|
1
|
Chiu HM, Matsuda T. Adopting Non-invasive Approaches into Precision Colorectal Cancer Screening. Dig Dis Sci 2025; 70:1616-1624. [PMID: 39516436 DOI: 10.1007/s10620-024-08696-z] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2024] [Accepted: 10/14/2024] [Indexed: 11/16/2024]
Abstract
Effective screening is essential to reducing CRC incidence and mortality by detecting the disease at early stages and identifying non-invasive precursors. While colonoscopy remains the most sensitive modality to visualize and remove neoplastic lesions thereby reducing CRC and the related death, its high cost and invasive nature limit its widespread use. The fecal immunochemical test (FIT), which offers a non-invasive alternative with higher public acceptance and comparable cost-effectiveness to colonoscopy, has become the preferred screening method in many regions. Newer non-invasive tests, such as multitarget stool DNA or RNA tests, have shown improved sensitivity for CRC and advanced adenomas, although their high costs and lower specificity present challenges for large-scale implementation. Blood-based circulating cell-free DNA test also offer promise but still require optimization to be cost-effective. The heterogeneity of the screening population further complicates the effectiveness of CRC screening programs. Variations in non-communicable disease risk factors, such as metabolic syndrome, lifestyle habits, and comorbidities, can significantly influence CRC risk and screening outcomes. Moreover, diverse screening behaviors, including inconsistent adherence to recommended screening intervals and the interchangeable use of different screening modalities, add complexity to achieving uniform effectiveness across populations. This variability underscores the need for personalized screening strategies that consider individual risk profiles and screening behaviors, as well as the application of cutting-edge technologies such as big data analytics, artificial intelligence, and digital twin approaches to evaluate its effectiveness. This article reviews the current CRC screening strategies, the advantages of non-invasive methods, and the potential of fecal hemoglobin concentration, to tailor screening intervals and improve risk stratification. It also discusses the emerging role of real-world data and advanced technologies in enhancing CRC screening accuracy and effectiveness, particularly in complex real-world scenarios where traditional methods may fall short. Before novel non-invasive approaches, such as ctDNA tests or polygenic risk scores, are validated and proven cost-effective, exploring the clinical utility of FIT and its quantitative measurement in both screening and surveillance by integrating real-world clinical big data seems a feasible direction for achieving sustained development in population screening.
Collapse
Affiliation(s)
- Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, No. 7, Chung-Shan South Road, Taipei, Taiwan.
| | - Takahisa Matsuda
- Division of Gastroenterology and Hepatology, Toho University Omori Medical Center, Tokyo, Japan
| |
Collapse
|
|
2
|
Nazarzadeh M, Copland E, Smith Byrne K, Canoy D, Bidel Z, Woodward M, Yang Q, McKay J, Mälarstig A, Hedman ÅK, Chalmers J, Teo KK, Pepine CJ, Davis BR, Kjeldsen SE, Sundström J, Rahimi K. Blood Pressure Lowering and Risk of Cancer: Individual Participant-Level Data Meta-Analysis and Mendelian Randomization Studies. JACC CardioOncol 2025:S2666-0873(25)00131-0. [PMID: 40366326 DOI: 10.1016/j.jaccao.2025.03.005] [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: 12/19/2024] [Revised: 03/14/2025] [Accepted: 03/17/2025] [Indexed: 05/15/2025] Open
Abstract
BACKGROUND Pharmacologic blood pressure (BP) lowering is typically a lifelong treatment, and both clinicians and patients may have concerns about the long-term use of antihypertensive agents and the risk for cancer. However, evidence from randomized controlled trials (RCTs) regarding the effect of long-term pharmacologic BP lowering on the risk for new-onset cancer is limited, with most knowledge derived from observational studies. OBJECTIVES The aim of this study was to assess whether long-term BP lowering affects the risk for new-onset cancer, cause-specific cancer death, and selected site-specific cancers. METHODS Individual-level data from 42 RCTs were pooled using a one-stage individual participant data meta-analysis. The primary outcome was incident cancer of all types, and secondary outcomes were cause-specific cancer death and selected site-specific cancers. Prespecified subgroup analyses were conducted to assess the heterogeneity of the BP-lowering effect by baseline variables and over follow-up time. Cox proportional hazards regression, stratified by trial, was used for the statistical analysis. For site-specific cancers, analyses were complemented with Mendelian randomization, using naturally randomized genetic variants associated with BP lowering to mimic the design of a long-term RCT. RESULTS Data from 314,016 randomly allocated participants without known cancer at baseline were analyzed. Over a median follow-up of 4 years (Q1-Q3: 3-5 years), 17,954 participants (5.7%) developed cancer, and 4,878 (1.5%) died of cancer. In the individual participant data meta-analysis, no associations were found between reductions in systolic or diastolic BP and cancer risk (HR per 5 mm Hg reduction in systolic BP: 1.03 [95% CI: 0.99-1.06]; HR per 3 mm Hg reduction in diastolic BP: 1.03 [95% CI: 0.98-1.07]). No changes in relative risk for incident cancer were observed over follow-up time, nor was there evidence of heterogeneity in treatment effects across baseline subgroups. No effect on cause-specific cancer death was found. For site-specific cancers, no evidence of an effect was observed, except a possible link with lung cancer risk (HR for systolic BP reduction: 1.17; 99.5% CI: 1.02-1.32). Mendelian randomization studies showed no association between systolic or diastolic BP reduction and site-specific cancers, including overall lung cancer and its subtypes. CONCLUSIONS Randomized data analysis provided no evidence to indicate that pharmacologic BP lowering has a substantial impact, either increasing or decreasing, on the risk for incident cancer, cause-specific cancer death, or selected site-specific cancers.
Collapse
Affiliation(s)
- Milad Nazarzadeh
- Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - Emma Copland
- Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom; National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
| | - Karl Smith Byrne
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, United Kingdom
| | - Dexter Canoy
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, United Kingdom
| | - Zeinab Bidel
- Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - Mark Woodward
- The George Institute for Global Health, University of New South Wales, Sydney, Australia; The George Institute for Global Health, School of Public Health, Imperial College London, London, United Kingdom
| | - Qianqian Yang
- Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom
| | - James McKay
- Genomic Epidemiology Branch, International Agency for Research on Cancer, Lyon, France
| | - Anders Mälarstig
- Discovery Network, Pfizer Worldwide Research and Development, Stockholm, Sweden; Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - Åsa K Hedman
- Discovery Network, Pfizer Worldwide Research and Development, Stockholm, Sweden; Department of Medicine, Karolinska Institute, Stockholm, Sweden
| | - John Chalmers
- The George Institute for Global Health, University of New South Wales, Sydney, Australia
| | - Koon K Teo
- Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, Ontario, Canada
| | - Carl J Pepine
- College of Medicine, University of Florida, Gainesville, Florida, USA
| | - Barry R Davis
- School of Public Health, The University of Texas, Houston, Texas, USA
| | - Sverre E Kjeldsen
- Department of Cardiology, University of Oslo, Ullevaal Hospital, Oslo, Norway
| | - Johan Sundström
- The George Institute for Global Health, University of New South Wales, Sydney, Australia; Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden
| | - Kazem Rahimi
- Deep Medicine, Oxford Martin School, University of Oxford, Oxford, United Kingdom; Nuffield Department of Women's and Reproductive Health, University of Oxford, Oxford, United Kingdom; National Institute for Health and Care Research Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom.
| |
Collapse
|
|
3
|
Jia X, Hu HQ. Research progress of MUC family in esophageal mucosal barrier of gastroesophageal reflux disease. Scand J Gastroenterol 2025; 60:375-385. [PMID: 40104877 DOI: 10.1080/00365521.2025.2479566] [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: 10/20/2024] [Revised: 02/11/2025] [Accepted: 03/10/2025] [Indexed: 03/20/2025]
Abstract
Gastroesophageal reflux disease (GERD) is a prevalent chronic digestive disorder with a rising incidence rate, profoundly affecting patients' quality of life. The condition is marked by recurrent episodes of acid reflux and heartburn, which can compromise the esophageal mucosal barrier and trigger inflammatory responses in the esophagus. Mucins (MUC), essential components of the mucus gel layer, play a vital role in protecting the esophageal mucosa and may serve as potential biomarkers for GERD diagnosis and treatment. This review provides a comprehensive overview of the MUC family's structure, types, and physiological functions, highlighting their significance in maintaining the esophageal mucosal barrier. By exploring the role of MUC in GERD, this paper aims to contribute to a deeper understanding of the disease's pathophysiological mechanisms and inform advancements in its diagnosis and treatment.
Collapse
Affiliation(s)
- Xue Jia
- Department of Endoscopic Center, Peking University Cancer Hospital (lnner Mongolia Campus), Hohhot, China
| | - Hai-Qing Hu
- Department of Endoscopic Center, Peking University Cancer Hospital (lnner Mongolia Campus), Hohhot, China
| |
Collapse
|
|
4
|
Lin F, Hu W, Yang C, Cheng B, Chen H, Li J, Zhu H, Zhang H, Yuan X, Ren X, Hong X, Tang X. Associations of combined lifestyle and metabolic risks with cancer incidence in the UK biobank study. BMC Cancer 2025; 25:547. [PMID: 40140964 PMCID: PMC11948676 DOI: 10.1186/s12885-025-13955-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2024] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
BACKGROUND Although metabolic syndrome (MetS) is associated with an increased risk of various cancers, the combined impact of MetS and healthy lifestyle factors (HLF) on cancer risk is unclear. This study aimed to investigate the independent and combined effects of MetS and HLF on the risk of 16 site-specific cancers in a large community-based cohort. METHODS A total of 289,557 participants in the UK Biobank were analyzed. MetS was defined using a combination of metabolic factors, while HLF scores were evaluated based on lifestyle behaviors, such as smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models were used to investigate the relationship between MetS or HLF and cancer risk, adjusting for age, sex, ethnicity, education level, family history of cancer, and the Townsend Deprivation Index (TDI). RESULTS During a median follow-up of 11.69 years, 11,190 individuals developed cancer. MetS was associated with an increased risk of 9 cancers in men and 7 cancers in women. Compared with participants with unfavorable lifestyles, regardless of metabolic status, HLF was significantly associated with decreased risk of overall cancer (without MetS: HR: 0.812; 95% CI: 0.745-0.886 for intermediate lifestyle and HR: 0.757; 95% CI: 0.669-0.855 for favorable lifestyle; with MetS: HR: 0.702; 95% CI: 0.572-0.862 for favorable lifestyle) and oesophagus, stomach, liver, lung, bronchus, trachea cancers in men and of lung, bronchus, trachea cancers in women. Our analysis demonstrated that the protective association between HLF and reduced cancer risk was confined to subgroups without MetS. Specifically, this association was observed for cancers of the lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, bladder, and lymphoid leukemia in men, and for overall cancer in women(HR: 0.917; 95% CI: 0.862-0.975 for intermediate lifestyle and HR: 0.875; 95% CI: 0.817-0.938 for favorable lifestyle). CONCLUSION MetS elevates risks for multiple cancers, while adopting a healthy lifestyle reduces risks of oesophagus, stomach, and lung, bronchus, trachea cancers in men and lung, bronchus, trachea cancer in women, regardless of metabolic status. However, MetS counteracts lifestyle-mediated protection against specific cancers-including lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, and bladder cancers in men, as well as pancreas and breast cancers in women. These findings underscore the necessity to develop metabolic status-stratified management strategies and implement proactive prevention of MetS.
Collapse
Affiliation(s)
- Feng Lin
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Wen Hu
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Chenfenglin Yang
- Department of Hepatobiliary Surgery, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Binglin Cheng
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Hongfan Chen
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Jiaxin Li
- Department of Obstetrics & Gynecology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, China
| | - Hanrui Zhu
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Haixiang Zhang
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Xiang Yuan
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China
| | - Xianyue Ren
- Guangdong Provincial Key Laboratory of Stomatology, Guanghua School of Stomatology, Hospital of Stomatology, Sun Yat-sen University, Guangzhou, China
| | - Xiaohong Hong
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China.
| | - Xinran Tang
- Department of Radiation Oncology, Southern Medical University Nanfang Hospital, Guangzhou, Guangdong, China.
| |
Collapse
|
|
5
|
Zhang X, Xu Z, Shang L, Yang Q, Ye H, Liu H, Zou Y, Lu Y, Zheng Z, Li M, Wang P, Zhu J. Global burden of colorectal cancer attributable to metabolic risks from 1990 to 2021, with predictions to 2046. BMC Cancer 2025; 25:228. [PMID: 39930395 PMCID: PMC11809015 DOI: 10.1186/s12885-025-13643-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 02/04/2025] [Indexed: 02/14/2025] Open
Abstract
BACKGROUND Metabolic risks are significant factors associated with colorectal cancer. This study aimed to assess global, regional and national burden for CRC attributable to metabolic risks from 1990 to 2021 and to predict mortality by 2046. METHODS Data from the Global Burden of Disease Study 2021 were used to quantify deaths, disability-adjusted life years (DALYs), and age-standardized rates of CRC due to metabolic risk factors, disaggregated by sex, age, region, country/territory, and sociodemographic index (SDI). The average annual percentage change (AAPC) was used to analyze temporal trends from 1990 to 2021. Metabolic risks include high fasting plasma glucose (FPG) and high body mass index (BMI). Future mortality trends up to 2046 were forecast using age-period-cohort models. RESULTS Globally, CRC deaths attributable to metabolic risks increased 2.47-fold, rising from 73,443 in 1990 to 181,689 in 2021. The global age-standardized mortality rates (ASMRs) and age-standardized rates of DALYs (ASDRs) of CRC attributable to high FPG and ASDRs attributable to high BMI increased from 1990 to 2021. The ASMRs and ASDRs of males was higher than that of females, with increasing trends. Central Europe had the highest ASMRs and ASDRs of CRC attributable to metabolic risks in 2021. Most regions and countries showed increasing trends in ASMR and ASDR for CRC due to metabolic risks, with Andean Latin America, Southeast Asia, and Cabo Verde increasing the most. High-SDI regions had the largest burden of CRC attributable to metabolic risks, while burden of other SDI regions have been significantly increased. A positive association was observed between SDI and age-standardized rates (ASMR: RFPG = 0.803, RBMI = 0.752; ASDR: RFPG = 0.812, RBMI = 0.756). By 2046, the ASMR of CRC attributable to high FPG was projected to remain stable and the ASMR due to high BMI was expected to see a slightly increase. CONCLUSION Colorectal cancer deaths and DALYs attributable to metabolic risk factors remain high, particularly in males and high-SDI regions. Further researches into the metabolic mechanisms of CRC and effective treatment strategies are needed.
Collapse
Affiliation(s)
- Xiaoyue Zhang
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
| | - Ziqing Xu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Lin Shang
- Department of Science and Technology of Henan Province, Zhengzhou, Henan Province, 450008, China
| | - Qian Yang
- Prenatal Diagnosis Center, The Third Affiliated Hospital of Zhengzhou University/Maternal and Child Health Hospital of Henan Province, Zhengzhou, Henan Province, 450052, China
| | - Hua Ye
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Haiyan Liu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Yuanlin Zou
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Yin Lu
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Zhong Zheng
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Meng Li
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China
| | - Peng Wang
- College of Public Health, Zhengzhou University, Zhengzhou, Henan Province, 450001, China.
- Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
| | - Jicun Zhu
- Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, China.
| |
Collapse
|
|
6
|
Xiao Y, Du X, Wang T, Liu D, You H, Wang H, Liang H, Ba Z, Liu Y, Ren Y, Zeng J, Yang W, Wu S, Yuan J. Serum Lipid Biomarkers and the Risk of Gastrointestinal Cancers in a Chinese Population: The Kailuan Prospective Study. Cancer Med 2025; 14:e70654. [PMID: 39912426 PMCID: PMC11799922 DOI: 10.1002/cam4.70654] [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: 05/18/2024] [Revised: 12/25/2024] [Accepted: 01/25/2025] [Indexed: 02/07/2025] Open
Abstract
BACKGROUND Current evidence on relationships between serum lipid biomarkers and the risk of gastrointestinal cancers remains controversial, with no consensus reached. METHODS We conducted a prospective cohort study within the Kailuan Cohort wherein 88,225 individuals with baseline information on triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was followed from 2006 to 2021 for the incidence of esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC). Cox proportional hazards models and restricted cubic spline (RCS) analysis were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS Increased EC risk was associated with high HDL-C levels (HRQ4vs.Q1 = 2.50, 95% CI: 1.57-3.98), while a U-shaped relationship between HDL-C and EC risk was revealed in the RCS analysis (poverall ≤ 0.0001, pnonlinear = 0.02). No robust association was identified between lipid biomarkers and GC risk. In multivariable analysis, increased CRC risk was positively associated with high TC levels (HRQ4vs.Q1 = 1.42, 95% CI: 1.11-1.83, ptrend = 0.03), dose-responsely negatively associated with LDL-C levels over quartiles (HRQ2vs.Q1 = 0.83, 95% CI: 0.66-1.02; HRQ3vs.Q1 = 0.86, 95% CI: 0.69-1.07; HRQ4vs.Q1 = 0.68, 95% CI: 0.53-0.86, ptrend = 0.02), and showed a diminished negative association with HDL-C levels over quartiles (HRQ2vs.Q1 = 0.75, 95% CI: 0.60-0.94; HRQ3vs.Q1 = 0.76, 95% CI: 0.61-0.95; HRQ4vs.Q1 = 0.91, 95% CI 0.74-1.13, ptrend = 0.02). The subsequent RCS analysis revealed a linear negative relationship of LDL-C (poverall = 0.004, pnonlinear = 0.67) and a U-shaped relationship of HDL-C (poverall = 0.05, pnonlinear = 0.02) with CRC risk. Competitive risk analysis and sensitivity analysis confirmed the stability of our results. CONCLUSION We observed a U-shaped relationship regarding HDL-C levels with EC and CRC risk, and a linear inverse relationship between LDL-C levels and CRC risk. Relevant serum lipid levels should be properly managed in high-risk individuals of certain gastrointestinal cancers.
Collapse
Affiliation(s)
- Ying Xiao
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Xin Du
- Department of CardiologyKailuan General HospitalTangshanChina
| | - Tianjie Wang
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Dong Liu
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Hongzhao You
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Hao Wang
- Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina
| | - Hanyang Liang
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Zhengqing Ba
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Yilu Liu
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Yu Ren
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Jinghan Zeng
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Weixian Yang
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| | - Shouling Wu
- Department of CardiologyKailuan General HospitalTangshanChina
| | - Jiansong Yuan
- Fuwai HospitalChinese Academy of Medical Sciences and Peking Union Medical College, National Center for Cardiovascular DiseasesBeijingChina
| |
Collapse
|
|
7
|
Sundaram S, Lamichhane R, Cecchetti A, Murughiyan U, Sundaram U. Risk of Colorectal Cancer among Patients with One or Multiple Metabolic Syndrome Components. Cancers (Basel) 2024; 16:3350. [PMID: 39409969 PMCID: PMC11482601 DOI: 10.3390/cancers16193350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/06/2024] [Revised: 09/20/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Background/Objectives: Dysfunctions of metabolic syndrome (MetS) have been identified as a significant risk factor for colorectal cancer (CRC). However, current colon cancer guidelines do not classify patients with MetS as high risk, thereby leaving these individuals vulnerable. Consequently, we explored the relationship between MetS, its individual components, and the development of CRC in a cohort of patients with MetS to assess the necessity for CRC screening in these individuals. Methods: This study included patients ages 18 and older that received a service from the Marshall-Health (MH) practice plan, Cabell-Huntington Hospital (CHH), MU/JCESOM's Edwards Comprehensive Cancer Center (ECCC), or the University of Kentucky HealthCare (UKHC) system between 2010 and 2018. We implemented log-binomial regression models to assess the individual and collective effects of MetS components after adjusting other CRC risk factors. Results: Given that CRC prevalence increases in the older population (aged 65 years and above), and that multiple components of MetS are observed within the same population, we analyzed the concurrent impact of all MetS components on CRC. Log-binomial regression models were implemented to assess the risk of CRC due to MetS components after adjusting other risk factors. Conclusions: We identified specific components that markedly increased CRC risk, suggesting that individuals with these components should be prioritized for early screening. These findings could significantly influence early CRC screening protocols, with the ultimate aim to reduce mortality associated with the disease.
Collapse
Affiliation(s)
- Shanmuga Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Rajan Lamichhane
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Alfred Cecchetti
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Usha Murughiyan
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| | - Uma Sundaram
- Department of Clinical and Translational Sciences, Joan C. Edwards School of Medicine, Marshall University, 1600 Medical Center Drive, Huntington, WV 25701, USA
| |
Collapse
|
|
8
|
Miranda BCJ, Tustumi F, Nakamura ET, Shimanoe VH, Kikawa D, Waisberg J. Obesity and Colorectal Cancer: A Narrative Review. MEDICINA (KAUNAS, LITHUANIA) 2024; 60:1218. [PMID: 39202500 PMCID: PMC11355959 DOI: 10.3390/medicina60081218] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 06/20/2024] [Revised: 07/21/2024] [Accepted: 07/24/2024] [Indexed: 09/03/2024]
Abstract
Background and Objectives: Cancer is a multicausal disease, and environmental, cultural, socioeconomic, lifestyle, and genetic factors can influence the risk of developing cancer. Colorectal cancer (CRC) stands as the third most common cancer globally. Some countries have observed a rise in the incidence of CRC, especially among young people. This increase is associated with lifestyle changes over the last few decades, including changes in diet patterns, a sedentary lifestyle, and obesity. Currently, obesity and overweight account for approximately 39% of the world's population and increase the risk of overall mortality of certain cancer types. This study aims to conduct a literature review examining the association between obesity and CRC. Materials and Methods: This narrative review explored the pathophysiological mechanisms, treatment strategies, and challenges related to obesity and CRC. Results: Several studies have established a clear causal relationship between obesity and CRC, showing that individuals with morbid obesity are at a higher risk of developing colorectal cancer. The adipose tissue, particularly the visceral, secretes proinflammatory cytokines, such as TNF-alpha, interleukin-6, and C-reactive protein. Chronic inflammation is closely linked to cancer initiation and progression, with a complex interplay of molecular mechanisms underlying this association. Obesity can complicate the treatment of CRC due to several factors, reducing the therapeutic effectiveness and increasing the risk for adverse events during treatment. Dietary modification, calorie restriction, and other types of weight-control strategies can reduce the risk of CRC development and improve treatment outcomes. Conclusions: Obesity is intricately linked to CRC development and progression, making it a crucial target for intervention, whether through diet therapy, physical exercises, medical therapy, or bariatric surgery.
Collapse
Affiliation(s)
- Bárbara Cristina Jardim Miranda
- Department of Surgery, Instituto de Assistência Médica ao Servidor Público Estadual—IAMSPE, Sao Paulo 04029-000, SP, Brazil
- Department of Surgery, Faculdade de Medicina do ABC—FMABC, Santo Andre 09060-870, SP, Brazil
| | - Francisco Tustumi
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
- Department of Health Sciences, Sociedade Beneficente Israelita Brasileira Albert Einstein, Sao Paulo 05652-900, SP, Brazil
| | - Eric Toshiyuki Nakamura
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Victor Haruo Shimanoe
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Daniel Kikawa
- Department of Gastroenterology, Faculty of Medicine, Universidade de São Paulo—USP, Sao Paulo 14040-903, SP, Brazil
| | - Jaques Waisberg
- Department of Surgery, Instituto de Assistência Médica ao Servidor Público Estadual—IAMSPE, Sao Paulo 04029-000, SP, Brazil
- Department of Surgery, Faculdade de Medicina do ABC—FMABC, Santo Andre 09060-870, SP, Brazil
| |
Collapse
|
|
9
|
Wang Z, Chen R, Zhang L, Chen Y, Li J, Li S, Xu L, Hu Y, Bai Y. Association between metabolic syndrome and the risk of colorectal cancer: a prospective study in China. Eur J Cancer Prev 2024; 33:347-354. [PMID: 38375832 DOI: 10.1097/cej.0000000000000863] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/21/2024]
Abstract
OBJECTIVE To evaluate the correlation between metabolic syndrome (MetS) and its components on the incidence of colorectal cancer (CRC) based on data from Jinchang Cohort. METHODS This is a large prospective cohort study. Between 2011 and 2020, a total of 43 516 individuals from Jinchang Cohort were included for this study. Hazard ratios (HRs) with 95% confidence intervals (CIs) for CRC according to MetS were calculated with the Cox proportional hazard models. The restricted cubic spine models with four knots were conducted to fit the dose-response relationships. RESULTS MetS was associated with increased risk of CRC (n = 141; HR: 1.64, 95% CI: 1.15-2.33) after adjusting for confounding factors (age, sex, education level, family history of CRC, smoking index and alcohol index). Participants with hyperglycemia had a significantly higher risk of developing incident CRC (HR: 1.70; 95% CI: 1.19-2.43). The positive association between MetS and CRC was observed in males (HR: 1.76; 95% CI: 1.17-2.63), but not in females (HR: 1.24; 95% CI: 0.59-2.64). Furthermore, linear dose-response relationship was found between fasting plasma glucose (FPG) and CRC risk in males ( Poverall < 0.05, Pnon-linear = 0.35). When stratified by smoke and drink, MetS was found to increase the incidence of CRC only in the smoke (HR: 2.07, 95% CI: 1.35-3.18) and drink (HR: 2.93, 95% CI: 1.51-5.69) groups. CONCLUSION MetS was associated with a higher risk of CRC incidence. Hyperglycemia lended strong support to the role of MetS in new-onset CRC, especially in males. Other components of MetS were not found to be associated with increased risk of CRC.
Collapse
Affiliation(s)
- Zhongge Wang
- Department of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, 199 Donggang West Street, Lanzhou, Gansu, China
| | | | | | | | | | | | | | | | | |
Collapse
|
|
10
|
Yuan C, Shu X, Hu Z, Jie Z. Genetic prediction of the relationship between metabolic syndrome and colorectal cancer risk: a Mendelian randomization study. Diabetol Metab Syndr 2024; 16:109. [PMID: 38773583 PMCID: PMC11110320 DOI: 10.1186/s13098-024-01351-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/26/2024] [Accepted: 05/15/2024] [Indexed: 05/24/2024] Open
Abstract
BACKGROUND Despite a growing body of observational studies indicating a potential link between metabolic syndrome and colorectal cancer, a definitive causal relationship has yet to be established. This study aimed to elucidate the causal relationship between metabolic syndrome and colorectal cancer through Mendelian randomization. METHODS We screened for instrumental variables associated with metabolic syndrome and its diagnostic components and with colorectal cancer through the use of a genome-wide association study database, and conducted a preliminary Mendelian randomization analysis. To corroborate the dependability of our conclusions, an additional dataset was used for replication analysis in a Mendelian randomization method, which was further integrated with a meta-analysis. RESULTS Preliminary analysis using the inverse variance weighted method revealed positive correlations between metabolic syndrome (OR [95% CI] = 1.37[1.15-1.63], P = 5.02 × 10-4) and waist circumference (OR [95% CI] = 1.39[1.21-1.61], P = 7.38 × 10-6) and the risk of colorectal cancer. Replication analysis also revealed the same results: metabolic syndrome (OR [95% CI] = 1.24[1.02-1.51], P = 0.030) and waist circumference (OR [95% CI] = 1.23[1.05-1.45], P = 0.013). The meta-analysis results further confirmed the associations between metabolic syndrome (OR [95% CI] = 1.31[1.15-1.49], P < 0.001) and waist circumference (OR [95% CI] = 1.32[1.18-1.47], P < 0.001) and colorectal cancer. CONCLUSION Our study indicated that metabolic syndrome increases the risk of CRC, particularly in patients with abdominal obesity.
Collapse
Affiliation(s)
- Chendong Yuan
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Xufeng Shu
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Zhenzhen Hu
- Department of Anesthesiology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China
| | - Zhigang Jie
- Department of General Surgery, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
- Medical Innovation Center, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006, Jiangxi, China.
| |
Collapse
|
|
11
|
Düzköylü Y, Demircioğlu MK, Kılavuz H, Sari S. The Relationship Between Serum Lipids and the Formation of Colorectal Polyps. Cureus 2024; 16:e57511. [PMID: 38706995 PMCID: PMC11066730 DOI: 10.7759/cureus.57511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/03/2024] [Indexed: 05/07/2024] Open
Abstract
BACKGROUND AND AIMS Obesity, metabolic syndrome, and hyperlipidemia are known as risk factors for colorectal tumors. Colorectal polyps are accepted as potential precursors of colorectal cancer (CRC). This study was designed to clarify the association between the levels of serum lipids and the presence of colorectal polyps. METHODS This study was conducted at Basaksehir Cam and Sakura City Hospital, Gastroenterological Surgery Clinic, Istanbul, Turkey. We retrospectively analyzed patients who underwent colonoscopy with serum lipid profile within one month for a one-year period. Groups were analyzed in terms of the correlation between hyperlipidemia and the formation of polyps. The study group was also evaluated in terms of the polyp type, localization, and number. RESULTS Among 453 patients, females were 248 and males were 211, with a mean age of 56.7. The study and control groups involved 259 and 194 patients, respectively. The age and serum levels of low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) were found to be statistically significant in terms of polyp presence and number (p < 0.05). CONCLUSION Colorectal polyps are well-known precursors of CRC. We found that the combination of elevated serum levels of low-density lipoprotein cholesterol, total cholesterol, and triglycerides may be a risk predictor for the presence of colorectal polyps, which can be advantageous in cancer screening.
Collapse
Affiliation(s)
- Yiğit Düzköylü
- Gastroenterological Surgery, Başakşehir Çam and Sakura City Hospital, İstanbul, TUR
| | | | - Hüseyin Kılavuz
- General Surgery, Başakşehir Çam and Sakura City Hospital, İstanbul, TUR
| | - Serkan Sari
- General Surgery, Başakşehir Çam and Sakura City Hospital, İstanbul, TUR
| |
Collapse
|
|
12
|
Son M, Moon SY, Koh M, Kang Y, Lee JY. Association between Surrogate Markers of Insulin Resistance and the Incidence of Colorectal Cancer in Korea: A Nationwide Population-Based Study. J Clin Med 2024; 13:1628. [PMID: 38541854 PMCID: PMC10971512 DOI: 10.3390/jcm13061628] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2024] [Revised: 03/08/2024] [Accepted: 03/11/2024] [Indexed: 05/31/2025] Open
Abstract
Background: Insulin resistance (IR) is assessed using surrogate markers such as the triglyceride-glucose (TyG) index, the triglyceride-to-high-density lipoprotein cholesterol (TG/HDL-C) ratio, and the metabolic score for IR (METS-IR). Limited studies investigated their association with colorectal cancer (CRC) incidence, and no research has been conducted on their association with the METS-IR. Method: This study used claims data from the Korean National Health Insurance Service, analyzing a cohort of 314,141 Koreans aged over 40 who participated in the National Health Screening Program from 2009 to 2010. The follow-up period was extended until 31 December 2019. Participants were divided into four groups based on quartiles (Q1-Q4) of the markers. Results: All surrogate markers of IR had sequentially statistically lower disease-free probabilities from Q1 to Q4. The Cox proportional hazard model demonstrated statistically significant positive associations between CRC incidence and Q3 and Q4 of the TyG index, as well as Q3 and Q4 of the TG/HDL-C ratio and Q4 of the METS-IR. The constrained cubic spline method revealed a nonlinear, positive dose-response relationship between the TyG index and the METS-IR in relation to CRC incidence. Conclusions: In conclusion, the TyG index, TG/HDL-C ratio, and METS-IR were positively correlated with CRC incidence in Koreans.
