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Ren J, Tang C, Wang J, Wang Y, Yang D, Sheng J, Zhu S, Liu Y, Li X, Liu W. Association of overweight/obesity and digestive system cancers: A meta-analysis and trial sequential analysis of prospective cohort studies. PLoS One 2025; 20:e0318256. [PMID: 40168281 PMCID: PMC11960891 DOI: 10.1371/journal.pone.0318256] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Accepted: 01/14/2025] [Indexed: 04/03/2025] Open
Abstract
BACKGROUND Previous researches have reported correlations between overweight/obesity and common digestive system cancers (DSCs), including gastric, liver, esophageal, colorectal, and pancreatic cancers. However, the inconsistency in defining overweight/obesity and the risk of recall bias from case-control and retrospective cohort studies may influence existing results. Therefore, we aimed to validate the relationship between overweight/obesity and common DSCs by combining prospective cohort studies based on the World Health Organization (WHO) criteria for defining overweight/obesity. METHODS A comprehensive literature search was conducted across PubMed, Embase, Web of Science, and Cochrane databases, covering all publications up to February 7, 2024. The inclusion criteria focused on prospective cohort studies that examined the link between overweight/obesity and risks of DSCs. R software 4.1.3 and STATA 12 were utilised to calculate the relative risk (RR), with 95% confidence interval (CI) and prediction interval (PI). TSA v0.9.5.10 Beta software was used for trial sequential analysis (TSA). RESULTS The meta-analysis encompassed 39 articles. The overall analysis showed that compared with normal weight, overweight/obesity increased the risks of liver cancer (overweight: RR [95% CI] = 1.237 [1.112-1.377]; 95% PI: 0.888-1.725; obesity: RR [95% CI] = 1.642 [1.466-1.839]; 95% PI: 1.143-2.358) and colorectal cancer (overweight: RR [95% CI] = 1.124 [1.056-1.197]; 95% PI: 0.931-1.357; obesity: RR [95% CI] = 1.366 [1.242-1.503]; 95% PI: 0.959-1.945) in the total population. Subgroup analysis revealed that overweight (RR [95% CI] = 1.237 [1.165-1.314]; 95% PI: 1.154-1.327) and obesity (RR [95% CI] = 1.306 [1.152-1.480]; 95% PI: 1.108-1.539) were associated with an increased risk of pancreatic cancer only in women, and overweight also increased the gastric cancer risk of women (RR [95% CI] = 1.041 [1.013-1.070], 95% PI: 0.806-1.230). No significant association of overweight/obesity and esophageal cancer was observed in both male and female. CONCLUSION Our study suggested that overweight/obesity elevated the risks of liver and colorectal cancer in both men and women. No significant association was found between overweight/obesity and the risk of developing esophageal cancer. Clinicians are advised to consider weight control as an effective measure for preventing pancreatic, liver, and colorectal cancers.
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Affiliation(s)
- Ji Ren
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Chunyan Tang
- Department of Nursing, Dezhou Municipal Hospital (Dezhou University Affiliated Hospital), Dezhou, China
| | - Jinghe Wang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Yanan Wang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Dongying Yang
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Jianming Sheng
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Shili Zhu
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Yunli Liu
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Xiaoqi Li
- Department of Medicine and Health, Dezhou University, Dezhou, China
| | - Wei Liu
- Department of Medicine and Health, Dezhou University, Dezhou, China
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Lei S, Huang G, Li X, Xi P, Yao Z, Lin X. Global Burden, Trends, and Inequalities of Gallbladder and Biliary Tract Cancer, 1990-2021: A Decomposition and Age-Period-Cohort Analysis. Liver Int 2025; 45:e16199. [PMID: 39742398 DOI: 10.1111/liv.16199] [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] [Received: 09/13/2024] [Revised: 11/12/2024] [Accepted: 11/25/2024] [Indexed: 01/03/2025]
Abstract
BACKGROUND Gallbladder and biliary tract cancer (GBTC) increasingly aggravates the global malignancy burden. This study aimed to evaluate the updated condition of GBTC temporal burden trends and inequalities from 1990 to 2021. METHODS Data on GBTC were extracted from the Global Burden of Disease (GBD) 2021 study. Incidence, deaths, and disability-adjusted life years (DALYs) and their age-standardised rates (ASR) were quantified from 1990 to 2021, stratified by sex, age and sociodemographic index (SDI). The age-period-cohort (APC) model was used to elucidate the effects of age, period, and cohort. Decomposition analysis and cross-country inequality evaluation were performed to assess the contributing factors and disease imbalance, respectively. Bayesian APC analysis was used to estimate the future burden. RESULTS In 2021, the global incident cases of GBTC were 216 768, with 171 961 deaths and 3 732 121 DALYs lost. From 1990 to 2021, the ASR of incidence, mortality, and DALYs decreased slightly. Males showed a slight increase in ASR of incidence, while females experienced a significant decrease. High-income regions, particularly in Asia Pacific and Latin America, exhibited a higher burden, while Western Sub-Saharan Africa had the lowest. Low and low-middle SDI regions showed a gradual rise in all metrics despite lower absolute numbers. The APC analysis indicated that the global incidence of GBTC tended to rise with age, but gender differences existed. Besides, a deteriorating cohort effect was detected amongst individuals born between 1907 and 1917. Decomposition analysis revealed that population growth was the primary driver of the increased GBTC burden globally. Significant disparities in GBTC burden by SDI were observed, with a notable decline in inequality over time. Projections indicated a slow decline in the global ASR through 2040, with a more pronounced decrease in females. CONCLUSIONS There are significant regional and gender differences in the global burden of GBTC. Population growth remains a major contributor to the burden. Despite the overall decline, the increasing incidence in low and lower-middle SDI regions and the persistent male burden highlight the need for targeted interventions. Future efforts should focus on addressing socio-economic inequalities and reducing risk factors, particularly in vulnerable populations.
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Affiliation(s)
- Sen Lei
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
| | - Guizhong Huang
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
| | - Xiaohui Li
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Sun Yat-Sen University, Sun Yat-Sen University, Guangzhou, China
| | - Pu Xi
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
| | - Zehui Yao
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
| | - Xiaojun Lin
- Department of Pancreatobiliary Surgery, State Key Laboratory of Oncology in South China, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, P. R. China
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Zhao SS, Bai RR, Zhang BH, Sun XR, Huang N, Chen Y, Sun ZJ, Sun LM, Zhang Y, Cui ZQ. Investigating the diagnostic and prognostic significance of genes related to fatty acid metabolism in hepatocellular carcinoma. BMC Gastroenterol 2024; 24:409. [PMID: 39548390 PMCID: PMC11566841 DOI: 10.1186/s12876-024-03495-2] [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] [Received: 06/23/2024] [Accepted: 11/05/2024] [Indexed: 11/18/2024] Open
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most prevalent and lethal cancers worldwide, with death rates increasing by approximately 2-3% per year. The high mortality and poor prognosis of HCC are primarily due to inaccurate early diagnosis and lack of monitoring when liver transplantation is not feasible. Fatty acid (FA) metabolism is a critical metabolic pathway that provides energy and signaling factors in cancer, particularly in HCC, and promotes malignancy. Therefore, it is essential to explore specific FA metabolism-related diagnostic and prognostic signatures that can enable the effective early diagnosis and monitoring of HCC. METHODS In this study, we used genes associated with FA metabolism pathway and weighted gene co-expression network analysis (WGCNA) to establish a gene co-expression network and identify hub genes related to HCC (disease WGCNA) and FA clusters (cluster WGCNA). A diagnostic model was constructed using data downloaded from the Gene Expression Omnibus database (GSE25097), and a prognostic model was established using The Cancer Genome Atlas cohort, in which Univariate Cox regression analysis, multivariate Cox risk model, and LASSO Cox regression analysis were applied. The immune infiltration of HCC cells was evaluated using CIBERSORT. The function of the key SLC22A1 gene was experimentally verified in vitro and in vivo. RESULTS Twelve overlapping genes (CPEB3, ASPDH, DEPDC7, ETFDH, UGT2B7, GYS2, F11, ANXA10, CYP2C8, GLYATL1, C6, and SLC22A1) from disease and cluster WGCNA were identified as key genes and used in the construction of the diagnostic and prognostic models. The RF model had the highest area under the ROC curve (AUC) of 0.994 was identified as the most effective for distinguishing patients with HCC with different features. The top five important genes (C6, UGT2B7, SLC22A1, F11, and CYP2C8) from the RF model were selected as diagnostic genes for further analysis (ROC curves: AUC value = 0.986, 95% confidence interval [95% CI] = 0.967-0.999). Moreover, a risk score formula consisting of four genes (GYS2, F11, ANXA10 and SLC22A1) was established and its independent prognostic ability was further demonstrated (univariate Cox regression analysis: hazard ratio [HR] = 3.664%, 95% CI = 2.033-6.605, P < 0.001; multivariate Cox regression analysis: HR = 2.801%, 95% CI = 1.553-5.049, P < 0.001). Additionally, in vitro and in vivo experiments demonstrated that SLC22A1 inhibits HCC tumor development, suggesting it may be a potential therapeutic target for HCC. CONCLUSIONS These findings indicate a considerable value of specific FA metabolism-related genes in the diagnostic and prognostic evaluation of HCC, which provide novel insights into the disease's management, as well as has potential implications for personalized treatment strategies. However, further investigation of the effects of these model genes on HCC is required.
