OAC prevention, including treatment with proton pump inhibitors (PPIs). PPIs are the main treatment of GORD and BO, with some evidence of prevention of OAC in these patients. However, as about 40% of OAC patient do not report a history of GORD and fewer than 15% of OAC cases are detected in individuals during BO surveillance, prevention of OAC is limited by PPI use in GORD and BO patients.
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Affiliation(s)
- Eivind Ness-Jensen
- HUNT Research Centre, Department of Public Health and Nursing, NTNU, Norwegian University of Science and Technology, Levanger, Norway.,Department of Medicine, Levanger Hospital, Nord-Trøndelag Hospital Trust, Levanger, Norway.,Upper Gastrointestinal Surgery, Department of Molecular Medicine and Surgery, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden
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37
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Uthansingh K, Parida PK, Pati GK, Sahu MK, Padhy RN. Evaluating the Association of Genetic Polymorphism of Cytochrome p450 (CYP2C9*3) in Gastric Cancer Using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP). Cureus 2022; 14:e27220. [PMID: 36035062 PMCID: PMC9399687 DOI: 10.7759/cureus.27220] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/25/2022] [Indexed: 11/05/2022] Open
Abstract
Background and aim As a distinguished system, the cytochrome P450 (CYP) enzyme superfamily is involved in the biotransformation of several endogenous and exogenous substances including drugs, toxins, and carcinogens. Reports on the role of CYP enzyme in gastric cancer (GC) from the Eastern region of India are scarce. The present study aimed to evaluate the effect of single nucleotide polymorphisms (SNP) in cytochrome P450 family 2 subfamily C member 9 (CYP2C9*3) among cases with gastric malignancy. Material and methods The current study is a cross-sectional observational study carried out among 113 GC cases attending the Institute of Medical Sciences and SUM Hospital, Bhubaneswar, India, and Srirama Chandra Bhanja Medical College and Hospital, Cuttack, India. Two ml of venous blood was collected from the confirmed cases of GC. The samples were subjected to genomic DNA isolation followed by polymerase chain reaction (PCR) and restriction fragment length polymorphism (PCR-RFLP). Results The prevalence of both homozygous and heterozygous mutation in GC cases is 4% and 8%, respectively. The overall association of cytochrome P450 family 2 subfamily C member 9 (CYP2C9) mutation in GC cases is 12% whereas 88% were detected as wild/standard type. The mutation CYP2C9 SNP has been seen in Helicobacter pylori-infected cases and as well as those without H. pylori infection. Conclusions The CYP2C9*3 genetic polymorphism might play a significant role as a risk factor for the development of gastric malignancy irrespective of H. pylori infection, among the eastern Indian population.
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38
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Ali MW, Chen J, Yan L, Wang X, Dai JY, Vaughan TL, Casey G, Buas MF. A risk variant for Barrett's esophagus and esophageal adenocarcinoma at chr8p23.1 affects enhancer activity and implicates multiple gene targets. Hum Mol Genet 2022; 31:3975-3986. [PMID: 35766871 DOI: 10.1093/hmg/ddac141] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/09/2022] [Accepted: 06/16/2022] [Indexed: 11/12/2022] Open
Abstract
Nineteen genetic susceptibility loci for esophageal adenocarcinoma (EAC) and its precursor Barrett's esophagus (BE) have been identified through genome-wide association studies (GWAS). Clinical translation of such discoveries, however, has been hindered by the slow pace of discovery of functional/causal variants and gene targets at these loci. We previously developed a systematic informatics pipeline to prioritize candidate functional variants using functional potential scores, applied the pipeline to select high-scoring BE/EAC risk loci, and validated a functional variant at chr19p13.11 (rs10423674). Here, we selected two additional prioritized loci for experimental interrogation: chr3p13/rs1522552 and chr8p23.1/rs55896564. Candidate enhancer regions encompassing these variants were evaluated using luciferase reporter assays in two EAC cell lines. One of the two regions tested exhibited allele-specific enhancer activity - 8p23.1/rs55896564. CRISPR-mediated deletion of the putative enhancer in EAC cell lines correlated with reduced expression of three candidate gene targets: B lymphocyte kinase (BLK), nei like DNA glycosylase 2 (NEIL2), and cathepsin B (CTSB). Expression quantitative trait locus (eQTL) mapping in normal esophagus and stomach revealed strong associations between the BE/EAC risk allele at rs55896564 (G) and lower expression of CTSB, a protease gene implicated in epithelial wound repair. These results further support the utility of functional potential scores for GWAS variant prioritization, and provide the first experimental evidence of a functional variant and risk enhancer at the 8p23.1 GWAS locus. Identification of CTSB, BLK, and NEIL2 as candidate gene targets suggests that altered expression of these genes may underlie the genetic risk association at 8p23.1 with BE/EAC.