Collapse
Affiliation(s)
- Minkook Son
- Department of Physiology, Dong-A University College of Medicine, Busan 49201, Republic of Korea;
- Department of Data Sciences Convergence, Dong-A University Interdisciplinary Program, Busan 49201, Republic of Korea
| | - Sang Yi Moon
- Division of Gastroenterology, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea; (S.Y.M.); (M.K.); (Y.K.)
| | - Myeongseok Koh
- Division of Gastroenterology, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea; (S.Y.M.); (M.K.); (Y.K.)
| | - Yeowool Kang
- Division of Gastroenterology, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea; (S.Y.M.); (M.K.); (Y.K.)
| | - Jong Yoon Lee
- Division of Gastroenterology, Department of Internal Medicine, Dong-A University College of Medicine, Busan 49201, Republic of Korea; (S.Y.M.); (M.K.); (Y.K.)
| |
Collapse
|
|
13
|
Baban B, Eklund D, Tuerxun K, Alshamari M, Laviano A, Ljungqvist O, Särndahl E. Altered insulin sensitivity and immune function in patients with colorectal cancer. Clin Nutr ESPEN 2023; 58:193-200. [PMID: 38057005 DOI: 10.1016/j.clnesp.2023.09.917] [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: 08/24/2023] [Revised: 09/01/2023] [Accepted: 09/19/2023] [Indexed: 12/08/2023]
Abstract
BACKGROUND & AIMS Insulin resistance and chronic inflammation have been reported in patients with cancer. However, many of the underlying mechanisms and associations are yet to be unveiled. We examined both the level of insulin sensitivity and markers of inflammation in patients with colorectal cancer for comparison to controls. METHODS Clinical exploratory study of patients with colorectal cancer (n = 20) and matched controls (n = 10). Insulin sensitivity was quantified using the hyperinsulinemic normoglycemic clamp and blood samples were taken for quantification of several key, both intra- and extracellular, inflammatory markers. We analysed the differences in these parameters between the two groups. RESULTS Patients exhibited both insulin resistance (M-value, patients median (Mdn) 4.57 interquartile range (IQR) 3.49-5.75; controls Mdn 5.79 (IQR 5.20-6.81), p = 0.049), as well as increased plasma levels of the pro-inflammatory cytokines IL-1β (patients Mdn 0.48 (IQR 0.33-0.58); controls Mdn 0.36 (IQR 0.29-0.42), p = 0.02) and IL-6 (patients Mdn 3.21 (IQR 2.31-4.93); controls Mdn 2.16 (IQR 1.50-2.65), p = 0.02). The latter is present despite an almost two to three fold decrease (p < 0.01) in caspase-1 activity, a facilitating enzyme of IL-1β production, within circulating immune cells. CONCLUSION Patients with colorectal cancer displayed insulin resistance and higher levels of plasma IL-1β and IL-6, in comparison to matched healthy controls. The finding of a seemingly disconnect between inflammasome (caspase-1) activity and plasma levels of key pro-inflammatory cytokines in cancer patients may suggest that, in parallel to dysregulated immune cells, tumour-driven inflammatory pathways also are in effect.
Collapse
Affiliation(s)
- Bayar Baban
- Department of Surgery, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden.
| | - Daniel Eklund
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden; Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden
| | - Kedeye Tuerxun
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden; Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden
| | - Muhammed Alshamari
- School of Medical Sciences, Department of Radiology, Örebro University & Örebro University Hospital, SE-701 85 Örebro, Sweden
| | - Alessandro Laviano
- Department of Translational and Precision Medicine, Sapienza University, Rome, Italy
| | - Olle Ljungqvist
- Department of Surgery, School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden
| | - Eva Särndahl
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden; Inflammatory Response and Infection Susceptibility Centre (iRiSC), Faculty of Medicine and Health, Örebro University, SE-701 82 Örebro, Sweden
| |
Collapse
|
|
14
|
Zhu C, Mao C, Cai W, Zheng J, Yang H, You T, Chen J, Yu Y, Shen X, Li L. The effect of metabolic syndrome on postoperative complications and long-term survival of patients with colorectal cancer. Front Oncol 2023; 13:1036458. [PMID: 37434983 PMCID: PMC10332656 DOI: 10.3389/fonc.2023.1036458] [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: 09/04/2022] [Accepted: 06/09/2023] [Indexed: 07/13/2023] Open
Abstract
Background Metabolic syndrome (MetS) is associated with poor prognosis in many cancers. However, the relationship between metabolic syndrome and overall survival (OS) in patients with colorectal cancer (CRC) remains unclear. We aimed to comprehensively analyze whether MetS could affect postoperative complications and long-term survival in patients with CRC. Methods We included patients who underwent CRC resection at our center between January 2016 and December 2018. Bias was reduced through propensity score matching analysis. Patients with CRC were divided into the MetS and non-MetS groups based on whether they had MetS. Univariate and multivariate analyses were used to identify risk factors affecting OS. Results We included 268 patients; among them, 120 were included for further analysis after propensity score matching. There were no significant between-group differences in the clinicopathological features after matching. Compared with the non-MetS group, the MetS group had a shorter OS (P = 0.027); however, there was no significant between-group difference in postoperative complications. Multivariate analysis revealed that MetS (hazard ratio [HR] = 1.997, P = 0.042), tumor-node-metastasis stage (HR = 2.422, P = 0.003), and intestinal obstruction (HR = 2.761, P = 0.010) were independent risk factors for OS. Conclusions MetS affects the long-term survival of patients with CRC without affecting postoperative complications.
Collapse
Affiliation(s)
- Ce Zhu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Chenchen Mao
- Department of Microbiology and Immunology, School of Basic Medical Sciences, Institute of Molecular Virology and Immunology, Wenzhou Medical University, Zhejiang, China
| | - Wentao Cai
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jingwei Zheng
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hui Yang
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Tao You
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Jian Chen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Yaojun Yu
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xian Shen
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Liyi Li
- Department of Gastrointestinal Surgery, The Second Affiliated Hospital, Wenzhou Medical University, Wenzhou, Zhejiang, China
| |
Collapse
|
|
15
|
Association between the TyG index and TG/HDL-C ratio as insulin resistance markers and the risk of colorectal cancer. BMC Cancer 2022; 22:1007. [PMID: 36138391 PMCID: PMC9503258 DOI: 10.1186/s12885-022-10100-w] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Accepted: 09/19/2022] [Indexed: 11/24/2022] Open
Abstract
Background No previous prospective research has explored the association of the TyG (fasting triglyceride-glucose) index and TG/HDL-C ratio as insulin resistance markers with the risk of colorectal cancer (CRC) incidence in the Northern Chinese population. Methods In this prospective cohort study, we included 93,659 cancer-free participants with the measurements of TyG index and TG/HDL-C ratio. Participants were divided by the quartiles of the TyG index or TG/HDL-C ratio. The associations of TyG index, TG/HDL-C ratio, and their components with CRC risk were assessed using Cox proportional hazards regression models. Results During a median follow-up of 13.02 years, 593 incident CRC cases were identified. Compared with the lowest quartile of the TyG index (Q1), the risk of CRC was higher in persons in the third (Q3) and highest quartiles (Q4) of the TyG index, with corresponding multivariable-adjusted HRs (95% CI) of 1.36 (1.06, 1.76) and 1.50 (1.19, 1.91), respectively. The elevated risks of CRC incidence were observed in people in the second, third, and highest quartiles of the TG/HDL-C ratio groups, with corresponding multivariable-adjusted HRs (95% CI) of 1.33 (1.05, 1.70), 1.36 (1.07, 1.73) and 1.37 (1.07, 1.75), respectively. Conclusions Elevated TyG index and TG/HDL-C ratio were associated with a higher risk of developing CRC among adults in Northern China.
Collapse
|
|
16
|
Li L, Meng F, Xu D, Xu L, Qiu J, Shu X. Synergism between the metabolic syndrome components and cancer incidence: results from a prospective nested case-control study based on the China Health and Retirement Longitudinal Study (CHARLS). BMJ Open 2022; 12:e061362. [PMID: 36115664 PMCID: PMC9486362 DOI: 10.1136/bmjopen-2022-061362] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES Synergism between the metabolic syndrome (MetSyn) components and cancer incidence still remains inconclusive. We aimed to investigate the unique or joint role of MetSyn components in cancer onset. DESIGN We conducted a prospective nested case-control study based on the China Health and Retirement Longitudinal Study. SETTING An ongoing national representative longitudinal study included follow-up survey of people aged 45 years and older and their partners living in private households in China. PARTICIPANTS There were 17 708 individuals included at baseline. A total of 306 incident cancers was identified during the follow-up. For every case, we used incidence-density sampling to match three concurrent cancer-free controls by age, sex, and both duration and calendar time of follow-up. Exposure of interest was any MetSyn diagnosis at baseline. RESULTS We observed elevation in cancer risk associated with MetSyn in a significant way when the number of MetSyn components was over three (OR: 1.88; 95% CI: 1.19 to 2.97), or when components contained any of elevated triglycerides (OR: 1.61; 95% CI: 1.05 to 2.48), reduced high-density lipoprotein (HDL) cholesterol (OR: 2.33; 95% CI: 1.40 to 3.86) or elevated blood pressure (OR: 1.65; 95% CI: 1.04 to 2.59) after consistent multiple adjustments in different models. The highest cancer risk was in the female reproductive system and breast cancer (OR: 4.22; 95% CI: 1.62 to 10.95) followed by digestive system (OR: 1.67; 95% CI: 1.11 to 2.53). Sensitivity analyses showed similar results after first follow-up was excluded. However, any unique MetSyn component was not associated with increased cancer risk. Interestingly, the reduced HDL was observed to be widely associated with over twofold increased risk of cancer, only when together with other MetSyn components. CONCLUSION MetSyn components, in a collaborative manner rather than its unique component, were associated with elevated cancer risk. Not only obesity but even subtle metabolic disturbances may give rise to cancer.
Collapse
Affiliation(s)
- Lin Li
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People's Republic of China
| | - Fang Meng
- Institute of Systems Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People's Republic of China
- Suzhou Institute of Systems Medicine, Suzhou, China
| | - Dongkui Xu
- VIP Department, National Cancer Centre/National Clinical Research Centre for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China
| | - Lingkai Xu
- Department for Communicable Disease Control and Prevention, Suzhou Wuzhong Centre for Disease Prevention and Control, Suzhou, China
| | - Junlan Qiu
- Department of Oncology and Hematology, the Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Xiaochen Shu
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, People's Republic of China
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, People's Republic of China
| |
Collapse
|
|
17
|
Hsu SH, Syu DK, Chen YC, Liu CK, Sun CA, Chen M. The Association between Hypertriglyceridemia and Colorectal Cancer: A Long-Term Community Cohort Study in Taiwan. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19137804. [PMID: 35805464 PMCID: PMC9265720 DOI: 10.3390/ijerph19137804] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/01/2022] [Revised: 06/22/2022] [Accepted: 06/24/2022] [Indexed: 02/04/2023]
Abstract
(1) Background: Colorectal cancer (CRC) is the third most common malignancy and the second leading cause of cancer deaths worldwide. It often diagnosed at advanced stages, and with increasing incidence at younger generation. CRC poses a heavy financial burden and a huge public health challenge nowadays. Lipoproteins and serum lipids may have an influence on carcinogenesis by making oxidative stress, inflammation, and insulin resistance. Dyslipidemia plays a potential role in the risk of CRC. The purpose of this study is to use nationally representative samples to determine epidemiologic characteristics of CRC in the Taiwanese population, and to evaluate the associations between baseline levels of lipid profile and their effect on risk of colorectal cancer (CRC) comprehensively and quantitatively. The control of dyslipidemia in primary and secondary prevention may reduce the disease burden of CRC. (2) Methods: This is a nationwide long-term community-based prospective cohort study. Data were retrieved from the nationwide population-based Taiwanese Survey on Hypertension, Hyperglycemia and Hyperlipidemia (TwSHHH). Variables were estimated by the Cox proportional hazards model which was then further adjusted for age. We also calculated the relative ratios (RRs) of CRC for joint categories of serum cholesterol, triglyceride (TG), low-density lipoproteins cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) level, and to examine their combined effect and statistical interactions. (3) Results: Male, age, waist circumference, diabetes mellitus (DM), high TG, high cholesterol level, smoking history, and metabolic syndrome were proved to increase the risk of CRC. In addition, DM patients with a TG level ≥150 mg/dL and cholesterol ≥180 mg/dL had a 4.118-fold higher risk of CRC as compared with a TG level <150 mg/dL and cholesterol level <180 mg/dL, which was a significant difference (95% CI, 1.061−15.975; p = 0.0407). (4) Conclusions: Patients with DM should control TG and cholesterol level through diet, exercise, or taking medications more aggressively, not only for preventing cardiovascular disease, but also for first prevention of CRC. The study can be valuable for the clinicians and policy makers to implement more precisely goals about dyslipidemia management.
Collapse
Affiliation(s)
- Shu-Hua Hsu
- Department of Family Medicine, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan;
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
| | - De-Kai Syu
- Department of Orthopedics, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan;
| | - Yong-Chen Chen
- Master Program of Big Data in Biomedicine, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Data Science Center, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
| | - Chih-Kuang Liu
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Department of Urology, Fu Jen Catholic University Hospital, Fu Jen Catholic University, No. 69, Guizi Rd., Taishan Dist., New Taipei City 24352, Taiwan
| | - Chien-An Sun
- Data Science Center, College of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
- Department of Public Health, College of Medicine, Fu Jen Catholic University, Xinzhuang Dist., New Taipei City 24205, Taiwan
- Correspondence: (C.-A.S.); (M.C.)
| | - Mingchih Chen
- Graduate Institute of Business Administration, College of Management, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan;
- Artificial Intelligence Development Center, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei City 242062, Taiwan
- Correspondence: (C.-A.S.); (M.C.)
| |
Collapse
|
|
18
|
Yamaguchi T, Yoshida K, Murata M, Suwa K, Tsuneyama K, Matsuzaki K, Naganuma M. Smad3 Phospho-Isoform Signaling in Nonalcoholic Steatohepatitis. Int J Mol Sci 2022; 23:ijms23116270. [PMID: 35682957 PMCID: PMC9181097 DOI: 10.3390/ijms23116270] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 05/28/2022] [Accepted: 05/29/2022] [Indexed: 02/07/2023] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis with insulin resistance, oxidative stress, lipotoxicity, adipokine secretion by fat cells, endotoxins (lipopolysaccharides) released by gut microbiota, and endoplasmic reticulum stress. Together, these factors promote NAFLD progression from steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and eventually end-stage liver diseases in a proportion of cases. Hepatic fibrosis and carcinogenesis often progress together, sharing inflammatory pathways. However, NASH can lead to hepatocarcinogenesis with minimal inflammation or fibrosis. In such instances, insulin resistance, oxidative stress, and lipotoxicity can directly lead to liver carcinogenesis through genetic and epigenetic alterations. Transforming growth factor (TGF)-β signaling is implicated in hepatic fibrogenesis and carcinogenesis. TGF-β type I receptor (TβRI) and activated-Ras/c-Jun-N-terminal kinase (JNK) differentially phosphorylate the mediator Smad3 to create two phospho-isoforms: C-terminally phosphorylated Smad3 (pSmad3C) and linker-phosphorylated Smad3 (pSmad3L). TβRI/pSmad3C signaling terminates cell proliferation, while constitutive Ras activation and JNK-mediated pSmad3L promote hepatocyte proliferation and carcinogenesis. The pSmad3L signaling pathway also antagonizes cytostatic pSmad3C signaling. This review addresses TGF-β/Smad signaling in hepatic carcinogenesis complicating NASH. We also discuss Smad phospho-isoforms as biomarkers predicting HCC in NASH patients with or without cirrhosis.