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Affiliation(s)
- Sha-Sha Zhao
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | - Rong-Rong Bai
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
- Suzhou Medical College of Soochow University, Suzhou, PR China
| | - Bao-Hua Zhang
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | | | - Nan Huang
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | - Yan Chen
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | - Zi-Jiu Sun
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China
| | - Li-Mei Sun
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
| | - Yue Zhang
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
- Department of Clinical Laboratory, Clinical Medicine Scientific and Technical Innovation Park, Shanghai Tenth People's Hospital, Shanghai, 200435, China.
| | - Zhong-Qi Cui
- Department of Clinical Laboratory, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
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Szablewski L. Insulin Resistance: The Increased Risk of Cancers. Curr Oncol 2024; 31:998-1027. [PMID: 38392069 PMCID: PMC10888119 DOI: 10.3390/curroncol31020075] [Citation(s) in RCA: 29] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2023] [Revised: 01/15/2024] [Accepted: 02/10/2024] [Indexed: 02/24/2024] Open
Abstract
Insulin resistance, also known as impaired insulin sensitivity, is the result of a decreased reaction of insulin signaling to blood glucose levels. This state is observed when muscle cells, adipose tissue, and liver cells, improperly respond to a particular concentration of insulin. Insulin resistance and related increased plasma insulin levels (hyperinsulinemia) may cause metabolic impairments, which are pathological states observed in obesity and type 2 diabetes mellitus. Observations of cancer patients confirm that hyperinsulinemia is a major factor influencing obesity, type 2 diabetes, and cancer. Obesity and diabetes have been reported as risks of the initiation, progression, and metastasis of several cancers. However, both of the aforementioned pathologies may independently and additionally increase the cancer risk. The state of metabolic disorders observed in cancer patients is associated with poor outcomes of cancer treatment. For example, patients suffering from metabolic disorders have higher cancer recurrence rates and their overall survival is reduced. In these associations between insulin resistance and cancer risk, an overview of the various pathogenic mechanisms that play a role in the development of cancer is discussed.
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Affiliation(s)
- Leszek Szablewski
- Chair and Department of General Biology and Parasitology, Medical University of Warsaw, Chałubińskiego 5 Str., 02-004 Warsaw, Poland
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Mai Y, Meng L, Deng G, Qin Y. The Role of Type 2 Diabetes Mellitus-Related Risk Factors and Drugs in Hepatocellular Carcinoma. J Hepatocell Carcinoma 2024; 11:159-171. [PMID: 38268569 PMCID: PMC10806369 DOI: 10.2147/jhc.s441672] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Accepted: 01/04/2024] [Indexed: 01/26/2024] Open
Abstract
With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients. In addition, reports have indicated the different effects of anti-DM drugs on the progression of HCC. In this review, we summarize the effects of major T2DM-related risk factors (including hyperglycemia, hyperinsulinemia, insulin, chronic inflammation, obesity, nonalcoholic fatty liver disease, gut microbiota and immunomodulation), and anti-DM drugs on the carcinogensis and progression of HCC, as well as their potential molecular mechanisms. In addition, other factors (miRNAs, genes, and lifestyle) related to T2DM-related HCC are discussed. We propose a refined concept by which T2DM-related risk factors and anti-DM drugs contribute to HCC and discuss research directions prompted by such evidence worth pursuing in the coming years. Finally, we put forward novel therapeutic approaches to improve the prognosis of T2DM-related HCC, including exploiting novel diagnostic biomarkers, combination therapy with immunocheckpoint inhibitors, and enhancement of the standardized management of T2DM patients.
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Affiliation(s)
- Yuhua Mai
- Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China
| | - Liheng Meng
- Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
| | - Ganlu Deng
- Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China
- Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
| | - Yingfen Qin
- Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China
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6
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Qin SS, Pan GQ, Meng QB, Liu JB, Tian ZY, Luan SJ. The causal relationship between metabolic factors, drinking, smoking and intrahepatic cholangiocarcinoma: a Mendelian randomization study. Front Oncol 2023; 13:1203685. [PMID: 37427123 PMCID: PMC10325926 DOI: 10.3389/fonc.2023.1203685] [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: 04/11/2023] [Accepted: 06/05/2023] [Indexed: 07/11/2023] Open
Abstract
Background Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer. While multiple risk factors for iCCA have been established, metabolic diseases (obesity, diabetes, NAFLD, dyslipidemia, and hypertension) and other risk factors, including smoking and drinking, are still controversial due to their potential confounders. Here, Mendelian randomization (MR) analysis was performed to identify the causal relationship between them. Method In this study, we obtained GWAS data related to exposures from corresponding large genome-wide association studies. Summary-level statistical data for iCCA were obtained from the UK Biobank (UKB). We performed a univariable MR analysis to identify whether genetic evidence of exposure was significantly associated with iCCA risk. A multivariable MR analysis was conducted to estimate the independent effects of exposures on iCCA. Results Univariable and multivariable MR analysis based on the large GWAS data indicated that there is little evidence to support the genetic role of metabolic factors, smoking, drinking, and NAFLD in iCCA development (P >0.05). In contrast to most current studies, their impact on iCCA development, if any, might be smaller than we thought. The previous positive results might be due to the comorbidities between diseases and potentially unavoidable confounding factors. Conclusion In this MR study, we found no strong evidence to support causal associations between metabolic factors, NAFLD, smoking, drinking, and iCCA risk.