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Affiliation(s)
- Mourad Wagdy Ali
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Jianhong Chen
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Li Yan
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
| | - Xiaoyu Wang
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - James Y Dai
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA
| | - Thomas L Vaughan
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.,Department of Epidemiology, University of Washington, School of Public Health, Seattle, Washington, USA
| | - Graham Casey
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA
| | - Matthew F Buas
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
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39
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Koike T, Saito M, Ohara Y, Hatta W, Masamune A. Current status of surveillance for Barrett's esophagus in Japan and the West. DEN OPEN 2022; 2:e94. [PMID: 35898591 PMCID: PMC9302351 DOI: 10.1002/deo2.94] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/30/2021] [Revised: 01/08/2022] [Accepted: 01/12/2022] [Indexed: 11/06/2022]
Abstract
Prospective studies in western countries have shown that the obvious risk factors for Barrett's esophageal cancer are male sex, smoking habit, a longer length of Barrett's esophagus, and low‐grade dysplasia. However, few reports have prospectively examined risk factors for adenocarcinoma development from Barrett's esophagus in Japan. In the West, where adenocarcinoma is common among esophageal cancer, endoscopic surveillance of Barrett's esophagus every 2–5 years is recommended for early detection of adenocarcinoma. However, there is no established surveillance method in Japan. In recent years, the incidence of adenocarcinoma from long‐segment Barrett's esophagus and short‐segment Barrett's esophagus longer than 2 cm in Japan has been reported to be similar to the West. For surveillance of adenocarcinoma arising from Barrett's esophagus, recognizing the characteristics of superficial adenocarcinoma and carefully observing the entire Barrett's esophagus are needed. It has been reported that representative characteristics of Barrett's adenocarcinoma are a reddish area or a lesion located on the anterior to the right sidewall. It is necessary to establish surveillance methods for Barrett's esophagus sooner in Japan.
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Affiliation(s)
- Tomoyuki Koike
- Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi Japan
| | - Masahiro Saito
- Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi Japan
| | - Yuki Ohara
- Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi Japan
| | - Waku Hatta
- Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi Japan
| | - Atsushi Masamune
- Division of Gastroenterology Tohoku University Graduate School of Medicine Miyagi Japan
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40
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Schmidt M, Hackett RJ, Baker AM, McDonald SAC, Quante M, Graham TA. Evolutionary dynamics in Barrett oesophagus: implications for surveillance, risk stratification and therapy. Nat Rev Gastroenterol Hepatol 2022; 19:95-111. [PMID: 34728819 DOI: 10.1038/s41575-021-00531-4] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/24/2021] [Indexed: 12/13/2022]
Abstract
Cancer development is a dynamic evolutionary process characterized by marked intratumoural heterogeneity at the genetic, epigenetic and phenotypic levels. Barrett oesophagus, the pre-malignant condition to oesophageal adenocarcinoma (EAC), is an exemplary system to longitudinally study the evolution of malignancy. Evidence has emerged of Barrett oesophagus lesions pre-programmed for progression to EAC many years before clinical detection, indicating a considerable window for therapeutic intervention. In this Review, we explore the mechanisms underlying clonal expansion and contraction that establish the Barrett oesophagus clonal mosaicism over time and space and discuss intrinsic genotypic and extrinsic environmental drivers that direct the evolutionary trajectory of Barrett oesophagus towards a malignant phenotype. We propose that understanding and exploiting the evolutionary dynamics of Barrett oesophagus will identify novel therapeutic targets, improve prognostic tools and offer the opportunity for personalized surveillance programmes geared to prevent progression to EAC.