Collapse
Affiliation(s)
- Takashi Yamaguchi
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
- Correspondence: ; Tel.: +81-72-804-0101; Fax: +81-72-804-2524
| | - Katsunori Yoshida
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
| | - Miki Murata
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
| | - Kanehiko Suwa
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
| | - Koichi Tsuneyama
- Department of Pathology & Laboratory Medicine, Institute of Biomedical Sciences, Tokushima University Graduate School, 3-18-15 Kuramoto, Tokushima 770-8503, Japan;
| | - Koichi Matsuzaki
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
| | - Makoto Naganuma
- Department of Gastroenterology and Hepatology, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, Osaka 573-1010, Japan; (K.Y.); (M.M.); (K.S.); (K.M.); (M.N.)
| |
Collapse
|
|
19
|
Feng Q, Tang LJ, Luo DH, Wang Y, Wu N, Chen H, Chen MX, Jiang L, Jin R. Metabolic Syndrome-Related Hyperuricemia is Associated with a Poorer Prognosis in Patients with Colorectal Cancer: A Multicenter Retrospective Study. Cancer Manag Res 2021; 13:8809-8819. [PMID: 34866939 PMCID: PMC8633709 DOI: 10.2147/cmar.s338783] [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: 09/13/2021] [Accepted: 11/12/2021] [Indexed: 12/23/2022] Open
Abstract
PURPOSE Hyperuricemia and metabolic syndrome (MetS) have been shown to correlate with prognosis in patients with malignant tumors. The present study evaluated the relationship between preoperative hyperuricemia and MetS in colorectal cancer (CRC) patients and analyzed the effect of this combination on prognosis within 5 years. PATIENTS AND METHODS The study enrolled patients who had undergone radical CRC resection at three independent medical centers from January 2014 to December 2016. Patients were preoperatively categorized into four groups, those with hyperuricemia alone (H), those with MetS alone (MS), those with MetS-related hyperuricemia (MSH), and those with neither condition (control [C] group). The disease-free survival (DFS) and overall survival (OS) rates of these four groups were compared. RESULTS The study population consisted of 1271 patients, with 114, 201, 101, and 855 patients categorized into the H, MS, MSH and C groups, respectively. Preoperative MetS was found to be significantly associated with hyperuricemia (P < 0.001). Multivariate Cox regression analysis showed that MetS-related hyperuricemia (hazard ratio [HR] = 2.728; P < 0.001) and MetS alone (HR = 1.631; P < 0.001) were independent predictors of death, whereas simple hyperuricemia was not (P > 0.1). Relative to the C group, the MSH group had the highest rate of tumor recurrence or metastasis (HR = 5.103, P < 0.001), followed by the MS (HR = 2.231, P < 0.001) group. In contrast, prognosis did not differ significantly in the H and C groups (P > 0.1). MetS was significantly associated with poor prognosis, with MetS-related hyperuricemia resulting in a significantly poorer prognosis. In contrast, hyperuricemia alone had no effect on the long-term prognosis of CRC patients. CONCLUSION This study highlights the prognostic importance of MetS-related hyperuricemia on the survival of patients with CRC.
Collapse
Affiliation(s)
- Qian Feng
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Liang-Jie Tang
- NAFLD Research Center, Department of Hepatology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Ding-Hai Luo
- Department of Gastroenterology, Taizhou Hospital of Zhejiang Province, Taizhou, 317000, People’s Republic of China
| | - Ying Wang
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Nan Wu
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Hao Chen
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Meng-Xia Chen
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Lei Jiang
- Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| | - Rong Jin
- Department of Gastroenterology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
- Department of Epidemiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of China
| |
Collapse
|
|
20
|
Tran TT, Gunathilake M, Lee J, Kim J. Association between metabolic syndrome and its components and incident colorectal cancer in a prospective cohort study. Cancer 2021; 128:1230-1241. [PMID: 34762301 DOI: 10.1002/cncr.34027] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2021] [Revised: 10/26/2021] [Accepted: 10/27/2021] [Indexed: 01/20/2023]
Abstract
BACKGROUND Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, reports concerning the association between MetS and colorectal cancer (CRC) have been inconsistent. This study investigated whether MetS, its components, and the number of components increase the risk of CRC. METHODS This was a prospective cohort study of 41,837 participants recruited from August 2002 to December 2014 from the National Cancer Center in South Korea. The participants were followed until December 2017 to identify incident CRC cases. The participants underwent laboratory tests at the baseline. Additionally, a self-administered questionnaire collected information concerning lifestyle and general characteristics at the baseline. A Cox proportional hazards model was used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) to explore the association between MetS and its components and CRC risk after adjustments for confounding variables. RESULTS In total, 128 incident CRC cases were identified during the follow-up period. An increased CRC risk was found among participants with MetS (HR, 1.63; 95% CI, 1.08-2.44). Additionally, elevated blood pressure (HR, 1.50; 95% CI, 1.05-2.15) and a high fasting glucose level (HR, 1.80; 95% CI, 1.23-2.63) were associated with an elevated risk of CRC. Notably, an increased risk was identified among participants with abdominal obesity coexisting with another component of MetS. CONCLUSIONS These results suggest that MetS is a risk factor for CRC. Greater emphasis should be placed on the importance of CRC screening among individuals with abdominal obesity coexisting with another component of MetS. LAY SUMMARY Colorectal cancer (CRC) ranks as the third most common cancer type in terms of incidence. Metabolic syndrome (MetS) has been identified as a contributor to cancer development. However, the association between MetS and CRC remains controversial because of a lack of consistent findings in previous studies. In this study, the National Cholesterol Education Program's Adult Treatment Panel III guidelines are used for the diagnosis of MetS. MetS is found to be a predictor of CRC. Additionally, the importance of CRC screening among individuals with 2 components of MetS should be emphasized.
Collapse
Affiliation(s)
- Tao Thi Tran
- Department of Cancer Control and Population Health, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Madhawa Gunathilake
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang-Si, Korea
| |
Collapse
|
|
21
|
Li Q, Liu F, Tang Y, Lee S, Lang C, Bai L, Xia Y. The Distribution of Cardiovascular-Related Comorbidities in Different Adult-Onset Cancers and Related Risk Factors: Analysis of 10 Year Retrospective Data. Front Cardiovasc Med 2021; 8:695454. [PMID: 34595215 PMCID: PMC8476781 DOI: 10.3389/fcvm.2021.695454] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 08/19/2021] [Indexed: 12/25/2022] Open
Abstract
Introduction: Understanding the epidemiology of cardiovascular disease (CVD) related comorbidity is a key strategy for improving the outcomes of patients with cancer. Therefore, this study aimed to assess the distribution of cardiovascular comorbidities and cardiovascular risk factors (CVRF) among five cancer sites. Methods: This is a single-centered, cross-sectional study performed in Dalian, China. Between 2008 and 2018, all newly diagnosed cancer in the First Affiliated Hospital of Dalian Medical University, China were screened. Clinical data were extracted from a comprehensive electronic health record system. Results: 35861 patients with lung, colorectal, gastric, breast, and thyroid cancer were collected retrospectively. The most prevalent CVDs in descending order were hypertension (21.9%), followed by coronary heart disease (6.5%), atrial fibrillation (2.9%), and heart failure (1%). The prevalence of hypertension significantly varies between lung (21.3%), colorectal (27.3%), gastric (22.5%), breast (16.7%), and thyroid cancer (22.4%) (P < 0.001). CVRF varies with cancer sites. Age, sex, total cholesterol, triglyceride, low-density lipoprotein cholesterol, systolic blood pressure, smoking, alcohol use, and diabetes mellitus (DM) are common risk factors associated with CVD at different cancer sites. The association between DM and presence of CVD was strong in breast (odds ratio [OR] = 4.472, 95% confidence interval [CI]: 3.075-6.504, P < 0.001), lung (OR = 3.943; 95% CI: 3.270-4.754, P < 0.001), colorectal (OR = 3.049; 95% CI: 2.326-3.996, P < 0.001), and gastric (OR = 2.508; 95% CI: 1.927-3.264, P < 0.001) cancer. Conclusion: Cancer patients had a significant burden of CVD and increased CVRF. The prevalence of CVRF and CVD comorbidity differ for cancer types. DM remains significantly associated with CVD at different cancer sites except for thyroid cancer.
Collapse
Affiliation(s)
- Qingsong Li
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Fei Liu
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Yuqi Tang
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| | - Sharen Lee
- Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, SAR China
| | - Chao Lang
- Yidu Cloud Technology, Ltd., Beijing, China
| | - Lan Bai
- Yidu Cloud Technology, Ltd., Beijing, China
| | - Yunlong Xia
- Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, China
| |
Collapse
|
|
22
|
Kwon RJ, Park EJ, Lee SY, Lee Y, Hwang C, Kim C, Cho YH. Expression and prognostic significance of Niemann-Pick C1-Like 1 in colorectal cancer: a retrospective cohort study. Lipids Health Dis 2021; 20:104. [PMID: 34511128 PMCID: PMC8436523 DOI: 10.1186/s12944-021-01539-0] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Accepted: 08/31/2021] [Indexed: 11/10/2022] Open
Abstract
BACKGROUND Colorectal cancer (CRC) is a malignancy of the large intestine, whose development and prognosis have been demonstrated to be associated with altered lipid metabolism. High cholesterol intake is associated with an increased risk of CRC, and elevated serum cholesterol levels are known to be correlated with risk of developing CRC. Niemann-Pick C1-Like 1 (NPC1L1), a target of ezetimibe, plays an essential role in the absorption of intestinal cholesterol. However, whether the altered expression of NPC1L1 affects CRC development and prognosis is currently unknown. METHODS Data corresponding to patients with CRC were obtained from The Cancer Genome Atlas (TCAG). Datasets from the Genome Data Analysis Center (GDAC) platform were analyzed to compare the expression of NPC1L1 in normal and CRC tissues using the Mann-Whitney U test and chi-square test. Further, the datasets from the Gene Expression Omnibus (GEO) database were analyzed. The log-rank test and multivariate Cox proportional hazard regression analysis were performed to determine whether NPC1L1 significantly affects the prognosis of CRC. RESULTS The expression of NPC1L1 was found to be upregulated in CRC and was significantly associated with the N and pathological stages but not with the histological type, age, and sex. Increased NPC1L1 expression in CRC was related to poor patient survival, as evidenced by the Kaplan-Meier and multivariate regression analyses. CONCLUSIONS As high expression of NPC1L1 was associated with CRC development, pathological stage, and prognosis, NPC1L1 can serve as an independent prognostic marker for CRC.
Collapse
Affiliation(s)
- Ryuk Jun Kwon
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Eun-Ju Park
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Sang Yeoup Lee
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Youngin Lee
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea
| | - Chungsu Hwang
- Department of Pathology, Pusan National University School of Medicine, 626-780, Yangsan, South Korea
| | - Choongrak Kim
- Department of Statistics, Pusan National University, 609-735, Busan, South Korea
| | - Young Hye Cho
- Family Medicine Clinic and Research Institute of Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Beomeo-ri, Mulgeum-eup, 50612, Yangsan, Gyeongsangnam-do, South Korea.
| |
Collapse
|
|
23
|
Chiu HM. Obesity, metabolic derangement, and the risk of colorectal neoplasm. J Gastroenterol Hepatol 2021; 36:1731-1732. [PMID: 34263484 DOI: 10.1111/jgh.15584] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/09/2022]
Affiliation(s)
- Han-Mo Chiu
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| |
Collapse
|
|
24
|
Crudele L, Piccinin E, Moschetta A. Visceral Adiposity and Cancer: Role in Pathogenesis and Prognosis. Nutrients 2021; 13:2101. [PMID: 34205356 PMCID: PMC8234141 DOI: 10.3390/nu13062101] [Citation(s) in RCA: 54] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Revised: 06/14/2021] [Accepted: 06/16/2021] [Indexed: 12/11/2022] Open
Abstract
The prevalence of being overweight and obese has been expanded dramatically in recent years worldwide. Obesity usually occurs when the energetic introit overtakes energy expenditure from metabolic and physical activity, leading to fat accumulation mainly in the visceral depots. Excessive fat accumulation represents a risk factor for many chronic diseases, including cancer. Adiposity, chronic low-grade inflammation, and hyperinsulinemia are essential factors of obesity that also play a crucial role in tumor onset. In recent years, several strategies have been pointed toward boundary fat accumulation, thus limiting the burden of cancer attributable to obesity. While remodeling fat via adipocytes browning seems a tempting prospect, lifestyle interventions still represent the main pathway to prevent cancer and enhance the efficacy of treatments. Specifically, the Mediterranean Diet stands out as one of the best dietary approaches to curtail visceral adiposity and, therefore, cancer risk. In this Review, the close relationship between obesity and cancer has been investigated, highlighting the biological mechanisms at the basis of this link. Finally, strategies to remodel fat, including browning and lifestyle interventions, have been taken into consideration as a major perspective to limit excess body weight and tumor onset.
Collapse
Affiliation(s)
- Lucilla Crudele
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- Department of Biomedical Sciences and Human Oncology, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Elena Piccinin
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Antonio Moschetta
- Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, 70124 Bari, Italy; (L.C.); (E.P.)
- INBB, National Institute for Biostructures and Biosystems, 00136 Rome, Italy
- National Cancer Center, IRCCS Istituto Tumori Giovanni Paolo II, 70124 Bari, Italy
| |
Collapse
|
|
25
|
Ku MS, Chiu SYH, Chien KL, Lee YC, Chen SLS, Chen CD. Gender difference in metabolic syndrome and incident colorectal adenoma: A prospective observational study (KCIS No.42). Medicine (Baltimore) 2021; 100:e26121. [PMID: 34087861 PMCID: PMC8183717 DOI: 10.1097/md.0000000000026121] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 04/18/2021] [Accepted: 05/10/2021] [Indexed: 01/04/2023] Open
Abstract
ABSTRACT This community-based study aimed to elucidate whether there is a gender difference in the effect of metabolic syndrome (MetS) and its individual components on an elevated risk for incident colorectal adenoma.A prospective cohort study was conducted by enrolling 59,767 subjects aged 40 years or older between 2001 and 2009 in Keelung, Taiwan, to test this hypothesis, excluding those with a prior history of colorectal cancer and those with colorectal cancer diagnosed at the first screening. Cox proportional hazards regression models were used to assess the effect of MetS in terms of a dichotomous classification, each individual component and the number of components for males and females.Colorectal adenoma was present in 2.7% (n = 652) of male participants and 1.1% (n = 403) of female participants. The prevalence rate of MetS was 26.7% and 23.3% for males and females, respectively. The effect of MetS on colorectal adenoma was statistically significant and similar for the 2 genders, with an adjusted hazard ratio (aHR) of 1.33 (95% CI: 1.13-1.58) in males and 1.33 (95% CI: 1.06-1.66) in females after adjustment for confounders. However, MetS led to higher risk of advanced colorectal adenoma in men than in women. Regarding the effect of each component of MetS on colorectal adenoma, abnormal waist circumference and hypertriglyceridemia led to an elevated risk of colorectal adenoma in both genders. A rising risk of colorectal adenoma among females was noted in those with a moderately higher level of glycemia (100-125 mg/dL, aHR = 1.44, 95% CI: 1.12-1.85). Hypertriglyceridemia and high blood pressure were associated with an increased risk of advance colorectal adenoma in males.Both male and female subjects with MetS had a higher risk of colorectal adenoma. The contributions from individual components of MetS varied by gender. These findings suggest that the possible risk reduction of colorectal adenoma through metabolic syndrome-based lifestyle modifications may differ between genders.