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Affiliation(s)
- Shan-shan Qin
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Guo-qiang Pan
- Department of General Surgery, Qilu Hospital, Shandong University, Jinan, China
| | - Qun-bo Meng
- Department of Orthopaedical Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Jin-bo Liu
- Department of Orthopaedical Surgery, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan, China
| | - Zi-yu Tian
- Department of Radiology, Qilu Hospital, Shandong University, Jinan, China
| | - Shou-jing Luan
- Department of Endocrinology, Weifang People’s Hospital, Weifang, China
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Liu Y, Chou B, Yalamanchili A, Lim SN, Dawson LA, Thomas TO. Local Therapies for Hepatocellular Carcinoma and Role of MRI-Guided Adaptive Radiation Therapy. J Clin Med 2023; 12:jcm12103517. [PMID: 37240623 DOI: 10.3390/jcm12103517] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/19/2023] [Accepted: 05/06/2023] [Indexed: 05/28/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common liver tumor, with a continually rising incidence. The curative treatment for HCC is surgical resection or liver transplantation; however, only a small portion of patients are eligible due to local tumor burden or underlying liver dysfunction. Most HCC patients receive nonsurgical liver-directed therapies (LDTs), including thermal ablation, transarterial chemoembolization (TACE), transarterial radioembolization (TARE), and external beam radiation therapy (EBRT). Stereotactic ablative body radiation (SABR) is a specific type of EBRT that can precisely deliver a high dose of radiation to ablate tumor cells using a small number of treatments (or fractions, typically 5 or less). With onboard MRI imaging, MRI-guided SABR can improve therapeutic dose while minimizing normal tissue exposure. In the current review, we discuss different LDTs and compare them with EBRT, specifically SABR. The emerging MRI-guided adaptive radiation therapy has been reviewed, highlighting its advantages and potential role in HCC management.
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Affiliation(s)
- Yirong Liu
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Brian Chou
- Department of Radiation Oncology, Loyola University Medical Center, Maywood, IL 60153, USA
| | - Amulya Yalamanchili
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Sara N Lim
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
| | - Laura A Dawson
- Department of Radiation Oncology, Princess Margaret Cancer Centre, University of Toronto, Toronto, ON M5S 1A1, Canada
| | - Tarita O Thomas
- Department of Radiation Oncology, Northwestern Medicine, Chicago, IL 60611, USA
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Yan LJ, Yang LS, Yan YC, Tan SY, Ding ZN, Liu H, Wang DX, Dong ZR, Li T. Anthropometric indicators of adiposity and risk of primary liver cancer: A systematic review and dose-response meta-analysis. Eur J Cancer 2023; 185:150-163. [PMID: 36996625 DOI: 10.1016/j.ejca.2023.03.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2022] [Revised: 01/29/2023] [Accepted: 03/01/2023] [Indexed: 03/09/2023]
Abstract
BACKGROUND AND AIMS Adiposity is associated with an increased risk of primary liver cancer (PLC). As the most commonly used indicator of adiposity, the body mass index (BMI) has been questioned for its limitations in reflecting visceral fat. This study aimed to investigate the role of different anthropometric indicators in identifying the risk of PLC by accounting for potential non-linear associations. METHODS Systematic searches were conducted in the PubMed, Embase, Cochrane Library, Sinomed, Web of Science, and CNKI databases. Hazard ratios (HRs) and the corresponding 95% confidence intervals (CIs) were used to assess the pooled risk. The dose-response relationship was assessed using a restricted cubic spline model. RESULTS Sixty-nine studies involving more than 30 million participants were included in the final analysis. Regardless of the indicator used, adiposity was strongly associated with an increased risk of PLC. When comparing the HRs per 1-standard deviation increment across indicators of adiposity, the association was strongest for waist-to-height ratio (WHtR) (HR = 1.39), followed by waist-to-hip ratio (WHR) (HR = 1.22), BMI (HR = 1.13), waist circumference (WC) (HR = 1.12), and hip circumference (HC) (HR = 1.12). A strong non-linear association was observed between each anthropometric parameter and the risk of PLC, regardless of whether the original or decentralised value was used. The positive association between WC and PLC risk remained substantial after adjusting for BMI. The incidence of PLC was higher with central adiposity (52.89 per 100,000 person-years, 95% CI = 50.33-55.44) than general adiposity (39.01 per 100,000 person-years, 95% CI = 37.26-40.75). CONCLUSION Central adiposity seems to contribute more to the development of PLC than general adiposity. A larger WC, independent of BMI, was strongly associated with the risk of PLC and might be a more promising predictive indicator than BMI.
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Affiliation(s)
- Lun-Jie Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Long-Shan Yang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Yu-Chuan Yan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Si-Yu Tan
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zi-Niu Ding
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Hui Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Dong-Xu Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China
| | - Zhao-Ru Dong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China.
| | - Tao Li
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan 250012, PR China; Department of Hepatobiliary Surgery, The Second Hospital of Shandong University, Jinan 250012, PR China.
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Zhang YH, Chen XL, Wang YR, Hou YW, Zhang YD, Wang KJ. Prevention of malignant digestive system tumors should focus on the control of chronic inflammation. World J Gastrointest Oncol 2023; 15:389-404. [PMID: 37009320 PMCID: PMC10052658 DOI: 10.4251/wjgo.v15.i3.389] [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: 10/28/2022] [Revised: 01/17/2023] [Accepted: 02/07/2023] [Indexed: 03/14/2023] Open
Abstract
Chronic inflammation, through a variety of mechanisms, plays a key role in the occurrence and development of digestive system malignant tumors (DSMTs). In this study, we feature and provide a comprehensive understanding of DSMT prevention strategies based on preventing or controlling chronic inflammation. The development and evaluation of cancer prevention strategies is a longstanding process. Cancer prevention, especially in the early stage of life, should be emphasized throughout the whole life course. Issues such as the time interval for colon cancer screening, the development of direct-acting antiviral drugs for liver cancer, and the Helicobacter pylori vaccine all need to be explored in long-term, large-scale experiments in the future.
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Affiliation(s)
- Yue-Hua Zhang
- College of Public Health, Zhengzhou University, Zhengzhou 450001, Henan Province, China
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Xiao-Lin Chen
- Department of Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
| | - Yi-Ran Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yu-Wei Hou
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Yao-Dong Zhang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
| | - Kai-Juan Wang
- Henan International Joint Laboratory of Prevention and Treatment of Pediatric Diseases, Henan Children's Hospital Zhengzhou Children’s Hospital, Children's Hospital Affiliated to Zhengzhou University, Zhengzhou 450018, Henan Province, China
- Henan Children’s Hospital Zhengzhou Children’s Hospital, Children’s Hospital Affiliated to Zhengzhou University, Key Laboratory of Tumor Epidemiology of Henan Province, State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou 450001, Henan Province, China
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Alharbi TA, Ryan J, Freak-Poli R, Gasevic D, McNeil J, Woods RL, Britt C, Nelson MR, Owen AJ. Self-Reported Early and Later Life Weight and the Risk of All-Cause Mortality in Older Adults. J Nutr Health Aging 2023; 27:301-308. [PMID: 37170438 PMCID: PMC10353754 DOI: 10.1007/s12603-023-1907-1] [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: 07/12/2022] [Accepted: 01/25/2023] [Indexed: 05/13/2023]
Abstract
OBJECTIVES The extent to which body weight in early adulthood is associated with late-life mortality risk is unclear. This study aimed to determine the association between body mass index (BMI) in early adulthood (at 18 years of age) and older age (70 years and over), and the risk of mortality in later life. DESIGN Secondary analysis of the ASPREE Longitudinal Study of Older Persons (ALSOP). SETTING, PARTICIPANTS Data were from 14,853 relatively healthy community-dwelling Australians aged ≥ 70 years when enrolled in the study. MEASUREMENTS Self-reported weight at age ≥ 70 years and recalled weight at age 18 years were collected at ALSOP study baseline. Height was measured with a stadiometer and was used for calculation of BMI at both timepoints. BMI at each timepoint was defined as: underweight, normal weight, overweight and obese. Individuals were categorised into one of five 'lifetime' BMI groups: normal weight (BMI between 18.5 and 24.9 at both times), overweight (25.0-29.9 at either or both times), obesity to non-obese (≥30.0 at age 18 and <30.0 ≥ 70 years), non-obese to obesity (<30.0 at age 18 and ≥30.0 at age ≥ 70 years), and early and later life obesity (≥30.0 at both times). RESULTS During a median 4.7 years follow-up, 715 deaths occurred. Obesity at 18 years, but not in older age (p=0.44), was significantly associated with the risk of mortality in later life, even after accounting for current health status (HR: 2.35, 95% CI: 1.53-3.58, p<0.001). Compared with participants with normal BMI at both time points, being obese at both time points was associated with increased mortality risk (HR=1.99, 95% CI: 1.04-3.81, p=0.03), and the risk was even greater for individuals who were obese at 18 years but were no longer obese in older age (HR=2.92, 95% CI: 1.65-5.16, p<0.001), in fully adjusted models. Participants who were normal weight at 18 years and were obese in later life, did not have an increased mortality risk (p=0.78). CONCLUSIONS Obesity in early adulthood, and obesity in both early and later life, were associated with increased mortality risk in later life. This highlights the importance of preventing obesity in early adulthood and maintaining a normal weight over an adult lifespan.