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Affiliation(s)
- Melissa Schmidt
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
| | - Richard J Hackett
- Clonal Dynamics in Epithelia Group; Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Ann-Marie Baker
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Stuart A C McDonald
- Clonal Dynamics in Epithelia Group; Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
| | - Michael Quante
- Department of Medicine II, Klinikum rechts der Isar, Technical University Munich (TUM), München, Germany
- Department of Medicine II, Universitaetsklinikum Freiburg, Freiburg, Germany
| | - Trevor A Graham
- Evolution and Cancer Laboratory, Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
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41
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Wang G, Pan C, Cao K, Zhang J, Geng H, Wu K, Wen J, Liu C. Impacts of Cigarette Smoking on the Tumor Immune Microenvironment in Esophageal Squamous Cell Carcinoma. J Cancer 2022; 13:413-425. [PMID: 35069891 PMCID: PMC8771511 DOI: 10.7150/jca.65400] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 11/23/2021] [Indexed: 02/05/2023] Open
Abstract
Objective: Cigarette smoking is a carcinogenic factor for esophageal cancer and evidence also indicates its effects on tumor microenvironment in patients with esophageal squamous cell carcinoma (ESCC). Materials and Methods: In our study, we demonstrated nine immune infiltrating cells and markers in non-smokers and smokers of 189 non-drinking ESCC patients with multiplex fluorescent immunohistochemistry (mflHC) staining and multispectral imaging. The impacts of cigarette smoking on tumor microenvironment and patient prognosis were also analyzed. Results: Among 189 ESCC patients of non-drinker, 86 patients was current smokers, while 34 males and 59 females were non-smokers and 10 former-smokers. Among 34 male non-smokers and 83 smokers, distinct immune infiltrating cells, with increased DCs in stromal regions (P=0.033), elevated infiltration of Treg cells in intraepithelial regions (P=0.010) and reduced activate cytotoxic T lymphocytes (aCTLs) in both intraepithelial (P=0.021) and stromal regions (P=0.017), were observed in tumor specimens of smoking males, implying an immune suppressed response during cigarette smoke exposure. For smoking characters, the level of stromal tumor-associated macrophages (TAMs) infiltration was correlated with smoking year after age adjusted (rs =0.352, P=0.002). Though cigarette smoking did not alter the expression of programmed death ligand 1 (PD-L1) in epithelial cells or TAMs in tumor specimens, higher expression of PD-L1 predicted a worse survival in non-smokers but not smokers. Conclusions: Our findings indicated smoking may impair T cell-mediated immune response and supported the possible impacts of cigarette smoking in PD-L1 related research and therapy of ESCC.
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Affiliation(s)
- Geng Wang
- Department of Thoracic Surgery, Cancer Hospital of Shantou University Medical College, Shantou, Guangdong, China
| | - Chuqing Pan
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
| | - Kexin Cao
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China
| | - Jingbing Zhang
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China
| | - Hui Geng
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China
| | - Kusheng Wu
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China
| | - Jing Wen
- State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, China
- Guangdong Esophageal Cancer Research Institute, Guangzhou, China
| | - Caixia Liu
- Department of Preventive Medicine, Shantou University Medical College, Shantou, Guangdong, China
- Department of Preventive Medicine, Shantou University Medical College, No.22, Xinling Road. Shantou 515041, Guangdong, People's Republic of China
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42
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Yang Y, Xu Y, Zhao C, Zhang L, Nuerbol A, Wang L, Jiao Y. Pronounced Enhancement in Radiosensitization of Esophagus Cancer Cultivated in Docosahexaenoic Acid via the PPAR -γ Activation. Front Med (Lausanne) 2022; 9:922228. [PMID: 37153924 PMCID: PMC10155814 DOI: 10.3389/fmed.2022.922228] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/17/2022] [Accepted: 06/22/2022] [Indexed: 05/10/2023] Open
Abstract
Docosahexaenoic acid (DHA) has been reported to suppress the tumor growth and improve prognosis and has been used to cooperate with many other chemotherapy medicines. Up to now, surveys focused on the Interaction between DHA and radiation are relatively modest. Our study sought to evaluate the radiosensitivity changes caused by DHA on esophageal cancer cells. We selected TE-1 and TE-10 esophagus cancer cells as models and performed routine cell proliferation assay and cloning assay to detect the impact of DHA combined with X-ray. We used cell cycle assay, lipid peroxidation assay, comet assay, and apoptosis assay to unearth the potential causes. We also launched a mouse transplanted tumor experiment to verify the synergetic effect of DHA and irradiation. Finally, a western blot assay was used to find a novel mechanism. As a result, DHA improved TE-1 and TE-10 radiosensitivity in vivo and in vitro. What's more, PPAR-γ expression increased due to the DHA supplement. Inhibiting PPAR-γ could attenuate benefits brought out by DHA somehow. Due to its explicit usage and convenience, DHA would serve as an adjuvant therapy before radiotherapy if the clinical trials indicated positive.