Collapse
Affiliation(s)
- Mei-Sheng Ku
- Institute of Environmental and Occupational Health Science, College of Public Health, National Taiwan University, Taipei
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management, College of Management, Chang Gung University, Taoyuan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung
| | - Kuo-Liong Chien
- Institute of Epidemiology and Preventive Medicine, College of Public School
- Department of Internal Medicine, College of Medicine
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University
| | - Yi-Chia Lee
- Institute of Epidemiology and Preventive Medicine, College of Public School
- Department of Internal Medicine, College of Medicine
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University
- Department of Medical Research, National Taiwan University Hospital
| | - Sam Li-Sheng Chen
- School of Oral Hygiene, College of Oral Medicine
- TMU Research Center of Cancer Translational Medicine, Taipei Medical University, Taipei
| | - Chih-Dao Chen
- Department of Family Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| |
Collapse
|
|
26
|
Zhao M, Wang H, Chen J, Xi Y, Wang F, Huo C, Li W, Chu Y, Xu P, Huang Q, Bu S. Expression of long non-coding RNA H19 in colorectal cancer patients with type 2 diabetes. Arch Physiol Biochem 2021; 127:228-234. [PMID: 31232113 DOI: 10.1080/13813455.2019.1628068] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2019] [Accepted: 05/31/2019] [Indexed: 12/24/2022]
Abstract
The aim of this study was to explore the lncRNAs expression in colorectal cancer (CRC) patients with type 2 diabetes (T2DM) and evaluate the diagnostic value of lncRNAs expression in CRC patients with T2DM. The present study was conducted on two cohorts with CRC patients. The tissues levels of lncRNAs were measured by real-time PCR analysis. The results showed that H19 and MALAT1 expression were higher in CRC tissues than in normal colorectal mucosa (p = 1.59 × 10-6 and p = 6.95 × 10-9, respectively), whereas lincRNA-p21 showed lower expression in CRC tissues (p = 1.10 × 10-4). Logistic regression analysis results indicated that the expression of H19 was significantly lower in CRC patients with T2DM compared with CRC patients without T2DM (p = .032). H19 expression in CRC group without T2DM was significantly associated with hypertension (p = .040). Additionally, the area under the receiver operating characteristic curve of H19 was 0.672 of the group CRC with T2DM, which suggests that H19 could be a useful biomarker and predictive targets for diagnosis of T2DM in CRC patients.
Collapse
Affiliation(s)
- Ming Zhao
- Department of Medical Services, The Affiliated Hospital of Medical School of Ningbo University, Ningbo, China
| | - Hantao Wang
- Department of Colorectal Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Jingbo Chen
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yang Xi
- Diabetes Research Center, Medical School, Ningbo University, Ningbo, China
| | - Fuyan Wang
- Diabetes Research Center, Medical School, Ningbo University, Ningbo, China
| | - Cuilan Huo
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Wenwen Li
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Yudong Chu
- Department of Nephrology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China
- The Second Section within Ninghai Second Hospital, Ningbo, China
| | - Pengjie Xu
- Department of Nephrology, Ningbo Medical Center Lihuili Eastern Hospital, Ningbo, China
- The Second Section within Ninghai Second Hospital, Ningbo, China
| | - Qin Huang
- Department of Endocrinology, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Shizhong Bu
- Diabetes Research Center, Medical School, Ningbo University, Ningbo, China
| |
Collapse
|
|
27
|
Zhang C, Cheng Y, Luo D, Wang J, Liu J, Luo Y, Zhou W, Zhuo Z, Guo K, Zeng R, Yang J, Sha W, Chen H. Association between cardiovascular risk factors and colorectal cancer: A systematic review and meta-analysis of prospective cohort studies. EClinicalMedicine 2021; 34:100794. [PMID: 33997727 PMCID: PMC8102710 DOI: 10.1016/j.eclinm.2021.100794] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 02/22/2021] [Accepted: 02/24/2021] [Indexed: 02/08/2023] Open
Abstract
BACKGROUND Emerging data have suggested colorectal cancer (CRC) often coexists with cardiovascular diseases, but whether cardiovascular risk factors play a role in CRC remains unclear. We performed a systematic review and meta-analysis to better illustrate the associations between cardiovascular risk factors and CRC. METHODS We searched EMBASE, MEDLINE and Web of Science databases from inception up to June 14, 2020. Prospective cohort studies were included if they evaluated the association between at least one of cardiovascular risk factors and CRC incidence, containing sufficient data to obtain relative risk (RR) and 95% confidence interval (CI). We performed separate meta-analyses for each cardiovascular risk factor using random-effect model. PROSPERO registration number: CRD42020175537. FINDINGS Data from 84 studies, reporting 52, 348, 827 individuals and 384, 973 incident cases were included in the analysis. Overall, the risk of CRC was 1.31(95% CI, 1.21-1.42) for obesity, 1.14 (95% CI, 1.09-1.20) for per 5 kg/m2 increase in body mass index, 1.18 (95% CI, 1.14-1.23) for former smoker, 1.20 (95% CI, 1.11-1.30) for current smoker, 1.25 (95% CI, 1.16-1.35) for diabetes, 1.07 (95% CI, 1.02-1.12) for hypertension. The summary RRs of CRC for the highest versus lowest quartiles of total cholesterol, triglyceride, low-density lipoprotein were 1.12 (95% CI, 1.03-1.22), 1.18 (95% CI, 1.04-1.35), 0.85 (95% CI, 0.62-1.17) respectively and the pooled RR for the lowest versus highest quartile of high-density lipoprotein was 1.14 (95% CI, 1.02-1.28). INTERPRETATION Unfavorable cardiovascular risk factors are associated with increased risk of CRC, which may provide novel insight into the screening strategies of CRC in patient with these risk factors.
Collapse
Affiliation(s)
- Chen Zhang
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Department of Gastroenterology, Affiliated South China Hospital, Southern Medical University (Guangdong Provincial People's Hospital), Guangzhou 510080, China
| | - Yunjiu Cheng
- Department of Cardiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China
| | - Dongling Luo
- Department of Cardiology, The Eighth Affiliated Hospital, Sun Yat-Sen University, Shenzhen 518033, China
| | - Jinghua Wang
- Department of Hematology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Jianhua Liu
- Department of Oncology, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Yujun Luo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Shantou University Medical College, Shantou, Guangdong 515041, China
| | - Weijie Zhou
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Zewei Zhuo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Kehang Guo
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Ruijie Zeng
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| | - Jun Yang
- Institute for Environmental and Climate Research, Jinan University, Guangzhou 511443, China
| | - Weihong Sha
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
- Department of Gastroenterology, Affiliated South China Hospital, Southern Medical University (Guangdong Provincial People's Hospital), Guangzhou 510080, China
| | - Hao Chen
- Department of Gastroenterology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou 510080, China
| |
Collapse
|
|
28
|
Wang C, Zou Y, Pan C, Shao L, Ding Z, Zhang Y, Ye J, Li P, Ren Y, Zhu C. Prognostic significance of chemokines CCL11 and CCL5 modulated by low-density lipoprotein cholesterol in colon cancer patients with normal body mass index. ANNALS OF TRANSLATIONAL MEDICINE 2021; 9:202. [PMID: 33708829 PMCID: PMC7940920 DOI: 10.21037/atm-20-1604] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Background Many studies have shown an elevated level of cholesterol in colon tumors as compared to normal tissue. Obesity and high low-density lipoprotein cholesterol (LDL-C) are known risk factors for colon cancer. However, the role of LDL-C in colon cancer patients with normal body mass index (BMI) remains elusive. Methods Levels of serum cholesterol and oxysterols were quantified by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) from 129 individuals with normal BMI, including 32 with solitary polyp, 36 with multiple polyps, and 31 with adenocarcinoma as well as 32 healthy controls. In vitro, colon cancer cells were treated with LDL-C and assayed for chemokines via RNA-Seq and mitochondrial morphology via transmission electron microscopy and immunofluorescence. Additionally, correlation analysis was performed between LDL-C-induced chemokines and the overall survival of colon cancer patients from the Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), and the Human Protein Atlas (HPA) database. Results The serum cholesterol level was significantly higher in colon adenocarcinoma patients with normal BMI than that in healthy controls (P<0.001). LDL-C potentiated colon cancer cell invasion and resistance to glucose-deprivation in vitro via chemokine-mediated signaling, mainly upregulation of CC chemokine ligand (CCL) 5 and downregulation of CCL 11. By analyzing the RNA expression data of colorectal cancer from TCGA, GTEx, and HPA, we demonstrated that the CCL5 level in colorectal adenocarcinoma tissues was significantly increased relative to adjacent normal tissues (P=0.01) while the CCL11 level was decreased (P=0.01). Both increased CCL5 and decreased CCL11 showed a negative correlation with the 5-year overall survival in tumor node metastasis (TNM) stage II colon cancer patients (P=0.0032, 0.026 for CCL5 and CCL11, respectively). Conclusions Our study supports the idea that LDL-C regulates the expression of CCL5 and CCL11 chemokines, which may have predictive values for survival in colon cancer patients with normal BMI, especially for patients in TNM stage II.
Collapse
Affiliation(s)
- Caihua Wang
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yi Zou
- Department of Pathology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chi Pan
- Department of Surgical Oncology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liming Shao
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zonghui Ding
- Department of Cancer Biology, Mayo Clinic Arizona, Scottsdale, Arizona, USA
| | - Yunzhu Zhang
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jun Ye
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Peiwei Li
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Yuezhong Ren
- Department of Endocrinology and Metabolism, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Chunpeng Zhu
- Department of Gastroenterology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| |
Collapse
|
|
29
|
Cancer patients with potential eligibility for vascular endothelial growth factor antagonists use have an increased risk for cardiovascular diseases comorbidities. J Hypertens 2021; 38:426-433. [PMID: 31584518 PMCID: PMC7012358 DOI: 10.1097/hjh.0000000000002277] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
Abstract
BACKGROUND Recent studies have reported the prevalence of cardiovascular diseases (CVDs) among cancer patients following the use of the vascular endothelial growth factor (VEGF) signaling inhibitors. However, data for patients with a history of cancer before active cancer treatment are lacking. This study aims to investigate the distribution of CVD-related comorbidities before cancer treatment in potential VEGF antagonists candidates. METHODS A total of 22 500 newly diagnosed cancer patients registered from 1 January 2011 to 31 December 2017 were included. Cancer patients with colorectal cancer (CRC), renal cell carcinoma (RCC), thyroid cancer, hepatocellular carcinoma (HCC), and lung cancer were selected. RESULTS Hypertension (HTN), coronary heart diseases, atrial fibrillation, and heart failure were top CVD comorbidities among studied cancers. HTN was the most prevalent CVD (26.0%). The prevalence of HTN in RCC, CRC (33.5 and 29.4% respectively) was significantly higher than that in HCC, lung cancer, and thyroid cancer patients (25.1, 24.5, and 23.1%, respectively). Among cancer patients with HTN, the majority of cancer patients fall in grade III (75.7%) and very high cardiovascular risk level (85.4%). Out of the 5847 HTN patients, 26% were not in antihypertensive use, and 34.2% failed to achieve the target blood pressure. CONCLUSION Cancer patients carry a high burden of CVD-related comorbidities before the application of VEGF antagonists. HTN is the most prevalent comorbid condition, and cancer patients with HTN constitute substantial cardiovascular risks and a higher co-prevalence of other CVDs.
Collapse
|
|
30
|
Xuan K, Zhao T, Sun C, Patel AS, Liu H, Chen X, Qu G, Sun Y. The association between hypertension and colorectal cancer: a meta-analysis of observational studies. Eur J Cancer Prev 2021; 30:84-96. [PMID: 32039929 DOI: 10.1097/cej.0000000000000578] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The relationship between hypertension and risk of colorectal cancer (CRC) is unclear. This meta-analysis aims to explore the association between them. Six databases were searched for studies published before August 2019. The pooled relative risk (RR) and 95% confidence intervals (CIs) were calculated to estimate the association between the hypertension and CRC risk. A total of 2841 potentially relevant articles were obtained, and 25 studies with a pooled 1.95 million participants were finally included in the meta-analysis. These results suggested a positive association between hypertension and risk of CRC with a pooled RR of 1.15 (95% CI: 1.08, 1.23). Male patients with hypertension had a 13% (95% CI: 1.06, 1.20) increased risk of CRC. The risk of colon cancer and rectal cancer in male patients was 1.17 (95% CI: 1.01, 1.36) and 1.35 (95% CI: 1.04, 1.74), respectively, while no association between hypertension and the risk of CRC in females was elucidated. This meta-analysis demonstrated that a positive association between hypertension and CRC exists, with male patients having a higher risk of developing CRC than female patients.
Collapse
Affiliation(s)
- Kun Xuan
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Tianming Zhao
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Chenyu Sun
- AMITA Health Saint Joseph Hospital Chicago
| | - Akash S Patel
- University of Illinois at Chicago College of Medicine, Chicago, Illinois, USA
| | - Haixia Liu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Xin Chen
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Guangbo Qu
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
| | - Yehuan Sun
- Department of Epidemiology and Health Statistics, School of Public Health, Anhui Medical University, Hefei, Anhui, China
- Center for Evidence-Based Practice, Anhui Medical University, Hefei, Anhui, China
| |
Collapse
|
|
31
|
Han F, Wu G, Zhang S, Zhang J, Zhao Y, Xu J. The association of Metabolic Syndrome and its Components with the Incidence and Survival of Colorectal Cancer: A Systematic Review and Meta-analysis. Int J Biol Sci 2021; 17:487-497. [PMID: 33613107 PMCID: PMC7893592 DOI: 10.7150/ijbs.52452] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2020] [Accepted: 11/13/2020] [Indexed: 12/22/2022] Open
Abstract
Background: This meta-analysis was aimed to quantitatively assess the associations of metabolic syndrome (MetS) and its components with colorectal cancer (CRC). Methods: PubMed, EMBASE and Web of Science databases were systematically searched for eligible studies. A total of 18 studies for CRC incidence and 12 studies for CRC mortality were identified. Results: MetS was associated with an increased risk of CRC incidence and mortality in male (RR: 1.28, 95 % CI 1.16-1.39, and 1.24, 1.18-1.31, respectively) and correlated with an increased risk of CRC incidence in female (RR: 1.21, 1.13-1.30), but not with CRC mortality in female. MetS increased the risk of cancer-specific mortality (RR: 1.72, 1.03-2.42), but not overall mortality. The risk estimates of CRC incidence changed little depending on age, sex, cancer site, the type of studies, ethnicity, publication year, or definition of MetS. As for CRC mortality, further stratified analyses indicated statistical significance in studies with assessing cancer-specific survival outcome, in male, a cohort design, ethnicity of non-Chinese or with definition of MetS as ≥ 3 metabolic abnormalities. Obesity and hyperglycemia are risk factors of CRC incidence in both male and female. Only dysglycemia is the risk factor for CRC mortality. Conclusions: MetS is associated with an increased risk of CRC incidence and cancer-specific mortality, but not overall mortality. In addition, MetS may increase the CRC mortality in male rather than in female. However, since most of the studies on CRC mortality were conducted in Chinese, further studies are needed to clarify this connection.
Collapse
Affiliation(s)
- Fei Han
- NHC Key Laboratory of Hormones and Development, Tianjin Key Laboratory of Metabolic Diseases, Chu Hsien-I Memorial Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300134, China
| | - Guanghai Wu
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Shuai Zhang
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Judong Zhang
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Yongjie Zhao
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| | - Jing Xu
- Department of General Surgery, Tianjin Union Medical Center, Tianjin 300121, China
| |
Collapse
|
|
32
|
Feng Q, Xu L, Li L, Qiu J, Huang Z, Jiang Y, Wen T, Lu S, Meng F, Shu X. Risk of Death in Colorectal Cancer Patients with Multi-morbidities of Metabolic Syndrome: A Retrospective Multicohort Analysis. Cancer Res Treat 2020; 53:714-723. [PMID: 33285055 PMCID: PMC8291199 DOI: 10.4143/crt.2020.481] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Accepted: 12/01/2020] [Indexed: 12/13/2022] Open
Abstract
Purpose The prevalence of multi-morbidities with colorectal cancer (CRC) is known to be increasing. Particularly prognosis of CRC patients co-diagnosed with metabolic syndrome (MetSyn) was largely unknown. We aimed to examine the death risk of CRC patients according to the multiple MetSyn morbidities. Materials and Methods We identified CRC patients with MetSyn from the electronic medical records (EMR) systems in five independent hospitals during 2006–2011. Information on deaths was jointly retrieved from EMR, cause of death registry and chronic disease surveillance as well as study-specific questionnaire. Cox proportional hazards regression was used to calculate the overall and CRC-specific hazards ratios (HR) comparing MetSyn CRC cohort with reference CRC cohort. Results A total of 682 CRC patients in MetSyn CRC cohort were identified from 24 months before CRC diagnosis to 1 month after. During a median follow-up of 92 months, we totally observed 584 deaths from CRC, 245 being in MetSyn cohort and 339 in reference cohort. Overall, MetSyn CRC cohort had an elevated risk of CRC-specific mortality (HR, 1.49; 95% confidence interval [CI], 1.07 to 1.90) and overall mortality (HR, 1.43; 95% CI, 1.09 to 1.84) compared to reference cohort after multiple adjustment. Stratified analyses showed higher mortality risk among women (HR, 1.87; 95% CI, 1.04 to 2.27) and specific components of MetSyn. Notably, the number of MetSyn components was observed to be significantly related to CRC prognosis. Conclusion Our findings supported that multi-morbidities of MetSyn associated with elevated death risk after CRC. MetSyn should be considered as an integrated medical condition more than its components in CRC prognostic management.