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Affiliation(s)
- T A Alharbi
- Dr Alice J. Owen, Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, 553 St. Kilda Rd., Level 4, Melbourne VIC 3004, Australia, Tel: +61 3 9903 0416,
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11
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Yang W, Zeng X, Petrick JL, Danford CJ, Florio AA, Lu B, Nan H, Ma J, Wang L, Zeng H, Sudenga SL, Campbell PT, Giovannucci E, McGlynn KA, Zhang X. Body mass index trajectories, weight gain and risks of liver and biliary tract cancers. JNCI Cancer Spectr 2022; 6:pkac056. [PMID: 35960613 PMCID: PMC9406603 DOI: 10.1093/jncics/pkac056] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2022] [Revised: 05/18/2022] [Accepted: 06/06/2022] [Indexed: 11/23/2022] Open
Abstract
BACKGROUND Little is known about the role of early obesity or weight change during adulthood in the development of liver cancer and biliary tract cancer (BTC). METHODS We investigated the associations of body mass index (BMI) and weight trajectories with the risk of liver cancer and BTC in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO). BMI was self-reported at ages 20, 50, and at enrollment. BMI trajectories were determined using latent class growth models. Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS During a median follow-up of 15.9 years among 138,922 participants, 170 liver cancer and 143 BTC cases were identified. Compared with those whose BMI does not exceed 25 kg/m2, participants with BMI exceeding 25 kg/m2 at age 20 had increased risks of liver cancer (HR = 2.03, 95% CI: 1.26-3.28) and BTC (HR = 1.99, 95% CI: 1.16-3.39). Compared to participants maintaining normal BMI until enrollment, trajectory of normal weight at age 20 to obesity at enrollment was associated with increased risk for liver cancer (HR = 2.50, 95% CI: 1.55-4.04) and BTC (HR = 1.83, 95% CI: 1.03-3.22). Compared to adults with stable weight (+/-5kg) between age 20 to 50 years, weight gain ≥20 kg between ages 20 to 50 years had higher HRs of 2.24 (95%CI: 1.40-3.58) for liver cancer and 1.86 (95% CI: 1.12-3.09) for BTC. CONCLUSIONS Being overweight/obese at age 20, and BMI trajectories that result in being overweight and/or obese, may increase risk for both liver cancer and BTC.
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Affiliation(s)
- Wanshui Yang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China
| | - Xufen Zeng
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China
| | | | - Christopher J Danford
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Andrea A Florio
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Bing Lu
- Division of Rheumatology, Inflammation and Immunity, Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA
| | - Hongmei Nan
- Department of Epidemiology, Richard M Fairbanks School of Public Health, Indiana University, and Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN, USA
| | - Jiantao Ma
- Framingham Heart Study, Framingham, MA, USA
- Division of Nutrition Data Science, Tufts University Friedman School of Nutrition Science and Policy, Boston, MA, USA
| | - Liang Wang
- Department of Public Health, Robbins College of Health and Human Sciences, Baylor University, TX, USA
| | - Hongmei Zeng
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Staci L Sudenga
- Division of Epidemiology, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Peter T Campbell
- Department of Epidemiology and Population Science, Albert Einstein College of Medicine, Bronx, NY, USA
| | - Edward Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
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12
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Befort CA, Weinman SA. Obesity and Risk of Liver and Biliary Tract Cancer: Does Timing and Trajectory Matter? JNCI Cancer Spectr 2022; 6:pkac057. [PMID: 35944215 PMCID: PMC9406598 DOI: 10.1093/jncics/pkac057] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 07/22/2022] [Accepted: 07/24/2022] [Indexed: 11/16/2022] Open
Affiliation(s)
- Christie A Befort
- Department of Population Health, University of Kansas Medical Center, Kansas City, KS, USA
| | - Steven A Weinman
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, University of Kansas Medical Center, Kansas City, KS, USA
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13
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The timing of adiposity and changes in the life course on the risk of cancer. Cancer Metastasis Rev 2022; 41:471-489. [PMID: 35908000 DOI: 10.1007/s10555-022-10054-2] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2022] [Accepted: 07/23/2022] [Indexed: 11/02/2022]
Abstract
Excess body weight has been established as a risk factor for at least twelve cancer sites, though questions remain as to the timing of associations for adiposity and cancer risk throughout the life course. We conducted a narrative review summarizing existing evidence to provide insights into the complex timing relationship between adiposity and risk of seven common obesity-related cancers. We considered five types of studies, including traditional epidemiologic studies examining adiposity at different time points, studies examining weight gain in specific life phases, studies examining weight loss over a period including from bariatric surgery, life course trajectory analysis, and Mendelian randomization studies. The results showed that lifetime excess body weight is associated with increased risk of cancers of endometrium, colorectum, liver, kidney, and pancreas. Early life obesity is one of the strongest risk factors for pancreatic cancer but less directly important than adult obesity for endometrial and kidney cancer. Interestingly, heavy weight during childhood, adolescence, and early adulthood is protective against pre- and postmenopausal breast cancer and possibly advanced prostate cancer. It is apparent that preventing weight gain later in adulthood would likely reduce risk of many cancers, including postmenopausal breast cancer, endometrial cancer, colorectal cancer (especially in men), liver cancer, kidney cancer, and probably advanced prostate cancer. Furthermore, weight loss even late in life may confer benefits for cancers of breast, endometrium, colorectum, and liver among patients with obesity, as mostly demonstrated by studies of bariatric surgery. Overall, maintaining a healthy weight throughout the life course will help prevent a large number of cancers.
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14
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Osataphan S, Mahankasuwan T, Saengboonmee C. Obesity and cholangiocarcinoma: A review of epidemiological and molecular associations. JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 2021; 28:1047-1059. [PMID: 34053180 DOI: 10.1002/jhbp.1001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/02/2021] [Accepted: 05/19/2021] [Indexed: 11/10/2022]
Abstract
Cholangiocarcinoma (CCA) is a malignancy of bile duct epithelium, and its incidence is increasing globally. Numerous factors are reported associated with an increased risk of CCA and vary among populations across different areas. Obesity is a major, worldwide public health problem that leads to several complications and is associated with increased cancer risk. Although several epidemiological studies have shown that obesity is likely associated with the increased risk of CCA, this association might be limited to Western countries. Multiple hormones, cytokines, and metabolite perturbations in obese states have been shown to enhance tumorigenicity and metastasis potentials. Understanding the biological linkage of obesity to CCA might lead to novel prevention and therapeutic approaches to CCA treatment. This review summarizes the current evidence and highlights the knowledge gaps regarding the relationship between obesity and CCA from epidemiological and molecular perspectives.