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Affiliation(s)
- Ying Yang
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Ying Xu
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Congzhao Zhao
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Lirong Zhang
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
| | - Aslibek Nuerbol
- Department of Ultrasound Diagnosis, Gaochun Peoples' Hospital, Affiliated Hospital of Nanjing Drum Tower Hospital, Nanjing, China
| | - Lili Wang
- Department of Radiotherapy, Second Hospital of Soochow University, Suzhou, China
| | - Yang Jiao
- State Key Laboratory of Radiation Medicine and Protection, School of Radiation Medicine and Protection, Soochow University, Suzhou, China
- *Correspondence: Yang Jiao
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43
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Karakasheva TA, Gabre JT, Sachdeva UM, Cruz-Acuña R, Lin EW, DeMarshall M, Falk GW, Ginsberg GG, Yang Z, Kim MM, Diffenderfer ES, Pitarresi JR, Li J, Muir AB, Hamilton KE, Nakagawa H, Bass AJ, Rustgi AK. Patient-derived organoids as a platform for modeling a patient's response to chemoradiotherapy in esophageal cancer. Sci Rep 2021; 11:21304. [PMID: 34716381 PMCID: PMC8556341 DOI: 10.1038/s41598-021-00706-8] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2021] [Accepted: 10/08/2021] [Indexed: 12/12/2022] Open
Abstract
3D patient-derived organoids (PDOs) have been utilized to evaluate potential therapies for patients with different cancers. However, the use of PDOs created from treatment-naive patient biopsies for prediction of clinical outcomes in patients with esophageal cancer has not yet been reported. Herein we describe a pilot prospective observational study with the goal of determining whether esophageal cancer PDOs created from treatment naive patients can model or predict clinical outcomes. Endoscopic biopsies of treatment-naive patients at a single tertiary care center were used to generate esophageal cancer PDOs, which were treated with standard-of-care chemotherapy, gamma-irradiation, and newer non-standard approaches, such as proton beam therapy or two small molecule inhibitors. Clinical outcomes of patients following neoadjuvant treatment were compared to their in vitro PDO responses, demonstrating the PDO's ability to mirror clinical response, suggesting the value of PDOs in prediction of clinical response to new therapeutic approaches. Future prospective clinical trials should test the use of pre-treatment PDOs to identify specific, targeted therapies for individual patients with esophageal adenocarcinoma.
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Affiliation(s)
- Tatiana A Karakasheva
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Joel T Gabre
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA
| | - Uma M Sachdeva
- Division of Thoracic Surgery, Massachusetts General Hospital, Boston, MA, USA
| | - Ricardo Cruz-Acuña
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Eric W Lin
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.,Massachusetts General Hospital, Boston, MA, USA
| | - Maureen DeMarshall
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Gary W Falk
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Gregory G Ginsberg
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Zhaohai Yang
- Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Michele M Kim
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Eric S Diffenderfer
- Department of Radiation Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jason R Pitarresi
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Jinyang Li
- Division of Gastroenterology, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Amanda B Muir
- Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Kathryn E Hamilton
- Gastrointestinal Epithelium Modeling Program, Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital of Philadelphia, Philadelphia, PA, USA
| | - Hiroshi Nakagawa
- Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA
| | - Adam J Bass
- Dana-Farber Cancer Institute, Harvard Medical School, Broad Institute, Boston, MA, USA.,Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, New York, NY, USA
| | - Anil K Rustgi
- Division of Digestive and Liver Diseases, Department of Medicine and Herbert Irving Comprehensive Cancer Research Center, Columbia University Irving Medical Center, 1130 St. Nicholas Avenue, Suite 201, New York, NY, 10032, USA.