Collapse
Affiliation(s)
- Qingting Feng
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Lingkai Xu
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Lin Li
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China
| | - Junlan Qiu
- Department of Oncology and Hematology, the Affiliated Suzhou Science and Technology Town Hospital of Nanjing Medical University, Suzhou, China
| | - Ziwei Huang
- Department of Orthopaedics, Orthopaedic Institute, the First Affiliated Hospital, Soochow University, Suzhou, China
| | - Yiqing Jiang
- Department of General Surgery, Harrison International Peace Hospital, Hengshui, China
| | - Tao Wen
- Medical Research Centre, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
| | - Shun Lu
- Department of Radiation Oncology, Sichuan Cancer Hospital/Institute, University of Electronic Science and Technology of China, Chengdu, China
| | - Fang Meng
- Centre of Systems Medicine, Chinese Academy of Medical Sciences, Beijing, China.,Suzhou Institute of Systems Medicine, Suzhou, China
| | - Xiaochen Shu
- Department of Epidemiology, School of Public Health, Medical College of Soochow University, Suzhou, China.,Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Medical College of Soochow University, Suzhou, China
| |
Collapse
|
|
33
|
Kidoguchi S, Sugano N, Tokudome G, Yokoo T, Yano Y, Hatake K, Nishiyama A. New Concept of Onco-Hypertension and Future Perspectives. Hypertension 2020; 77:16-27. [PMID: 33222548 DOI: 10.1161/hypertensionaha.120.16044] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Owing to aging populations, the prevalence of hypertension and associated cardiovascular events has been increasing worldwide. The morbidity and mortality due to cancer have also been increasing with aging populations. Several small-molecule inhibitors have been used in cancer therapy, which have a positive impact on the prognosis and survival of patients with cancer. Consequently, the number of cancer survivors with hypertension has been rapidly increasing. Anticancer therapy, including vascular endothelial growth factor inhibitors, increases blood pressure. However, both clinical and laboratory evidence are lacking regarding optimal blood pressure control in patients with hypertension with cancer. Here, we propose the concept of onco-hypertension, which is an evolving subspecialty focused on the complex pathophysiology of hypertension and cancer. In this review, we highlight blood pressure changes in cancer, hypertension induced by anticancer therapy, and optimal blood pressure management in patients with hypertension with cancer. In addition, we discuss needed studies to further establish this new onco-hypertension concept.
Collapse
Affiliation(s)
- Satoshi Kidoguchi
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan (S.K., N.S., G.T., T.Y.).,Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan (S.K., A.N.)
| | - Naoki Sugano
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan (S.K., N.S., G.T., T.Y.)
| | - Gorou Tokudome
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan (S.K., N.S., G.T., T.Y.)
| | - Takashi Yokoo
- Division of Nephrology and Hypertension, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan (S.K., N.S., G.T., T.Y.)
| | - Yuichiro Yano
- Department of Family Medicine and Community Health, Duke University, Durham, NC (Y.Y.)
| | - Kiyohiko Hatake
- Department of Lymphoma/Hematologic Malignancy Center, Mita Hospital, International University of Health and Welfare, Tokyo, Japan (K.H.)
| | - Akira Nishiyama
- Department of Pharmacology, Faculty of Medicine, Kagawa University, Japan (S.K., A.N.)
| |
Collapse
|
|
34
|
Cho YK, Lee J, Kim HS, Park JY, Lee WJ, Kim YJ, Jung CH. Metabolic health is a determining factor for incident colorectal cancer in the obese population: A nationwide population-based cohort study. Cancer Med 2020; 10:220-229. [PMID: 33216467 PMCID: PMC7826459 DOI: 10.1002/cam4.3607] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2020] [Revised: 10/22/2020] [Accepted: 10/25/2020] [Indexed: 12/13/2022] Open
Abstract
Background The association of the risk of colorectal cancer (CRC) with obesity or obesity‐induced metabolic disturbances remains controversial. We assessed the association of metabolic health status with incident CRC among subjects with obesity. Methods This study included 319,397 subjects from the Korean National Health Insurance Service‐National Health Screening Cohort. Transitions in metabolic health status and obesity were examined during 2009–2010 and 2011–2012. We categorized subjects with obesity into four separate groups according to their dynamic metabolic health status: metabolically healthy obesity (MHO), MHO to metabolically unhealthy obesity (MUO), MUO to MHO, and stable MUO. Subjects were followed up from 2009 to 2015 for incident CRC. Results The stable MHO group showed no increased risk of incident CRC (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.83–1.14). However, the MHO to MUO group had a higher risk of incident CRC than the stable metabolically healthy nonobese (MHNO) group (HR, 1.34; 95% CI, 1.15–1.57). Among patients with MUO at baseline, those in the subgroup who transitioned to MHO group were not at increased risk of CRC (HR, 1.06; 95% CI, 0.91–1.25), whereas those who remained in the stable MUO group had a higher risk of incident CRC than those in the stable MHNO group (HR, 1.29; 95% CI, 1.19–1.41). Conclusions The transition of metabolic health was a determining factor for CRC among subjects with obesity. Hence, maintenance or recovery of metabolic health should be addressed to prevent CRC in individuals with obesity.
Collapse
Affiliation(s)
- Yun Kyung Cho
- Department of Internal Medicine, Hallym University Sacred Heart Hospital, Hallym University College of Medicine, Anyang, Republic of Korea
| | - Jiwoo Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Hwi Seung Kim
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Joong-Yeol Park
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Woo Je Lee
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Ye-Jee Kim
- Department of Clinical Epidemiology and Biostatistics, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Chang Hee Jung
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| |
Collapse
|
|
35
|
Liu B, Wen P, Gu X, Weng R, Liu S. Elevated serum triglyceride predicts recurrence of colorectal polyps in patients with advanced adenomas. Lipids Health Dis 2020; 19:211. [PMID: 32967679 PMCID: PMC7513493 DOI: 10.1186/s12944-020-01388-3] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2020] [Accepted: 09/15/2020] [Indexed: 12/19/2022] Open
Abstract
Background Recurrence of colorectal polyps is common and impacted by various factors. This study was performed to explore the association between lipid profiles and recurrence of colorectal polyps. Methods This study retrospectively analyzed the lipid profiles of 435 patients who underwent colonoscopy with removal of colorectal polyps and assessed recurrence of polyps by follow-up colonoscopy. Multivariate regression logistic analysis was used to evaluate the association between lipid profiles and polyp recurrence. Results During the 1.5-year follow-up, recurrence of colorectal polyps was observed in 135 of 435 patients (30.34%). Patients with recurrent polyps showed a higher level of triglycerides (P = 0.006) and lower levels of high-density lipoprotein cholesterol (P = 0.008) and apolipoprotein A1 (P = 0.033). The multivariate regression logistic model suggested that an elevated triglyceride level was an independent risk factor for polyp recurrence (odds ratio, 1.55; 95% confidence interval, 1.02–2.35; P = 0.039) in patients with advanced adenoma. Conclusions Lipid profiles are associated with recurrence of colorectal polyps. An elevated triglyceride level is an independent risk predictor of polyp recurrence in patients with advanced adenoma.
Collapse
Affiliation(s)
- Boying Liu
- Department of Gastroenterology, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China
| | - Pingwu Wen
- Department of Gastroenterology, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China
| | - Xiaodong Gu
- Research Experimental Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China
| | - Ruiqiang Weng
- Research Experimental Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China
| | - Sudong Liu
- Research Experimental Center, Meizhou People's Hospital (Huangtang Hospital), Meizhou Hospital Affiliated to Sun Yat-sen University, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China. .,Guangdong Provincial Key Laboratory of Precision Medicine and Clinical Translational Research of Hakka Population, No. 63 Huangtang Road, Meijiang District, Meizhou, 514031, P. R. China.
| |
Collapse
|
|
36
|
Chen XQ, Wu PW, Liu DH, Yan SJ, Shen XM, Yang LY. Prognostic significance of high triglyceride and apolipoprotein B levels in patients with stage III and high-risk stage II colorectal cancer undergoing curative surgery. Oncol Lett 2020; 20:705-714. [PMID: 32565996 PMCID: PMC7285852 DOI: 10.3892/ol.2020.11617] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 04/07/2020] [Indexed: 01/17/2023] Open
Abstract
Although epidemiologic studies suggest that dyslipidemia increases the risk of colorectal cancer (CRC), the prognostic value of blood lipid and apolipoprotein levels in CRC remains unclear. The aim of the present study was to investigate the impact of blood lipid and apolipoprotein levels on the prognosis of patients with stage III and high-risk stage II CRC undergoing curative surgery. Preoperative levels of total cholesterol, triglycerides (TG), high-density lipoprotein, low-density lipoprotein, very-low-density lipoprotein, apolipoprotein A1 and apolipoprotein B (APO-B) in patients with CRC undergoing surgery were evaluated. The cut-off values of these factors were determined by the maximal x2 method and were used to classify patients into two prognostic groups: Poor and good prognosis groups. The patients prognostic values were assessed using the Kaplan-Meier curve and Cox regression analysis. In addition, the impact of these parameters on the prognosis and their predictive accuracy were evaluated using nomograms and Harrells concordance index, respectively. In total, 246 patients were included in this evaluation. Based on the cut-off points for TG (1.53 mmol/l in men and 1.58 mmol/l in women) and APO-B (0.73 mmol/l in men and women), the present study determined that both TG and APO-B were predictors of disease-free survival (DFS) and overall survival (OS). Multivariate analysis demonstrated that high TG (men, ≥1.53 mmol/l; women, ≥1.58 mmol/l) and high APO-B (≥0.73 mmol/l) levels were significantly associated with decreased DFS and OS. Nomograms that included values for TG and APO-B levels demonstrated higher predictive accuracy compared with that of nomograms without these values. These results indicated that TG and APO-B levels may be good independent prognostic biomarkers after radical CRC surgery. Therefore, adjusting these parameters to moderate levels may be beneficial.
Collapse
Affiliation(s)
- Xiu-Qing Chen
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| | - Pei-Wen Wu
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| | - Dong-Hui Liu
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| | - Sun-Jie Yan
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| | - Xi-Mei Shen
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| | - Li-Yong Yang
- Department of Endocrinology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian 350005, P.R. China.,Diabetes Research Institute of Fujian Province, Fuzhou, Fujian 350005, P.R. China
| |
Collapse
|
|
37
|
Lee SH, Lee HA, Lee SS, Kim SE, Shim KN, Jung HK, Jung SA, Chang JH, Kwon K, Pyun WB, Joung B, Moon CM, Park J. Clinical impact of pre-hypertension on the risk of cancer in male and female subjects. Sci Rep 2020; 10:9974. [PMID: 32561792 PMCID: PMC7305195 DOI: 10.1038/s41598-020-66653-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2019] [Accepted: 05/19/2020] [Indexed: 12/16/2022] Open
Abstract
There are few studies assessing pre-hypertension and an impaired fasting glucose (IFG) and their combined effects on the cancer risk. We investigated the impact of pre-hypertension on cancer risk and IFG, and their combined effects on the cancer risk. This study included 371,762 subjects (≥40 years) who had never been diagnosed with hypertension, diabetes mellitus (DM), and cancer before. During a mean follow-up of 10.06 ± 1.86 years, 35,605 (9.58%) of the subjects developed cancer. In men only, cancer risk was significantly increased with an increase in the blood pressure (BP) (P for trend < 0.001), and were increased in the hypertension range, but not the pre-hypertension range. When analyzing the combination effect of BP and fasting glucose, cancer risks were serially increased with an increase in the fasting glucose in a dose-dependent manner, but not with an increase in BP. These results were more consistently significant in the never-smoker and non-alcohol drinking groups. However, in women, there was no significant difference. In conclusions, increased BP status or the fasting serum glucose level status were associated with cancer risk in men. Furthermore, the combination of both pre-hypertension and IFG also was associated with a cancer risk in men.
Collapse
Affiliation(s)
- Su Hwan Lee
- Division of Pulmonology, Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Hye Ah Lee
- Clinical Trial Center, Ewha Womans University Mokdong Hospital, Ewha Womans University, Seoul, Republic of Korea.,Department of Preventive Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Sean S Lee
- Program in Liberal Medical Education, The Warren Alpert Medical School, Brown University, Providence, United States
| | - Seong-Eun Kim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Ki-Nam Shim
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Hye-Kyung Jung
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Sung-Ae Jung
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Jung Hyun Chang
- Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Kihwan Kwon
- Division of Cardiology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Wook Bum Pyun
- Division of Cardiology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea
| | - Boyoung Joung
- Department of Cardiology, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Chang Mo Moon
- Division of Gastroenterology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea. .,Tissue Injury Defense Research Center, Ewha Womans University, Seoul, Republic of Korea.
| | - Junbeom Park
- Division of Cardiology, Department of Internal Medicine, College of Medicine, Ewha Womans University, Seoul, Republic of Korea.
| |
Collapse
|
|
38
|
Christakoudi S, Kakourou A, Markozannes G, Tzoulaki I, Weiderpass E, Brennan P, Gunter M, Dahm CC, Overvad K, Olsen A, Tjønneland A, Boutron-Ruault MC, Madika AL, Severi G, Katzke V, Kühn T, Bergmann MM, Boeing H, Karakatsani A, Martimianaki G, Thriskos P, Masala G, Sieri S, Panico S, Tumino R, Ricceri F, Agudo A, Redondo-Sánchez D, Colorado-Yohar SM, Mokoroa O, Melander O, Stocks T, Häggström C, Harlid S, Bueno-de-Mesquita B, van Gils CH, Vermeulen RC, Khaw KT, Wareham NJ, Tong TY, Freisling H, Johansson M, Lennon H, Aune D, Riboli E, Trichopoulos D, Trichopoulou A, Tsilidis KK. Blood pressure and risk of cancer in the European Prospective Investigation into Cancer and Nutrition. Int J Cancer 2020; 146:2680-2693. [PMID: 31319002 PMCID: PMC7115826 DOI: 10.1002/ijc.32576] [Citation(s) in RCA: 62] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Revised: 05/23/2019] [Accepted: 06/14/2019] [Indexed: 12/19/2022]
Abstract
Several studies have reported associations of hypertension with cancer, but not all results were conclusive. We examined the association of systolic (SBP) and diastolic (DBP) blood pressure with the development of incident cancer at all anatomical sites in the European Prospective Investigation into Cancer and Nutrition (EPIC). Hazard ratios (HRs) (95% confidence intervals) were estimated using multivariable Cox proportional hazards models, stratified by EPIC-participating center and age at recruitment, and adjusted for sex, education, smoking, body mass index, physical activity, diabetes and dietary (in women also reproductive) factors. The study included 307,318 men and women, with an average follow-up of 13.7 (standard deviation 4.4) years and 39,298 incident cancers. We confirmed the expected positive association with renal cell carcinoma: HR = 1.12 (1.08-1.17) per 10 mm Hg higher SBP and HR = 1.23 (1.14-1.32) for DBP. We additionally found positive associations for esophageal squamous cell carcinoma (SCC): HR = 1.16 (1.07-1.26) (SBP), HR = 1.31 (1.13-1.51) (DBP), weaker for head and neck cancers: HR = 1.08 (1.04-1.12) (SBP), HR = 1.09 (1.01-1.17) (DBP) and, similarly, for skin SCC, colon cancer, postmenopausal breast cancer and uterine adenocarcinoma (AC), but not for esophageal AC, lung SCC, lung AC or uterine endometroid cancer. We observed weak inverse associations of SBP with cervical SCC: HR = 0.91 (0.82-1.00) and lymphomas: HR = 0.97 (0.93-1.00). There were no consistent associations with cancers in other locations. Our results are largely compatible with published studies and support weak associations of blood pressure with cancers in specific locations and morphologies.