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Affiliation(s)
| | | | - Charupong Saengboonmee
- Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
- Cholangiocarcinoma Research Institute, Khon Kaen University, Khon Kaen, Thailand
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15
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Philips CA, Rajesh S, Nair DC, Ahamed R, Abduljaleel JK, Augustine P. Hepatocellular Carcinoma in 2021: An Exhaustive Update. Cureus 2021; 13:e19274. [PMID: 34754704 PMCID: PMC8569837 DOI: 10.7759/cureus.19274] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 11/04/2021] [Indexed: 02/06/2023] Open
Abstract
Primary liver cancer is a challenging global health concern with an estimated more than a million persons to be affected annually by the year 2025. The commonest type is hepatocellular carcinoma (HCC), which has been increasing in incidence the world over, mostly due to chronic viral hepatitis B infection. In the last decade, paradigm changes in the etiology, understanding of molecular biology, and pathogenesis, including the role of gut microbiota; medical and surgical treatments, and outcome trends are notable. The application of omics-based technology has helped us unlock the molecular and immune landscape of HCC, through which novel targets for drug treatment such as immune-checkpoint inhibitors have been identified. Novel tools for the surveillance and diagnosis of HCC include protein-, genomics-, and composite algorithm-based clinical/biomarker panels. Magnetic resonance imaging-based novel techniques have improved HCC diagnosis through ancillary features that enhance classical criteria while positron emission tomography has shown value in prognostication. Identification of the role of gut microbiota in the causation and progression of HCC has opened areas for novel therapeutic research. A select group of patients still benefit from modified surgical and early interventional radiology treatments. Improvements in radiotherapy protocols, identification of parameters of futility among radiological interventions, and the emergence of novel first-line systemic therapies that include a combination of antiangiogenic and immune-checkpoint inhibitors have seen a paradigm change in progression-free and overall survival. The current review is aimed at providing exhaustive updates on the etiology, molecular biology, biomarker diagnosis, imaging, and recommended treatment options in patients with HCC.
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Affiliation(s)
- Cyriac A Philips
- Clinical and Translational Hepatology, The Liver Institute, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Sasidharan Rajesh
- Interventional Hepatobiliary Radiology, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Dinu C Nair
- Interventional Hepatobiliary Radiology, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Rizwan Ahamed
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Jinsha K Abduljaleel
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
| | - Philip Augustine
- Gastroenterology and Advanced Gastrointestinal (GI) Endoscopy, Center of Excellence in GI Sciences, Rajagiri Hospital, Aluva, IND
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16
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Simon TG, Kim MN, Luo X, Liu X, Yang W, Ma Y, Chong DQ, Fuchs CS, Stampfer M, Giovannucci EL, Chan AT, Zhang X. Adiposity, Adulthood Weight Change, and Risk of Incident Hepatocellular Carcinoma. Cancer Prev Res (Phila) 2021; 14:945-954. [PMID: 34266856 PMCID: PMC8492521 DOI: 10.1158/1940-6207.capr-20-0549] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 03/11/2021] [Accepted: 07/06/2021] [Indexed: 11/16/2022]
Abstract
Prospective data are limited regarding dynamic adulthood weight changes and hepatocellular carcinoma (HCC) risk. We included 77,238 women (1980-2012) and 48,026 men (1986-2012), who recalled young-adult weight [age 18 years (women); 21 years (men)], and provided biennially updated information regarding weight, body mass index (BMI), and comorbidities. Overall adulthood weight change was defined as the difference in weight (kilograms) between young-adulthood and present. Using Cox proportional hazards models, we calculated multivariable adjusted HRs (aHR) and 95% confidence intervals (CI). Over 3,676,549 person-years, we documented 158 incident HCC cases. Elevated HCC risk was observed with higher BMI in both young-adulthood and later-adulthood [continuous aHRs per each 1 unit = 1.05; 95% CI = 1.02-1.09 (P trend = 0.019), and 1.08; 95% CI = 1.06-1.10 (P trend = 0.004), respectively]. Moreover, overall adulthood weight gain was also significantly associated with increased HCC risk (aHR per each 1-kg increase = 1.03; 95% CI = 1.01-1.08; P trend = 0.010), including after further adjusting for young-adult BMI (P trend = 0.010) and later-adult BMI (P trend = 0.008). Compared with adults with stable weight (±5 kg), the multivariable-aHRs with weight gain of 5-<10 kg, 10-<20 kg, and ≥20 kg were, 1.40 (95% CI = 0.67-2.16), 2.09 (95% CI = 1.11-3.95), and 2.61 (95% CI = 1.42-5.22), respectively. In two prospective, nationwide cohorts, adulthood weight gain was significantly associated with increased HCC risk. PREVENTION RELEVANCE: Our data suggest that maintaining a stable weight during adulthood, specifically by preventing weight gain, could represent an important public health strategy for the prevention of hepatocellular carcinoma.
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Affiliation(s)
- Tracey G Simon
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, Massachusetts
| | - Mi Na Kim
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, Massachusetts
- Division of Gastroenterology, Department of Internal Medicine, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, Korea
| | - Xiao Luo
- School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Xing Liu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Fudan University, Shanghai, P.R. China
| | - Wanshui Yang
- Harvard Medical School, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, Anhui, P.R. China
| | - Yanan Ma
- Harvard Medical School, Boston, Massachusetts
- School of Public Health, China Medical University, Shenyang, Liaoning, P.R. China
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
| | - Dawn Q Chong
- National Cancer Centre Singapore, Singapore
- Duke-NUS Medical School, Singapore
| | | | - Meir Stampfer
- Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Edward L Giovannucci
- Harvard Medical School, Boston, Massachusetts
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Andrew T Chan
- Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts
- Harvard Medical School, Boston, Massachusetts
- Clinical and Translational Epidemiology Unit (CTEU), Massachusetts General Hospital, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
- Broad Institute, Boston, Massachusetts
- Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
| | - Xuehong Zhang
- Harvard Medical School, Boston, Massachusetts.
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts
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17
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Li ZY, Li HL, Ji XW, Shen QM, Wang J, Tan YT, Xiang YB. Dose-Response Association between Adiposity and Liver Cancer Incidence: A Prospective Cohort Study among Non-Smoking and Non-Alcohol-Drinking Chinese Women. Cancer Epidemiol Biomarkers Prev 2021; 30:1200-1207. [PMID: 33849965 DOI: 10.1158/1055-9965.epi-20-1610] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Revised: 01/20/2021] [Accepted: 03/31/2021] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND Based on a population with very low prevalence of smoking and alcohol drinking, we examined the associations between overall obesity and fat distribution in middle age, obesity in early adulthood, and adult weight gain with the risk of liver cancer incidence. METHODS The associations between body mass index (BMI) at study enrollment and at age 20, waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), waist-to-height ratio (WHtR), adult weight gain, and annual average weight gain with the risk of liver cancer were estimated using Cox regression models. Multivariable-adjusted HRs and 95% confidence intervals (CIs) were calculated. RESULTS After a mean follow-up time of 17.5 years, 241 liver cancer cases were identified from 69,296 participants. The HRs for per 5-kg/m2 increment of BMI, per 10-cm increment of WC and HC, and per 0.1-unit increment of WHtR in middle age were 1.29 (95% CI, 1.07-1.57), 1.23 (95% CI, 1.05-1.43), 1.30 (95% CI, 1.10-1.55), and 1.37 (95% CI, 1.07-1.75), respectively. The HRs for per 5-kg increment of absolute adult weight gain and per 0.5-kg/year increment of annual average weight gain were 1.15 (95% CI, 1.06-1.25) and 1.44 (95% CI, 1.08-1.92). CONCLUSIONS Overall and abdominal obesity in middle age and weight gain through adulthood were positively associated with liver cancer risk among non-smoking and non-alcohol-drinking women. IMPACT Based on a cohort of non-smoking and non-alcohol-drinking women, the current study confirmed the association between obesity in middle age and increased liver cancer risk and suggested weight gain through adulthood as a risk factor for liver cancer.