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Nucci D, Marino A, Realdon S, Nardi M, Fatigoni C, Gianfredi V. Lifestyle, WCRF/AICR Recommendations, and Esophageal Adenocarcinoma Risk: A Systematic Review of the Literature. Nutrients 2021; 13:3525. [PMID: 34684526 PMCID: PMC8538904 DOI: 10.3390/nu13103525] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/30/2021] [Accepted: 10/05/2021] [Indexed: 12/12/2022] Open
Abstract
One of the most notable changes in the epidemiology of esophageal cancer (EC) is the rising incidence and prevalence of esophageal adenocarcinoma (EAC) in developed countries. The aim of this systematic review was to collect and summarize all the available evidence regarding lifestyle, diet, and EAC risk. We searched the PubMed and Scopus databases in January 2021 for studies providing information about lifestyle, diet, WCRF/AICR recommendations, and EAC risk; published in English; without a time filter. The Newcastle-Ottawa Scale was used to assess risk of bias. The results are stratified by risk factor. A total of 106 publications were included. Half of the case-control studies were judged as high quality, whilst practically all cohort studies were judged as high quality. Body mass index and waist circumference were associated with increased EAC risk. Physical activity did not appear to have a significant direct role in EAC risk. A diet rich in fruit, vegetables, and whole grains appeared to be more protective than a Western diet. Alcohol does not seem to be related to EAC, whereas smokers, particularly heavy smokers, have an increased risk of EAC. Prevention remains the best option to avert EAC. Comprehensible and easy to follow recommendations should be provided to all subjects. Protocol ID number: CRD-42021228762, no funds received.
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Affiliation(s)
- Daniele Nucci
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Alessio Marino
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy
| | - Stefano Realdon
- Digestive Endoscopy Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Mariateresa Nardi
- Nutritional Support Unit, Veneto Institute of Oncology IOV-IRCCS, Via Gattamelata 64, 35128 Padua, Italy
| | - Cristina Fatigoni
- Department of Pharmaceutical Science, University of Perugia, Via del Giochetto 2, 06123 Perugia, Italy
| | - Vincenza Gianfredi
- School of Medicine, Vita-Salute San Raffaele University, Via Olgettina, 60, 20132 Milan, Italy
- CAPHRI Care and Public Health Research Institute, Maastricht University, 6211 Maastricht, The Netherlands
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45
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Becskeházi E, Korsós MM, Gál E, Tiszlavicz L, Hoyk Z, Deli MA, Köhler ZM, Keller-Pintér A, Horváth A, Csekő K, Helyes Z, Hegyi P, Venglovecz V. Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett's Esophageal Cell Line. Int J Mol Sci 2021; 22:10581. [PMID: 34638919 PMCID: PMC8509038 DOI: 10.3390/ijms221910581] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 09/27/2021] [Accepted: 09/27/2021] [Indexed: 01/22/2023] Open
Abstract
Several clinical studies indicate that smoking predisposes its consumers to esophageal inflammatory and malignant diseases, but the cellular mechanism is not clear. Ion transporters protect esophageal epithelial cells by maintaining intracellular pH at normal levels. In this study, we hypothesized that smoking affects the function of ion transporters, thus playing a role in the development of smoking-induced esophageal diseases. Esophageal cell lines were treated with cigarettesmoke extract (CSE), and the viability and proliferation of the cells, as well as the activity, mRNA and protein expression of the Na+/H+ exchanger-1 (NHE-1), were studied. NHE-1 expression was also investigated in human samples. For chronic treatment, guinea pigs were exposed to tobacco smoke, and NHE-1 activity was measured. Silencing of NHE-1 was performed by using specific siRNA. CSE treatment increased the activity and protein expression of NHE-1 in the metaplastic cells and decreased the rate of proliferation in a NHE-1-dependent manner. In contrast, CSE increased the proliferation of dysplastic cells independently of NHE-1. In the normal cells, the expression and activity of NHE-1 decreased due to in vitro and in vivo smoke exposure. Smoking enhances the function of NHE-1 in Barrett's esophagus, and this is presumably a compensatory mechanism against this toxic agent.