Collapse
Affiliation(s)
- Sofia Christakoudi
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- MRC Centre for Transplantation, King’s College London, Great Maze Pond, London SE1 9RT, United Kingdom
| | - Artemisia Kakourou
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Georgios Markozannes
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Ioanna Tzoulaki
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| | - Elisabete Weiderpass
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Paul Brennan
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Marc Gunter
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Christina C. Dahm
- Department of Public Health, Aarhus University, DK-8000, Aarhus, Denmark
| | - Kim Overvad
- Department of Public Health, Aarhus University, DK-8000, Aarhus, Denmark
- Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark
| | - Anja Olsen
- Diet, Genes and Environment, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark
| | - Anne Tjønneland
- Diet, Genes and Environment, Danish Cancer Society Research Center, DK-2100, Copenhagen, Denmark
- Department of Public Health, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Marie-Christine Boutron-Ruault
- Centre de recherche en Epidemiologie et Sante des Populations (CESP), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
| | - Anne-Laure Madika
- Centre de recherche en Epidemiologie et Sante des Populations (CESP), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
- Université Lille, CHU Lille, EA2694, Lille, France
| | - Gianluca Severi
- Centre de recherche en Epidemiologie et Sante des Populations (CESP), Fac. de médecine - Univ. Paris-Sud, Fac. de médecine - UVSQ, INSERM, Université Paris-Saclay, 94805, Villejuif, France
- Gustave Roussy, F-94805, Villejuif, France
| | - Verena Katzke
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Tilman Kühn
- Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany
| | - Manuela M. Bergmann
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Arthur-Scheunert-Allee 114-116, Nuthetal, Germany
| | - Heiner Boeing
- Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Arthur-Scheunert-Allee 114-116, Nuthetal, Germany
| | - Anna Karakatsani
- Hellenic Health Foundation, Athens, Greece
- 2 Pulmonary Medicine Department, School of Medicine, National and Kapodistrian University of Athens, “ATTIKON” University Hospital, Haidari, Greece
| | | | | | - Giovanna Masala
- Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network - ISPRO, Florence, Italy
| | - Sabina Sieri
- Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, 20133, Milano, Italy
| | - Salvatore Panico
- Dipartimento di Medicina Clinica e Chirurgia, Federico II University, Naples, Italy
| | - Rosario Tumino
- Cancer Registry and Histopathology Department, "M.P.Arezzo" Hospital, ASP Ragusa, Italy
| | - Fulvio Ricceri
- Department of Clinical and Biological Sciences, University of Turin, Italy
- Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco (TO), Italy
| | - Antonio Agudo
- Unit of Nutrition and Cancer. Cancer Epidemiology Research Program. Catalan Institute of Oncology-IDIBELL. L’Hospitalet de Llobregat, Barcelona, Spain
| | - Daniel Redondo-Sánchez
- Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA, Universidad de Granada. Granada, Spain
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
| | - Sandra M. Colorado-Yohar
- CIBER de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain
- Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain
- Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia
| | - Olatz Mokoroa
- Public Health Division of Gipuzkoa, BioDonostia Research Institute, San Sebastian, Spain
| | - Olle Melander
- Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden
| | - Tanja Stocks
- Department of Clinical Sciences Lund, Lund University, Lund, Sweden
| | - Christel Häggström
- Department of Biobank Research, Umeå University, Umeå, Sweden
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Sophia Harlid
- Department of Radiation Sciences, Umeå University, Umeå, Sweden
| | - Bas Bueno-de-Mesquita
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- Dept. for Determinants of Chronic Diseases (DCD), National Institute for Public Health and the Environment (RIVM), PO Box 1, 3720 BA Bilthoven, The Netherlands
- Department of Gastroenterology and Hepatology, University Medical Centre, Utrecht, The Netherlands
- Dept. of Social & Preventive Medicine, Faculty of Medicine, University of Malaya, Pantai Valley, 50603, Kuala Lumpur, Malaysia
| | - Carla H. van Gils
- Department of Epidemiology, Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, The Netherlands
| | - Roel C.H. Vermeulen
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- Environmental Epidemiology Group, Institute of Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands
- Public Health Department, University Medical Center, Utrecht, The Netherlands
| | - Kay-Tee Khaw
- University of Cambridge, School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge CB2 2QQ, United Kingdom
| | - Nicholas J. Wareham
- MRC Epidemiology Unit, Institute of Metabolic Science, School of Clinical Medicine, University of Cambridge, Cambridge CB2 0QQ, United Kingdom
| | - Tammy Y.N. Tong
- Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford. United Kingdom
| | - Heinz Freisling
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Mattias Johansson
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Hannah Lennon
- International Agency for Research on Cancer, World Health Organization, 69372 Lyon CEDEX 08, France
| | - Dagfinn Aune
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- Department of Nutrition, Bjørknes University College, Oslo, Norway
- Department of Endocrinology, Morbid Obesity and Preventive Medicine, Oslo University Hospital, Oslo, Norway
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
| | - Dimitrios Trichopoulos
- Hellenic Health Foundation, Athens, Greece
- Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
- Bureau of Epidemiologic Research, Academy of Athens, Athens, Greece
| | | | - Konstantinos K. Tsilidis
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, St Mary’s Campus, Norfolk place, London W2 1PG, United Kingdom
- Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina, Greece
| |
Collapse
|
|
39
|
Ramezankhani A, Azizi F, Hadaegh F. Sex-specific clustering of metabolic risk factors and cancer risk: a longitudinal study in Iran. Biol Sex Differ 2020; 11:21. [PMID: 32334634 PMCID: PMC7183600 DOI: 10.1186/s13293-020-00296-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 04/06/2020] [Indexed: 02/07/2023] Open
Abstract
Background Cancer is a major cause of death in low- and middle-income countries. A large number of studies have shown that some of the metabolic risk factors (MRFs) tend to cluster in individuals. We examined the synergistic effects of multiple MRFs and cancer risk among Iranian adults. Methods Among 8593 (3929 men) participants aged ≥ 30 years, the self-organizing map (SOM) was applied to clustering of four MRFs including high fasting plasma glucose (HFPG), high total cholesterol (HTC), high systolic blood pressure (HSBP), and high body mass index (HBMI). The Cox proportional hazards model was used to investigate the association between clusters with cancer incidence during a median of 14.0 years of follow-up. Results During the study period, 265 new cases of cancer were identified among participants at risk. The incidence density rate was 2.5 per 1000 person years in total population. About 32 and 40% of men and women, respectively, had three or four MRFs. We identified seven clusters of MRFs in both men and women. In both genders, MRFs were clustered in those with older age. Further, inverse associations were found between current smoking in men, and education level and passive smoking in women and clustering of MRFs. In men, a cluster with 100% HSBP and HBMI had the highest risk for overall cancer. While, among women, a cluster with 100% HFPG and 93% HBMI yielded the highest risk for cancer. The risk was decreased when HBMI accompanied by HTC. Conclusions Clustering patterns may reflect underlying link between MRFs and cancer and could potentially facilitate tailored health promotion interventions.
Collapse
Affiliation(s)
- Azra Ramezankhani
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Yemen Street, Shahid Chamran Highway, P.O. Box: 19395-4763, Tehran, Iran
| | - Fereidoun Azizi
- Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Farzad Hadaegh
- Prevention of Metabolic Disorders Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Yemen Street, Shahid Chamran Highway, P.O. Box: 19395-4763, Tehran, Iran.
| |
Collapse
|
|
40
|
Lee J, Lee KS, Kim H, Jeong H, Choi MJ, Yoo HW, Han TH, Lee H. The relationship between metabolic syndrome and the incidence of colorectal cancer. Environ Health Prev Med 2020; 25:6. [PMID: 32075578 PMCID: PMC7031951 DOI: 10.1186/s12199-020-00845-w] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2019] [Accepted: 02/12/2020] [Indexed: 12/20/2022] Open
Abstract
OBJECTIVES This study evaluated the incidence of colorectal cancer (CRC) according to the number of metabolic syndrome (MetS) components. METHODS Using health checkup and insurance claims data of 6,365,409 subjects, the occurrence of CRC according to stage of MetS by sex was determined from the date of the health checkup in 2009 until December 31, 2018. RESULTS Cumulative incidence rates (CIR) of CRC in men and women was 3.9 and 2.8 per 1000 (p < 0.001), respectively. CIR of CRC for the normal, pre-MetS, and MetS groups in men was 2.6, 3.9, and 5.5 per 1000 (p < 0.001) and CIR in women was 2.1, 2.9, and 4.5 per 1000 (p < 0.001), respectively. Compared with the normal group, the hazard ratio (HR) of CRC for the pre-MetS group was 1.25 (95% CI 1.17-1.33) in men and 1.09 (95% CI 1.02-1.17) in women, and the HR of CRC for the MetS group was 1.54 (95% CI 1.43-1.65) in men and 1.39 (95% CI 1.26-1.53) in women after adjustment. CONCLUSIONS We found that MetS is a risk factor for CRC in this study. Therefore, the prevention and active management of MetS would contribute to the prevention of CRC.
Collapse
Affiliation(s)
- JungHyun Lee
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Kun Sei Lee
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hyeongsu Kim
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hyoseon Jeong
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Min-Jung Choi
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Hai-Won Yoo
- Department of Preventive Medicine, School of Medicine, Konkuk University, Neungdongro 120, Gwangjin-gu, Seoul, 05029 Korea
| | - Tae-Hwa Han
- Health IT Center, College of Medicine, Yonsei University, Seoul, Korea
| | - Hyunjung Lee
- Department of Nursing, College of Nursing, Konyang University, Daejeon, Korea
| |
Collapse
|
|
41
|
Abstract
Excess adiposity is a risk factor for several cancer types. This is likely due to complex mechanisms including alterations in the lipid milieu that plays a pivotal role in multiple aspects of carcinogenesis. Here we consider the direct role of lipids in regulating well-known hallmarks of cancer. Furthermore, we suggest that obesity-associated remodelling of membranes and organelles drives cancer cell proliferation and invasion. Identification of cancer-related lipid-mediated mechanisms amongst the broad metabolic disturbances due to excess adiposity is central to the identification of novel and more efficacious prevention and intervention strategies.
Collapse
Affiliation(s)
- J Molendijk
- QIMR Berghofer Medical Research Institute, Herston, Brisbane, 4006, Australia.
| | | | | | | |
Collapse
|
|
42
|
Donohoe F, Wilkinson M, Baxter E, Brennan DJ. Mitogen-Activated Protein Kinase (MAPK) and Obesity-Related Cancer. Int J Mol Sci 2020; 21:ijms21041241. [PMID: 32069845 PMCID: PMC7072904 DOI: 10.3390/ijms21041241] [Citation(s) in RCA: 44] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2019] [Revised: 02/06/2020] [Accepted: 02/12/2020] [Indexed: 12/13/2022] Open
Abstract
Obesity is a major public health concern worldwide. The increased risk of certain types of cancer is now an established deleterious consequence of obesity, although the molecular mechanisms of this are not completely understood. In this review, we aim to explore the links between MAPK signalling and obesity-related cancer. We focus mostly on p38 and JNK MAPK, as the role of ERK remains unclear. These links are seen through the implication of MAPK in obesity-related immune paralysis as well as through effects on the endoplasmic reticulum stress response and activation of aromatase. By way of example, we highlight areas of interest and possibilities for future research in endometrioid endometrial cancer and hepatocellular carcinoma associated with non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and MAPK.
Collapse
Affiliation(s)
- Fionán Donohoe
- Ireland East Hospital Gynaeoncology Group, UCD School of Medicine, Mater Misericordiae University, D07R2WY Dublin 7, Ireland; (F.D.); (M.W.)
| | - Michael Wilkinson
- Ireland East Hospital Gynaeoncology Group, UCD School of Medicine, Mater Misericordiae University, D07R2WY Dublin 7, Ireland; (F.D.); (M.W.)
| | - Eva Baxter
- Queensland Centre for Gynaecological Cancer Research, The University of Queensland, Brisbane QLD 4029, Australia;
| | - Donal J. Brennan
- Ireland East Hospital Gynaeoncology Group, UCD School of Medicine, Mater Misericordiae University, D07R2WY Dublin 7, Ireland; (F.D.); (M.W.)
- Systems Biology Ireland, UCD School of Medicine, Belfield, D04V1W8 Dublin 4, Ireland
- Correspondence: ; Tel.: +353-1-7164567
| |
Collapse
|
|
43
|
Xie C, Wen P, Su J, Li Q, Ren Y, Liu Y, Shen R, Ren J. Elevated serum triglyceride and low-density lipoprotein cholesterol promotes the formation of colorectal polyps. BMC Gastroenterol 2019; 19:195. [PMID: 31752704 PMCID: PMC6873463 DOI: 10.1186/s12876-019-1115-9] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2018] [Accepted: 11/13/2019] [Indexed: 01/08/2023] Open
Abstract
BACKGROUND Hyperlipidaemia may be a potential risk factor for the occurrence of intestinal polyps. This study aimed to evaluate correlation between lipidaemia and the formation of colorectal polyps. METHODS One hundred and fourteen patients with colorectal polyps and forty-eight healthy controls were included in this study. Colonoscopies were performed for all patients and controls within 1 week before blood samples were taken. The concentrations of serum lipids and lipoproteins were measured simultaneously using an automatic biochemical analyser. The colorectal lesions were classified based on pathological characteristics, and four types were identified in the study: hyperplastic polyp (HP), tubular adenoma (TA), tubulovillous adenoma (TVA) and adenoma with high-grade dysplasia (A-HGD). Advanced adenoma was classified according to the number, size and histological type of polyps. RESULTS The value of low-density lipoprotein cholesterol (LDL-C) was significantly higher in the group with advanced adenoma than in the controls (p < 0.05). Moreover, the LDL-C values in the HP and TA groups were higher when compared to that of controls (p < 0.05). Obesity, age, and increased TG and LDL-C were independent risk factors for the formation of colorectal polyps. The cut-off values of triglyceride (TG) and LDL-C to distinguish polyp patients from healthy controls were 0.96 mmol/L (AUC = 0.604, p = 0.036) and 3.05 mmol/L (AUC = 0.654, p = 0.002). The combined use of increased LDL-C and TG levels to distinguish polyp patients was effective, with a sensitivity of 50.0% and a specificity of 89.6% (AUC = 0.733, p < 0.01). CONCLUSIONS Colorectal polyps are more often found in obese and older patients. Increased LDL-C and TG were correlated with the occurrence of polyps. Combination of the two serum indicators was useful to assess risk of colorectal lesions, maybe more effective in screening hyperplastic polyp, tubular adenoma and advanced adenoma.