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Affiliation(s)
- Zhuo-Ying Li
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Hong-Lan Li
- State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Xiao-Wei Ji
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Qiu-Ming Shen
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China.,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing Wang
- State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yu-Ting Tan
- State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Yong-Bing Xiang
- School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China. .,State Key Laboratory of Oncogene and Related Genes and Department of Epidemiology, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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18
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McGlynn KA, Petrick JL, El-Serag HB. Epidemiology of Hepatocellular Carcinoma. Hepatology 2021; 73 Suppl 1:4-13. [PMID: 32319693 PMCID: PMC7577946 DOI: 10.1002/hep.31288] [Citation(s) in RCA: 1295] [Impact Index Per Article: 323.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Revised: 03/22/2020] [Accepted: 04/10/2020] [Indexed: 02/06/2023]
Abstract
Liver cancer is a major contributor to the worldwide cancer burden. Incidence rates of this disease have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) accounts for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but their importance will likely decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcohol consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence of obesity and diabetes and controlling mycotoxin growth, are just as urgently required.
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Affiliation(s)
- Katherine A McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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Sohn W, Lee HW, Lee S, Lim JH, Lee MW, Park CH, Yoon SK. Obesity and the risk of primary liver cancer: A systematic review and meta-analysis. Clin Mol Hepatol 2020; 27:157-174. [PMID: 33238333 PMCID: PMC7820201 DOI: 10.3350/cmh.2020.0176] [Citation(s) in RCA: 98] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Accepted: 08/31/2020] [Indexed: 12/14/2022] Open
Abstract
Background/Aims In this systematic review and meta-analysis, we aimed to clarify the effect of obesity on the occurrence of and mortality from primary liver cancer. Methods This study was conducted using a systematic literature search of MEDLINE, EMBASE, and the Cochrane Library until November 2018 using the primary keywords “obesity,” “overweight,” “body mass index (BMI),” “body weight,” “liver,” “cancer,” “hepatocellular carcinoma,” “liver cancer,” “risk,” and “mortality.” Studies assessing the relationship between BMI and occurrence of or mortality from primary liver cancer in prospective cohorts and those reporting hazard ratios (HRs) or data that allow HR estimation were included. Results A total of 28 prospective cohort studies with 8,135,906 subjects were included in the final analysis. These included 22 studies with 6,059,561 subjects for cancer occurrence and seven studies with 2,077,425 subjects for cancer-related mortality. In the meta-analysis, an increase in BMI was associated with the occurrence of primary liver cancer (HR, 1.69; 95% confidence interval, 1.50–1.90, I2=56%). A BMI-dependent increase in the risk of occurrence of primary liver cancer was reported. HRs were 1.36 (95% CI, 1.02–1.81), 1.77 (95% CI, 1.56–2.01), and 3.08 (95% CI, 1.21–7.86) for BMI >25 kg/m2, >30 kg/m2, and >35 kg/m2, respectively. Furthermore, increased BMI resulted in enhanced liver cancer-related mortality (HR, 1.61; 95% CI, 1.14–2.27, I2=80%). Conclusions High BMI increases liver cancer mortality and occurrence of primary liver cancer. Obesity is an independent risk factor for the occurrence of and mortality from primary liver cancer.
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Affiliation(s)
- Won Sohn
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Hyun Woong Lee
- Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Sangheun Lee
- Department of Internal Medicine, International St. Mary's Hospital, Catholic Kwandong University College of Medicine, Incheon, Korea
| | - Jin Hong Lim
- Department of General Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea
| | - Min Woo Lee
- Department of Radiology and Center for Imaging Science, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Chan Hyuk Park
- Department of Internal Medicine, Hanyang University Guri Hospital, Hanyang University College of Medicine, Guri, Korea
| | - Seung Kew Yoon
- Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University College of Medicine, Seoul, Korea
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Dou JP, Han ZY, Liu F, Cheng Z, Yu X, Yu J, Liang P. Beneficial body mass index to enhance survival outcomes in patients with early-stage hepatocellular carcinoma following microwave ablation treatment. Int J Hyperthermia 2020; 37:110-118. [PMID: 31969030 DOI: 10.1080/02656736.2020.1712482] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023] Open
Abstract
Purpose: To identify the beneficial body mass index (BMI) for patients with hepatocellular carcinoma (HCC) to achieve longer survival time following curative microwave ablation (MWA).Methods: This retrospective study evaluated 474 patients with solitary primary HCC who underwent MWA. BMI at initial admission and other characteristics were collected. The associations of the BMI with the overall survival (OS) and disease-free survival (DFS) were analyzed by Cox proportional hazards regression analysis in multiple models. A two-piecewise linear regression model was applied to examine the threshold effect of the BMI on OS and DFS by maximized log likelihood method. The threshold level was determined by using trial and error.Results: Patients with a normal BMI range achieved improved survival outcomes but similar DFS in multiple models. In the model with adjustments of the age, size, and Charlson score, patients with BMI ≤ 22.9 and ≤24.9 kg/m2 exhibited a lower death rate than patients with BMI ≤18.5 kg/m2 (p < 0.05). U-shaped relationships between the BMI and OS were illustrated when the BMI was set as a continuous variable. The death prevalence decreased with an increasing BMI up to the first turning point of 21.5 and increased with an increasing BMI up to the second turning point of 23.1 (p = 0.00). The threshold effect analysis indicated that no turning point was selected in the DFS results (p = 0.10).Conclusions: The beneficial BMI level for HCC patients following MWA, with a more likely favorable survival outcome, is 21.5 to 23.1 kg/m2.
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Affiliation(s)
- Jian-Ping Dou
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Zhi-Yu Han
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Fangyi Liu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Zhigang Cheng
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Xiaoling Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Jie Yu
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
| | - Ping Liang
- Department of Interventional Ultrasound, Chinese PLA General Hospital, Beijing, China
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Abstract
Obesity prevalence is rapidly increasing worldwide. It is associated with huge economic and health costs due to its clinical consequences, which includes increased incidence of type 2 diabetes, cardiovascular diseases, and development of different malignancies. In particular, obesity is an independent risk factor for the development of hepatocellular carcinoma (HCC). Indeed, obesity is highly prevalent in patients with non-alcoholic fatty liver disease (NAFLD) that is becoming one of the most frequent causes of liver disease worldwide. NAFLD-related HCC is the most rapidly growing indication for liver transplantation in many countries. The higher mortality rates found in obese HCC patients might be related not only to a worse outcome after HCC treatments, but also to a delayed diagnosis related to a low frequency and a poorer quality of abdominal ultrasonography surveillance that is the test universally used for HCC screening. Given its diffusion, obesity is frequently present in patients with chronic liver diseases related to different etiologies, and in these cases it may increase the HCC risk, acting as an additional co-factor. Indeed, growing evidence demonstrates that a healthy diet and regular physical activity may have an impact in reducing the overall HCC risk. Finally, an impact of obesity in the development of intrahepatic cholangiocarcinoma has been postulated, but more extensive studies are needed to definitively confirm this association.
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Affiliation(s)
- Carlo Saitta
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Italy.
| | - Teresa Pollicino
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Italy; Division of Clinical and Molecular Hepatology, Department of Human Pathology, University of Messina, Italy
| | - Giovanni Raimondo
- Division of Clinical and Molecular Hepatology, Department of Internal Medicine, University Hospital of Messina, Italy; Division of Clinical and Molecular Hepatology, Department of Clinical and Experimental Medicine, University of Messina, Italy
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De Rubeis V, Andreacchi AT, Sharpe I, Griffith LE, Keown‐Stoneman CDG, Anderson LN. Group‐based trajectory modeling of body mass index and body size over the life course: A scoping review. Obes Sci Pract 2020. [PMCID: PMC7909593 DOI: 10.1002/osp4.456] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
Background Group‐based trajectory modeling has been applied to identify distinct trajectories of growth across the life course. Objectives of this study were to describe the methodological approaches for group‐based modeling of growth across the life course and to summarize outcomes across studies. Methods A scoping review with a systematic search of Medline, EMBASE, CINAL, and Web of Science was conducted. Studies that used a group‐based procedure to identify trajectories on any statistical software were included. Data were extracted on trajectory methodology, measures of growth, and association with outcomes. Results A total of 59 studies were included, and most were published from 2013 to 2020. Body mass index was the most common measure of growth (n = 43). The median number of identified trajectories was 4 (range: 2–9). PROC TRAJ in SAS was used by 33 studies, other procedures used include TRAJ in STATA, lcmm in R, and Mplus. Most studies evaluated associations between growth trajectories and chronic disease outcomes (n = 22). Conclusions Group‐based trajectory modeling of growth in adults is emerging in epidemiologic research, with four distinct trajectories observed somewhat consistently from all studies. Understanding life course growth trajectories may provide further insight for population health interventions.