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Affiliation(s)
- Eszter Becskeházi
- Department of Pharmacology and Pharmacotherapy, University of Szeged, H-6721 Szeged, Hungary; (E.B.); (M.M.K.); (E.G.)
| | - Marietta Margaréta Korsós
- Department of Pharmacology and Pharmacotherapy, University of Szeged, H-6721 Szeged, Hungary; (E.B.); (M.M.K.); (E.G.)
| | - Eleonóra Gál
- Department of Pharmacology and Pharmacotherapy, University of Szeged, H-6721 Szeged, Hungary; (E.B.); (M.M.K.); (E.G.)
| | - László Tiszlavicz
- Department of Pathology, University of Szeged, H-6725 Szeged, Hungary;
| | - Zsófia Hoyk
- Biological Research Centre, Institute of Biophysics, H-6726 Szeged, Hungary; (Z.H.); (M.A.D.)
| | - Mária A. Deli
- Biological Research Centre, Institute of Biophysics, H-6726 Szeged, Hungary; (Z.H.); (M.A.D.)
| | - Zoltán Márton Köhler
- Department of Biochemistry, University of Szeged, H-6720 Szeged, Hungary; (Z.M.K.); (A.K.-P.)
| | - Anikó Keller-Pintér
- Department of Biochemistry, University of Szeged, H-6720 Szeged, Hungary; (Z.M.K.); (A.K.-P.)
| | - Attila Horváth
- Department of Pharmacognosy, University of Szeged, H-6720 Szeged, Hungary;
| | - Kata Csekő
- Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; (K.C.); (Z.H.)
- PharmInVivo Ltd., H-7629 Pécs, Hungary
| | - Zsuzsanna Helyes
- Department of Pharmacology and Pharmacotherapy, Medical School & Szentágothai Research Centre, University of Pécs, H-7624 Pécs, Hungary; (K.C.); (Z.H.)
- PharmInVivo Ltd., H-7629 Pécs, Hungary
| | - Péter Hegyi
- First Department of Medicine, University of Szeged, H-6720 Szeged, Hungary;
- Medical School & Szentágothai Research Centre, Institute for Translational Medicine, University of Pécs, H-7624 Pécs, Hungary
- Division of Gastroenterology, First Department of Medicine, Medical School, University of Pécs, H-7624 Pécs, Hungary
| | - Viktória Venglovecz
- Department of Pharmacology and Pharmacotherapy, University of Szeged, H-6721 Szeged, Hungary; (E.B.); (M.M.K.); (E.G.)
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Kröner PT, Cortés P, Lukens FJ. The Medical Management of Gastroesophageal Reflux Disease: A Narrative Review. J Prim Care Community Health 2021; 12:21501327211046736. [PMID: 34581222 PMCID: PMC8481709 DOI: 10.1177/21501327211046736] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE The medical management of gastroesophageal reflux disease (GERD) continues to evolve. Our aim was to systematically assess the literature to provide an updated review of the evidence on lifestyle modifications and pharmacological therapy for the management of GERD. BACKGROUND The cornerstones of GERD medical management consist of lifestyle modifications and pharmacologic agents. Most recently, evidence has emerged linking anti-reflux pharmacologic therapy to adverse events, such as kidney injury, metabolic bone disease, myocardial infarction, and even dementia, among others. METHODS A systematic search of the databases of PubMed/MEDLINE, Embase, and Cochrane Library was performed for articles on the medical management of GERD between inception and March 1, 2021. CONCLUSION Although pharmacological therapy has been associated with potential adverse events, further research is needed to determine if this association exists. For this reason, lifestyle modifications should be considered first-line, while pharmacologic therapy can be considered in patients in whom lifestyle modifications have proven to be ineffective in controlling their symptoms or cannot institute them. Naturally, extra-esophageal causes for GERD-like symptoms must be considered on suspected high-risk patients and excluded before considering treatment for GERD.