Collapse
Affiliation(s)
- Chenxi Xie
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| | - Pingwu Wen
- Department of Gastroenterology, Meizhou Affiliated Hospital of Sun Yat-sen University, Meizhou, Guangdong Province 514000 People’s Republic of China
| | - Jingling Su
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| | - Qin Li
- Guangzhou Center for Disease Control and Prevention, Guangzhou, Guangdong Province 510080 People’s Republic of China
| | - Yandan Ren
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| | - Yueyu Liu
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| | - Renze Shen
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
- Renze Shen, Department of Stomatology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| | - Jianlin Ren
- Department of Gastroenterology, Zhongshan Hospital Affiliated to Xiamen University, Xiamen, Fujian Province 361000 People’s Republic of China
| |
Collapse
|
|
44
|
Li X, Chen H, Wang G, Feng X, Lyu Z, Wei L, Wen Y, Chen S, Wu S, Hang D, Dai M, Li N, He J. Metabolic Syndrome Components and the Risk of Colorectal Cancer: A Population-Based Prospective Study in Chinese Men. Front Oncol 2019; 9:1047. [PMID: 31681585 PMCID: PMC6811600 DOI: 10.3389/fonc.2019.01047] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 09/26/2019] [Indexed: 12/18/2022] Open
Abstract
Background: To investigate the association between metabolic syndrome (MetS) and the risk of colorectal cancer (CRC) in Chinese men, this study was performed based on data from a large prospective cohort study conducted in China named the Kailuan men cohort study. Methods : A total of 104,333 eligible men who participated in biennial examinations at least once from 2006 to 2015 were recruited. Cox proportional hazards regression models were used to estimate the effects of MetS components on CRC risk. Results: During an 824,211.96 person-years follow-up, 394 CRC cases were verified. Participants with high waist circumference (≥90 vs. <90 cm) had a significantly higher risk of developing incident CRC (HR = 1.32, 95% CI: 1.07–1.64). Compared with participants with no MetS components, the HRs (95% CI) of developing CRC for men with 1, 2, and ≥3 MetS components were 1.53 (1.01–2.32), 1.42 (0.94–2.14), and 1.70 (1.12–2.56), respectively. In addition, a statistically significant trend (P for trend =0.04) of increased CRC risk with an increasing number of abnormal MetS components was observed. Furthermore, compared with no MetS components, the combination of high waist circumference and elevated fasting blood glucose along with normal levels of the other 3 components, showed a 126% increased risk of CRC. Conclusions: Our study suggests that CRC risk is correlated with the number of abnormal MetS components in Chinese men. Men with high waist circumference and elevated fasting blood glucose may have a higher CRC risk even if they do not meet the MetS diagnostic criteria.
Collapse
Affiliation(s)
- Xin Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongda Chen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Gang Wang
- Department of Oncology, Kailuan General Hospital, Tangshan, China
| | - Xiaoshuang Feng
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Zhangyan Lyu
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Luopei Wei
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yan Wen
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Shuohua Chen
- Health Department of Kailuan (Group), Tangshan, China
| | - Shouling Wu
- Health Department of Kailuan (Group), Tangshan, China
| | - Dong Hang
- Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Min Dai
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ni Li
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jie He
- Office of Cancer Screening, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Department of Thoracic Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
45
|
Milano A, Bianco MA, Buri L, Cipolletta L, Grossi E, Rotondano G, Tessari F, Efthymakis K, Neri M. Metabolic syndrome is a risk factor for colorectal adenoma and cancer: a study in a White population using the harmonized criteria. Therap Adv Gastroenterol 2019; 12:1756284819867839. [PMID: 31523276 PMCID: PMC6727097 DOI: 10.1177/1756284819867839] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Accepted: 07/12/2019] [Indexed: 02/05/2023] Open
Abstract
BACKGROUND Metabolic syndrome (MetS) has been associated with colorectal adenomas and cancer. However, MetS definitions have changed over time, leading to a heterogeneity of patients included in previous studies and a substantial inextensibility of observations across time or eastern and western populations. Our aim was to evaluate the association of 'harmonized' criteria-defined MetS and its individual components with colorectal neoplasia and cancer in a western population. METHODS In this multicenter, cross-sectional study, we prospectively evaluated consecutive outpatients who underwent open-access colonoscopy over a 3-month period. MetS was diagnosed according to the 2009 'harmonized' criteria. RESULTS Out of 5707 patients enrolled, we found 213 cancers (3.7%), 1614 polyps (28.3%), 240 nonpolypoid lesions (4.2%), 95 laterally spreading tumors (1.6%). Polyps presented histological low-grade dysplasia in 72.9% of samples, while in 9.8%, high-grade dysplasia or in situ carcinoma was present; dysplasia rates for nonpolypoid lesions were 66.2% (low-grade) and 2.9% (high-grade/in situ carcinoma), while for laterally spreading tumors, 29.6% and 37%, respectively. Overall, MetS prevalence was 41.6%. MetS correlated with both adenomas [odds ratio (OR): 1.76, 95% confidence interval (CI) 1.54-2.00] and cancer (OR: 1.92, 95% CI 1.42-2.58). MetS was the only risk factor for such colonic lesions in subjects younger than 50 years. For all colonic neoplasia, we found MetS and not its individual components to be significantly associated. CONCLUSIONS MetS is risk factor for cancer and adenoma in Whites, especially when younger than 50 years. MetS patients might be considered as a high-risk population also in colorectal cancer screening programs.
Collapse
Affiliation(s)
- Angelo Milano
- Department of Medicine and Aging Sciences and Center of Aging Sciences and Translational Medicine (CeSI-MeT), ‘G.D.’ Annunzio University and Foundation, Chieti, Italy
- Digestive Endoscopy and Gastroenterology Unit, ‘SS Annunziata’ University Hospital, Chieti, Italy
| | - Maria Antonia Bianco
- Division of Gastroenterology and Digestive Endoscopy Unit, Hospital ‘A Maresca’, Torre del Greco, Italy
| | - Luigi Buri
- Gastroenterology and Digestive Endoscopy Unit, Cattinara Hospital, Trieste, Italy
| | - Livio Cipolletta
- Division of Gastroenterology and Digestive Endoscopy Unit, Hospital ‘A Maresca’, Torre del Greco, Italy
| | | | - Gianluca Rotondano
- Division of Gastroenterology and Digestive Endoscopy Unit, Hospital ‘A Maresca’, Torre del Greco, Italy
| | | | - Konstantinos Efthymakis
- Department of Medicine and Aging Sciences and Center of Aging Sciences and Translational Medicine (CeSI-MeT), ‘G.D.’ Annunzio University and Foundation, Chieti, Italy
- Digestive Endoscopy and Gastroenterology Unit, ‘SS Annunziata’ University Hospital, Chieti, Italy
| | - Matteo Neri
- Department of Medicine and Aging Sciences and Center of Aging Sciences and Translational Medicine (CeSI-MeT), ‘G.D.’ Annunzio University and Foundation, Chieti, Italy
- Digestive Endoscopy and Gastroenterology Unit, ‘SS Annunziata’ University Hospital, Chieti, Italy
| |
Collapse
|
|
46
|
Xu H, Tan P, Zheng X, Ai J, Lin T, Jin X, Gong L, Lei H, Yang L, Wei Q. Metabolic syndrome and upper tract urothelial carcinoma: A retrospective analysis from a large Chinese cohort. Urol Oncol 2019; 37:291.e19-291.e28. [DOI: 10.1016/j.urolonc.2018.12.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 11/28/2018] [Accepted: 12/05/2018] [Indexed: 10/27/2022]
|
|
47
|
Ku MS, Fann JCY, Chiu SYH, Chen HH, Hsu CY. Elucidating bidirectional relationship between metabolic syndrome and elevated faecal haemoglobin concentration: a Taiwanese community-based cohort study. BMJ Open 2019; 9:e021153. [PMID: 30826754 PMCID: PMC6429718 DOI: 10.1136/bmjopen-2017-021153] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
Abstract
OBJECTIVES To elucidate the bidirectional temporal relationship between elevated faecal haemoglobin (f-Hb) concentration and metabolic syndrome (MetS). DESIGN A longitudinal cohort study was conducted by utilising data on community-based periodical screening for colorectal cancer with faecal immunochemical test (FIT) and health check-up for MetS. SETTING Population-based organised integrated service screening in Keelung city, Taiwan. PARTICIPANTS We enrolled a total of 62,293 community residents aged 40-79 years. MAIN OUTCOMES AND MEASURES Bidirectional outcomes of FIT-positive and MetS were measured. RESULTS The presence of MetS at baseline led to a statistically significant 31% elevated risk of being incident FIT-positive (adjusted HR, (aHR)=1.31, 95% CI: 1.14 to 1.51) whereas the effect of those with FIT-positive at baseline on incident MetS was not statistically significant (aHR=1.06, 95% CI: 0.89 to 1.25) after adjusting for relevant confounders. Such an effect was particularly noted for three individual components (abnormal waist circumference, higher fasting plasma glucose and lower high-density lipoprotein). CONCLUSIONS Our finding on the presence of MetS before FIT-positive based on bidirectional relationship assessment suggests the control of MetS may contribute to reducing the risk of colorectal neoplasia through the early surveillance of f-Hb. However, such a temporal epidemiological finding still needs to be verified by using other external data.
Collapse
Affiliation(s)
- Mei-Sheng Ku
- Graduate Institute of Environmental Health, College of PublicHealth, National Taiwan University, Taipei, Taiwan
| | - Jean Ching-Yuan Fann
- Department of Health Industry Management, School of Healthcare Management, Kainan University, Taoyuan, Taiwan
| | - Sherry Yueh-Hsia Chiu
- Department of Health Care Management, Chang Gung University, Taoyuan, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital Kaohsiung Branch, Kaohsiung, Taiwan
| | - Hsiu-Hsi Chen
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
- Innovation and Policy Center for Population Health and Sustainable Environment, College of Public Health, National Taiwan University, Taipei, Taiwan
| | - Chen-Yang Hsu
- Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan
| |
Collapse
|
|
48
|
Myte R, Gylling B, Häggström J, Häggström C, Zingmark C, Löfgren Burström A, Palmqvist R, Van Guelpen B. Metabolic factors and the risk of colorectal cancer by KRAS and BRAF mutation status. Int J Cancer 2019; 145:327-337. [PMID: 30613980 DOI: 10.1002/ijc.32104] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2018] [Revised: 11/29/2018] [Accepted: 12/18/2018] [Indexed: 02/06/2023]
Abstract
Factors related to energy metabolism and the metabolic syndrome, such as higher body mass index (BMI), blood glucose, or blood lipids, and blood pressure, are associated with an increased risk of colorectal cancer (CRC). However, CRC is a heterogeneous disease, developing through distinct pathways with differences in molecular characteristics and prognosis, and possibly also in risk factors. For subtypes defined by KRAS and BRAF mutation status, BMI is the only metabolic factor previously studied, with inconsistent findings. We investigated whether associations between BMI, blood glucose, blood lipids, and blood pressure and CRC risk differed by tumor KRAS and BRAF mutation status in 117,687 participants from two population-based cohorts within the Northern Sweden Health and Disease Study (NSHDS). Hazard ratios (HRs) for overall CRC and CRC subtypes by metabolic factors were estimated with Cox proportional hazards regression, using multiple imputation to handle missing exposure and tumor data. During a median follow-up of 15.6 years, we acquired 1,250 prospective CRC cases, of which 766 cases had complete baseline and molecular tumor data. Consistent with previous evidence, higher BMI, total cholesterol, triglyceride levels, and blood pressure were associated with an increased risk of overall CRC (HRs per 1 standard deviation increase: 1.07 to 1.12). These associations were similar regardless of CRC subtype by KRAS and BRAF mutation status (all pheterogeneity > 0.05). The same was true for subtypes based on microsatellite instability status. Poor metabolic health may therefore be a universal mechanism for colorectal cancer, acting across multiple developmental pathways.
Collapse
Affiliation(s)
- Robin Myte
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden
| | - Björn Gylling
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Jenny Häggström
- Department of Statistics, Umeå School of Business and Economics, Umeå University, Umeå, Sweden
| | - Christel Häggström
- Department of Biobank Research, Umeå University, Umeå, Sweden.,Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Carl Zingmark
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | | | - Richard Palmqvist
- Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden
| | - Bethany Van Guelpen
- Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.,Wallenberg Centre for Molecular Medicine, Umeå University, Umeå, Sweden
| |
Collapse
|
|
49
|
Malcomson FC. Mechanisms underlying the effects of nutrition, adiposity and physical activity on colorectal cancer risk. NUTR BULL 2018. [DOI: 10.1111/nbu.12359] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
|
|
50
|
Mantovani A, Dauriz M, Byrne CD, Lonardo A, Zoppini G, Bonora E, Targher G. Association between nonalcoholic fatty liver disease and colorectal tumours in asymptomatic adults undergoing screening colonoscopy: a systematic review and meta-analysis. Metabolism 2018; 87:1-12. [PMID: 29935236 DOI: 10.1016/j.metabol.2018.06.004] [Citation(s) in RCA: 87] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2018] [Revised: 06/13/2018] [Accepted: 06/18/2018] [Indexed: 12/14/2022]
Abstract
BACKGROUND It is currently uncertain whether non-alcoholic fatty liver disease (NAFLD) is associated with an increased risk of colorectal tumours. We performed a meta-analysis of relevant observational studies to quantify the magnitude of the association between NAFLD and risk of colorectal adenomas and cancer. METHODS We searched PubMed, Scopus and Web of Science from January 2000 to November 2017 using pre-defined keywords to identify observational studies of asymptomatic adults undergoing screening colonoscopy, in which NAFLD was diagnosed by imaging or histology. Data from selected studies were extracted and meta-analysis was performed using random-effects modelling. RESULTS Eleven observational studies (8 cross-sectional and 3 longitudinal) with aggregate data on 91,124 asymptomatic adults (32.1% with NAFLD) of predominantly Asian descent accounting for a total of 14,911 colorectal adenomas and 1684 cancers were included in the final analysis. NAFLD was associated with an increased risk of prevalent colorectal adenomas (n = 7 studies using liver imaging techniques; random-effects odds ratio [OR] 1.28, 95% CI 1.11-1.48; I2 = 82.9% or n = 1 study using liver biopsy; random-effects OR 1.61, 95% CI 0.90-2.89) and cancer (n = 4 studies using liver imaging techniques; random-effects OR 1.56, 95% CI 1.25-1.94; I2 = 65.6% or n = 1 study using liver biopsy; random-effects OR 3.04, 95% CI 1.29-7.18). NAFLD was also associated with an increased risk of incident colorectal adenomas (n = 3 studies; random-effects hazard ratio [HR] 1.42, 95% CI 1.18-1.72; I2 = 0%) and cancer (n = 1 study; random-effects HR 3.08, 95% CI 1.02-9.03). These risks were independent of age, sex, smoking, body mass index and diabetes (or metabolic syndrome). Sensitivity analyses did not alter these findings. Funnel plot and Egger's test did not reveal significant publication bias. CONCLUSIONS This meta-analysis of observational studies (involving asymptomatic individuals of predominantly Asian descent undergoing screening colonoscopy) suggests that NAFLD (detected by imaging or biopsy) is independently associated with a moderately increased prevalence and incidence of colorectal adenomas and cancer. However, the observational design of the studies does not allow for proving causality, and the possibility of residual confounding by some unmeasured factors cannot be ruled out. More prospective studies, particularly in European and American individuals, and mechanistic studies are required to better understand the association between NAFLD and colonic carcinogenesis.
Collapse
Affiliation(s)
- Alessandro Mantovani
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Marco Dauriz
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Christopher D Byrne
- Nutrition and Metabolism, Faculty of Medicine, University of Southampton, UK; Southampton National Institute for Health Research Biomedical Research Centre, University Hospital Southampton, Southampton General Hospital, Tremona Road, Southampton, UK
| | - Amedeo Lonardo
- Department of Internal Medicine and Metabolic Diseases, Nuovo Ospedale Sant'Agostino Estense di Baggiovara, Modena, Italy
| | - Giacomo Zoppini
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Enzo Bonora
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy
| | - Giovanni Targher
- Section of Endocrinology, Diabetes and Metabolism, Department of Medicine, University and Azienda Ospedaliera Universitaria Integrata of Verona, Verona, Italy.
| |
Collapse
|