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Affiliation(s)
- Vanessa De Rubeis
- Department of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario Canada
| | - Alessandra T. Andreacchi
- Department of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario Canada
| | - Isobel Sharpe
- Department of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario Canada
| | - Lauren E. Griffith
- Department of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario Canada
| | - Charles D. G. Keown‐Stoneman
- Applied Health Research Centre Li Ka Shing Knowledge Institute St. Michael's Hospital University of Toronto Toronto Ontario Canada
- Division of Biostatistics Dalla Lana School of Public Health University of Toronto Toronto Ontario Canada
| | - Laura N. Anderson
- Department of Health Research Methods, Evidence, and Impact McMaster University Hamilton Ontario Canada
- Child Health Evaluative Sciences The Hospital for Sick Children Research Institute Toronto Ontario Canada
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23
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Abstract
Primary liver cancer is the third leading cause of cancer-related death worldwide. Most patients are diagnosed at late stages with poor prognosis; thus, identification of modifiable risk factors for primary prevention of liver cancer is urgently needed. The well-established risk factors of liver cancer include chronic infection with hepatitis B virus (HBV) or hepatitis C virus (HCV), heavy alcohol consumption, metabolic diseases such as obesity and diabetes, and aflatoxin exposure. However, a large proportion of cancer cases worldwide cannot be explained by current known risk factors. Dietary factors have been suspected as important, but dietary aetiology of liver cancer remains poorly understood. In this review, we summarised and evaluated the observational studies of diet including single nutrients, food and food groups, as well as dietary patterns with the risk of developing liver cancer. Although there are large knowledge gaps between diet and liver cancer risk, current epidemiological evidence supports an important role of diet in liver cancer development. For example, exposure to aflatoxin, heavy alcohol drinking and possibly dairy product (not including yogurt) intake increase, while intake of coffee, fish and tea, light-to-moderate alcohol drinking and several healthy dietary patterns (e.g. Alternative Healthy Eating Index) may decrease liver cancer risk. Future studies with large sample size and accurate diet measurement are warranted and need to consider issues such as the possible aetiological heterogeneity between liver cancer subtypes, the influence of chronic HBV or HCV infection, the high-risk populations (e.g. cirrhosis) and a potential interplay with host gut microbiota or genetic variations.
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24
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Yang Y, Dugué PA, Lynch BM, Hodge AM, Karahalios A, MacInnis RJ, Milne RL, Giles GG, English DR. Trajectories of body mass index in adulthood and all-cause and cause-specific mortality in the Melbourne Collaborative Cohort Study. BMJ Open 2019; 9:e030078. [PMID: 31401610 PMCID: PMC6701564 DOI: 10.1136/bmjopen-2019-030078] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/26/2019] [Revised: 06/07/2019] [Accepted: 07/08/2019] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVE Limited research has assessed the association between patterns of body mass index (BMI) change across adulthood and mortality. We aimed to identify groups of individuals who followed specific group-based BMI trajectories across adulthood, using weight collected on three occasions and recalled data from early adulthood, and to examine associations with all-cause and cause-specific mortality. DESIGN Prospective cohort study. SETTING Melbourne, Australia. PARTICIPANTS Adults (n=29 881) enrolled in the Melbourne Collaborative Cohort Study, who were aged from 40 to 70 years between 1990 and 1994, and had BMI data for at least three time points. OUTCOME Deaths from any cause before 31 March 2017 and deaths from obesity-related cancers, cardiovascular diseases (CVDs) and other causes before 31 December 2013. RESULTS We identified six group-based BMI trajectories: lower-normal stable (TR1), higher-normal stable (TR2), normal to overweight (TR3), chronic borderline obesity (TR4), normal to class I obesity (TR5) and overweight to class II obesity (TR6). Generally, compared with maintaining lower-normal BMI throughout adulthood, the lowest mortality was experienced by participants who maintained higher-normal BMI (HR 0.90; 95% CI 0.84 to 0.97); obesity during midlife was associated with higher all-cause mortality even when BMI was normal in early adulthood (HR 1.09; 95% CI 0.98 to 1.21) and prolonged borderline obesity from early adulthood was also associated with elevated mortality (HR 1.16; 95% CI 1.01 to 1.33). These associations were stronger for never-smokers and for death due to obesity-related cancers. Being overweight in early adulthood and becoming class II obese was associated with higher CVD mortality relative to maintaining lower-normal BMI (HR 2.27; 95% CI 1.34 to 3.87). CONCLUSION Our findings highlight the importance of weight management throughout adulthood to reduce mortality.
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Affiliation(s)
- Yi Yang
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Pierre-Antoine Dugué
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Brigid M Lynch
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
- Physical Activity Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC, Australia
| | - Allison M Hodge
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Amalia Karahalios
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Robert J MacInnis
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Roger L Milne
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Graham G Giles
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
| | - Dallas R English
- Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia
- Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, Univerisity of Melbourne, Melbourne, VIC, Australia
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Wei X, You X, Zhang J, Zhou C. c[RGDyk]-coated liposomes loaded with adriamycin and miR-21 mimics inhibit the growth of hepatoma cell line SMCC-7721 via up-regulating Bax and p53. Transl Cancer Res 2019; 8:1311-1318. [PMID: 35116873 PMCID: PMC8798595 DOI: 10.21037/tcr.2019.07.29] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Accepted: 06/24/2019] [Indexed: 11/06/2022]
Abstract
BACKGROUND This study was conducted to investigate the effects of c[RGDyk]-coated liposomes loaded with Adriamycin (nanodrug) and miR-21 mimics on hepatoma cell line SMCC-7721. METHODS SMCC-7721 cells were divided into five groups: control (receiving no treatment), nanodrug, miR-21 mimics + nanodrug and miR-21 mimics and empty vector. The concentration and duration of treatments were determined using the MTT assay. Cell apoptosis was detected using flow cytometer. The expression of Bax, Bcl-2 and p53 was measured using qPCR and Western blot analysis. RESULTS MTT showed that the nanodrug inhibited cell proliferation. Nanodrug and miR-21 led to cell arrest at S phase and apoptosis. qPCR showed that cells treated with nanodrug and miR-21 increased the expression of Bax and p53. Western blot analysis indicated that Bcl-2 expression was significantly reduced. CONCLUSIONS Our work demonstrates that nanodrug and miR-21 have inhibitory effect on SMCC-7721 cells via up-regulating Bax and p53.