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Clinical and Lifestyle-Related Prognostic Indicators among Esophageal Adenocarcinoma Patients Receiving Treatment at a Comprehensive Cancer Center. Cancers (Basel) 2021; 13:cancers13184653. [PMID: 34572881 PMCID: PMC8465866 DOI: 10.3390/cancers13184653] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 09/13/2021] [Accepted: 09/13/2021] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Esophageal adenocarcinoma (EAC) is a highly lethal cancer with rising incidence in Western countries. Despite diagnostic and therapeutic advances, average 5-year EAC survival remains poor (~20%), with tumor stage and treatment the strongest prognostic factors. The role of lifestyle-related exposures remains uncertain. To address this gap, we analyzed survival associations among EAC patients treated at a tertiary cancer center. Importantly, this study is among the first to assess survival relationships by disease stage for several key lifestyle-related exposures (e.g., physical activity, medications, and diet), enabling us to identify associations which may have been obscured in past analyses. Our findings suggest that lifestyle interventions such as smoking cessation, exercise regimens, and use of cholesterol-lowering (statin) or anti-inflammatory (NSAID) medications may represent promising avenues to improve outcomes in this deadly cancer. Abstract Purpose: The incidence of esophageal adenocarcinoma (EAC) has risen substantially in recent decades, while the average 5-year survival remains only ~20%. Disease stage and treatment are the strongest prognostic factors. The role of lifestyle factors in relation to survival remains uncertain, with a handful of studies to date investigating associations with obesity, smoking, physical activity, diet, or medications. Methods: This study included patients diagnosed with primary adenocarcinoma of the esophagus, gastroesophageal junction, or cardia (N = 371) at Roswell Park Comprehensive Cancer Center between 2003 and 2019. Leveraging extensive data abstracted from electronic medical records, epidemiologic questionnaires, and a tumor registry, we analyzed clinical, behavioral, and environmental exposures and evaluated stage-specific associations with survival. Survival distributions were visualized using Kaplan–Meier curves. Cox proportional hazards regression models adjusted for age, sex, stage, treatment, and comorbidities were used to estimate the association between each exposure and all-cause or cancer-specific mortality. Results: Among patients presenting with localized/regional tumors (stages I–III), current smoking was associated with increased overall mortality risk (HR = 2.5 [1.42–4.53], p = 0.002), while current physical activity was linked to reduced risk (HR = 0.58 [0.35–0.96], p = 0.035). Among patients with stage IV disease, individuals reporting pre-diagnostic use of statins (HR = 0.62 [0.42–0.92], p = 0.018) or NSAIDs (HR = 0.61 [0.42–0.91], p = 0.016) had improved overall survival. Exploratory analyses suggested that high pre-diagnostic dietary consumption of broccoli, carrots, and fiber correlated with prolonged overall survival in patients with localized/regional disease. Conclusion: Our data suggest that lifestyle exposures may be differentially associated with EAC survival based on disease stage. Future investigation of larger, diverse patient cohorts is essential to validate these findings. Our results may help inform the development of lifestyle-based interventions to improve EAC prognosis and quality of life.
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Huang H, Fang W, Lin Y, Zheng Z, Wang Z, Chen X, Yu K, Lu G. Predictive Model for Overall Survival and Cancer-Specific Survival in Patients with Esophageal Adenocarcinoma. JOURNAL OF ONCOLOGY 2021; 2021:4138575. [PMID: 34567114 PMCID: PMC8457966 DOI: 10.1155/2021/4138575] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Accepted: 09/01/2021] [Indexed: 12/16/2022]
Abstract
OBJECTIVE Recent years, there has been a rapid increase in the incidence of esophageal adenocarcinoma (EAC), while the prognosis for patients diagnosed remains poor and has slightly improved. METHODS We extracted 6,466 cases with detailed demographical characteristics including age at diagnosis, sex, ethnicity, marital status, and clinical features, involving tumor grade and stage at diagnosis and treatment modalities (radiation therapy, chemotherapy, and surgery) from the Surveillance, Epidemiology, and End Results (SEER) (1975-2017) dataset. They were further randomly divided into the training and validating cohorts. Univariate and multivariate Cox analyses were conducted to determine significant variables for construction of nomogram. The predictive power of the model was then assessed by Harrell concordance index (C-index) and the area under the curve (AUC) of the receiver operating characteristic (ROC) curve. RESULTS Multivariate analysis revealed that age, marital status, insurance, tumor grade, TNM stage, surgery, and chemotherapy all showed a significant association with overall survival (OS) and cancer-specific survival (CSS). These characteristics were employed to build a nomogram. Particularly, the discrimination of nomogram for OS and CSS prediction in the training set were excellent (C-index = 0.762, 95% CI: 0.754-0.770 and C-index = 0.774, 95% CI: 0.766-0.782). The AUC of the nomogram for predicting 2- and 5-year OS was 0.834 and 0.853 and CSS was 0.844 and 0.866. Similar results were observed in the internal validation set. CONCLUSION We have successfully established a novel nomogram for predicting OS and CSS in EAC patients with good accuracy, which can help clinicians predict the survival of individual patient survival and provide optimal treatment strategies.
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Affiliation(s)
- He Huang
- Department of Hematology and Oncology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Weiyue Fang
- Department of Hematology and Oncology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Ying Lin
- Department of Hematology and Oncology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | | | - Zefan Wang
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiangfen Chen
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Kang Yu
- Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China
| | - Guangrong Lu
- Department of Gastroenterology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, China
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Chen J, Ali MW, Yan L, Dighe SG, Dai JY, Vaughan TL, Casey G, Buas MF. Prioritization and functional analysis of GWAS risk loci for Barrett's esophagus and esophageal adenocarcinoma. Hum Mol Genet 2021; 31:410-422. [PMID: 34505128 DOI: 10.1093/hmg/ddab259] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 08/17/2021] [Accepted: 08/30/2021] [Indexed: 01/03/2023] Open
Abstract
Genome-wide association studies (GWAS) have identified ~ 20 genetic susceptibility loci for esophageal adenocarcinoma (EAC), and its precursor, Barrett's esophagus (BE). Despite such advances, functional/causal variants and gene targets at these loci remain undefined, hindering clinical translation. A key challenge is that most causal variants map to non-coding regulatory regions such as enhancers, and typically, numerous potential candidate variants at GWAS loci require testing. We developed a systematic informatics pipeline for prioritizing candidate functional variants via integrative functional potential scores consolidated from multi-omics annotations, and used this pipeline to identify two high-scoring variants for experimental interrogation: chr9q22.32/rs11789015 and chr19p13.11/rs10423674. Minimal candidate enhancer regions spanning these variants were evaluated using luciferase reporter assays in two EAC cell lines. One of the two variants tested (rs10423674) exhibited allele-specific enhancer activity. CRISPR-mediated deletion of the putative enhancer region in EAC cell lines correlated with reduced expression of two genes-CREB-regulated transcription coactivator 1 (CRTC1) and Cartilage oligomeric matrix protein (COMP); expression of five other genes remained unchanged (CRLF1, KLHL26, TMEM59L, UBA52, RFXANK). Expression quantitative trait locus (eQTL) mapping indicated that rs10423674 genotype correlated with CRTC1 and COMP expression in normal esophagus. This study represents the first experimental effort to bridge GWAS associations to biology in BE/EAC, and supports the utility of functional potential scores to guide variant prioritization. Our findings reveal a functional variant and candidate risk enhancer at chr19p13.11, and implicate CRTC1 and COMP as putative gene targets, suggesting that altered expression of these genes may underlie the BE/EAC risk association.
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Affiliation(s)
- Jianhong Chen
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263 USA
| | - Mourad Wagdy Ali
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22903 USA
| | - Li Yan
- Department of Biostatistics and Bioinformatics, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263 USA
| | - Shruti G Dighe
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263 USA
| | - James Y Dai
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109 USA
| | - Thomas L Vaughan
- Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109 USA.,Department of Epidemiology, University of Washington, School of Public Health, Seattle, Washington, 98195 USA
| | - Graham Casey
- Center for Public Health Genomics, Department of Public Health Sciences, University of Virginia, Charlottesville, VA 22903 USA
| | - Matthew F Buas
- Department of Cancer Prevention and Control, Roswell Park Comprehensive Cancer Center, Buffalo, NY, 14263 USA
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Yano Y, Etemadi A, Abnet CC. Microbiome and Cancers of the Esophagus: A Review. Microorganisms 2021; 9:1764. [PMID: 34442842 PMCID: PMC8398938 DOI: 10.3390/microorganisms9081764] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2021] [Revised: 08/11/2021] [Accepted: 08/14/2021] [Indexed: 01/04/2023] Open
Abstract
Esophageal cancer (EC) is an aggressive malignant disease ranking amongst the leading causes of cancer deaths in the world. The two main histologic subtypes, esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC), have distinct geographic and temporal patterns and risk factor profiles. Despite decades of research, the factors underlying these geo-temporal patterns are still not fully understood. The human microbiome has recently been implicated in various health conditions and disease, and it is possible that the microbiome may play an important role in the etiology of EC. Although studies of the microbiome and EC are still in their early stages, we review our current understanding of the potential links between ESCC, EAC, and bacterial communities in the oral cavity and esophagus. We also provide a summary of the epidemiology of EC and highlight some key challenges and future directions.
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Affiliation(s)
- Yukiko Yano
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA; (A.E.); (C.C.A.)
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