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Affiliation(s)
- Xiaoyong Wei
- Department of General Surgery, The Medical College of Nanchang University, Nanchang 330029, China;,Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, China
| | - Xiaolong You
- Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, China
| | - Jianlong Zhang
- Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, China
| | - Cuncai Zhou
- Department of Hepatobiliary Surgery, Jiangxi Cancer Hospital, Nanchang 330029, China
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26
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Ou X, Zhang GT, Tian PK, Chen JS, Lin ZW, Xie Y, Wang AH, Liu XP, Liu JK. Forkhead box P3 gene silencing inhibits the expression of chemokines and chemokine receptors associated with cell growth, migration, and apoptosis in hepatocellular carcinoma cells. Exp Ther Med 2019; 18:1091-1098. [PMID: 31316604 PMCID: PMC6601415 DOI: 10.3892/etm.2019.7658] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Accepted: 05/02/2019] [Indexed: 01/23/2023] Open
Abstract
The aberrant expression of forkhead box P3 (FOXP3) leads to the formation of malignant tumors. FOXP3 expression levels are also elevated in hepatocellular carcinoma (HCC). The aim of the present study was to investigate the effects of FOXP3 silencing on cell proliferation, migration, apoptosis and chemokine/chemokine receptor expression in the MHCC-97H HCC cell line. Three FOXP3 short hairpin (sh)RNA constructs were designed: Sh-FOXP3-1-pGreenPuro, sh-FOXP3-2-pGreenPuro, and sh-FOXP3-3-pGreenPuro. MHCC-97H cells were transfected with shRNA-FOXP3, and the mRNA and protein expression levels of C-X-C motif chemokine (CXC) ligand 12 (CXCL12), CXCL11, CXC receptor 4 (CXCR4) and CXCR7 were measured. Cell Counting Kit-8, terminal deoxynucleotidyl-transferase-mediated dUTP nick end labeling and Transwell assays were used to evaluate cell proliferation, apoptosis and migration, respectively. Of the three FOXP3 lentivirus carriers constructed, sh-FOXP3-1 significantly reduced FOXP3 expression levels and was chosen for further experiments. sh-FOXP3-1 inhibited cell proliferation, promoted apoptosis and inhibited cell migration compared with the negative control. The mRNA and protein expression levels of CXCL12, CXCL11, CXCR4 and CXCR7 were decreased significantly in response to FOXP3 silencing. FOXP3 silencing may therefore inhibit cell growth, induce apoptosis and inhibit migration in HCC cells, possibly by impairing the chemokine/chemokine receptor axes.
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Affiliation(s)
- Xi Ou
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Guang-Tao Zhang
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Pei-Kai Tian
- Department of Hepatobiliary Surgery, Shenzhen University General Hospital, Shenzhen, Guangdong 518055, P.R. China
| | - Jing-Sen Chen
- Department of Breast Surgery, Shenzhen Maternity and Child Healthcare Hospital, Shenzhen, Guangdong 518028, P.R. China
| | - Ze-Wei Lin
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Yong Xie
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Ai-Hong Wang
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Xiao-Ping Liu
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
| | - Ji-Kui Liu
- Department of Hepatopancreatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
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27
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Abstract
PURPOSE OF REVIEW In prior decades, liver cancer was viewed as a neoplasm that almost exclusively arose among high-risk populations in low- and middle-income countries. Incidence rates in some high-risk populations, however, have been declining, while rates in low-risk populations have been increasing, reflecting changes in underlying etiology. In this review, we highlight the evolving epidemiology of liver cancer, focusing on recent research and advances. RECENT FINDINGS Efforts to reduce or eliminate the risk associated with major risk factors such as hepatitis B virus (HBV), hepatitis C virus (HCV) and aflatoxin B1 (AFB1) have met with some success. As opposed to these favorable trends, the joint epidemics of obesity and diabetes have begun to affect liver cancer rates around the world. SUMMARY While there has been progress in combating the effects of some risk factors, the increasing prevalence of others poses a major threat to attempts to tackle the rising incidence of liver cancer globally.
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Affiliation(s)
- Jessica L. Petrick
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
| | - Katherine A. McGlynn
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD
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28
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Song M. Trajectory analysis in obesity epidemiology: a promising life course approach. CURRENT OPINION IN ENDOCRINE AND METABOLIC RESEARCH 2019; 4:37-41. [PMID: 30906899 PMCID: PMC6426320 DOI: 10.1016/j.coemr.2018.08.002] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Affiliation(s)
- Mingyang Song
- Departments of Epidemiology and Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA
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29
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Murphy N, Jenab M, Gunter MJ. Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions. Nat Rev Gastroenterol Hepatol 2018; 15:659-670. [PMID: 29970888 DOI: 10.1038/s41575-018-0038-1] [Citation(s) in RCA: 125] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Excess adiposity is a risk factor for several cancers of the gastrointestinal system, specifically oesophageal adenocarcinoma and colorectal, small intestine, pancreatic, liver, gallbladder and stomach cancers. With the increasing prevalence of obesity in nearly all regions of the world, this relationship could represent a growing source of cancers of the digestive system. Experimental and molecular epidemiological studies indicate important roles for alterations in insulin signalling, adipose tissue-derived inflammation and sex hormone pathways in mediating the association between adiposity and gastrointestinal cancer. The intestinal microbiome, gut hormones and non alcoholic fatty liver disease (NAFLD) also have possible roles. However, important gaps remain in our knowledge. For instance, our understanding of how adiposity throughout the life course is related to the risk of gastrointestinal cancer development and of how obesity influences gastrointestinal cancer prognosis and survival is limited. Nonetheless, the increasing use of state-of-the-art analytical methods (such as omics technologies, Mendelian randomization and MRI) in large-scale epidemiological studies offers exciting opportunities to advance our understanding of the complex relationship between adiposity and gastrointestinal cancers. Here, we examine the epidemiology of associations between obesity and gastrointestinal cancer, explore potential mechanisms underlying these relationships and highlight important unanswered research questions.
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Affiliation(s)
- Neil Murphy
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Mazda Jenab
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France
| | - Marc J Gunter
- Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
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Hidayat K, Du X, Shi BM. Body fatness at a young age and risks of eight types of cancer: systematic review and meta-analysis of observational studies. Obes Rev 2018; 19:1385-1394. [PMID: 30047231 DOI: 10.1111/obr.12705] [Citation(s) in RCA: 39] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2018] [Revised: 04/13/2018] [Accepted: 04/15/2018] [Indexed: 12/13/2022]
Abstract
The associations between body fatness at a young age (childhood, adolescence and young adulthood; age ≤ 30 years) and diffuse large B-cell lymphoma (DLBCL), oesophageal adenocarcinoma, gastric cardia cancer, hepatocellular carcinoma, multiple myeloma, pancreatic cancer, renal cell cancer and thyroid cancer remain inconclusive. We performed a comprehensive systematic literature review and meta-analysis of observational studies to clarify the associations between body fatness at a young age and the risks of these cancers. PubMed and Web of Science databases were searched for relevant observational studies. Fifty-six articles yielded data on 27,559 cancer cases, including 3,170 DLBCL, 1,491 oesophageal adenocarcinoma, 1,103 gastric cardia cancer, 1,067 hepatocellular carcinoma, 3,090 multiple myeloma, 7,220 pancreatic cancer, 6,212 renal cell cancer and 4,206 thyroid cancer cases. Each 5 kg m-2 increase in body mass index at a young age was positively associated with DLBCL (relative risk [RR] 1.21, 95% confidence interval [CI] 1.09, 1.35), oesophageal adenocarcinoma (RR 1.88, 95% CI 1.37, 2.57), gastric cardia cancer (RR 1.59, 95% CI 1.15, 2.21), hepatocellular carcinoma (RR 1.31, 95% CI 1.13, 1.51), multiple myeloma (RR 1.23, 95% CI 1.15, 1.30), pancreatic cancer (RR 1.17, 95% CI 1.11, 1.24), renal cell cancer (RR 1.22, 95% CI 1.16, 1.28) and thyroid cancer (RR 1.12, 95% CI 1.07, 1.17). In summary, higher body fatness at a young age increases the risks of developing various types of cancer later in life. Prevention of overweight and obesity in children, adolescents and young adults should therefore be emphasized to reverse the obesity epidemic and thereby avoid further increases in the burden of cancer attributed to excess body fatness.
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Affiliation(s)
- K Hidayat
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - X Du
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, China
| | - B-M Shi
- Department of Endocrinology and Metabolism, The First Affiliated Hospital of Soochow University, Suzhou, China
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