Metabolic syndrome and risk of gastrointestinal cancers: an investigation using large-scale molecular data

Background & Aims - Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown. -...

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Main Authors: Rothwell, Joseph A. (Author) , Jenab, Mazda (Author) , Karimi, Mojgan (Author) , Truong, Thérèse (Author) , Mahamat-Saleh, Yahya (Author) , Ferrari, Pietro (Author) , Dashti, S. Ghazaleh (Author) , Kühn, Tilman (Author) , Cross, Amanda J. (Author) , Severi, Gianluca (Author) , Gunter, Marc J. (Author) , Murphy, Neil (Author)
Format: Article (Journal)
Language:English
Published: 2022
In: Clinical gastroenterology and hepatology
Year: 2022, Volume: 20, Issue: 6, Pages: e1338-e1352
ISSN:1542-7714
DOI:10.1016/j.cgh.2021.10.016
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.cgh.2021.10.016
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1542356521011290
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Author Notes:Joseph A. Rothwell, Mazda Jenab, Mojgan Karimi, Thérèse Truong, Yahya Mahamat-Saleh, Pietro Ferrari, S. Ghazaleh Dashti, Tilman Kühn, Amanda J. Cross, Gianluca Severi, Marc J. Gunter, and Neil Murphy

MARC

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520 |a Background & Aims - Gastrointestinal cancer risk is influenced by the presence of metabolic syndrome (MetS). However, previous epidemiologic studies lacked full serological biomarker data for the classification of MetS, and the interaction of MetS with germline cancer risk variants is unknown. - Methods - We investigated the associations between MetS and gastrointestinal cancer risk (overall, colorectal, pancreatic, esophageal adenocarcinoma, esophageal squamous cell carcinoma, stomach cardia, stomach non-cardia, hepatocellular carcinoma, and intrahepatic bile duct cancer) in 366,016 United Kingdom Biobank participants with comprehensive serum biomarker and genotype data. MetS status was determined by 3 different definitions at baseline, and, in 15,152 participants, at a repeat assessment after a median of 4.3 years of follow-up. Multivariable hazard ratios and 95% confidence intervals for cancer outcomes were estimated using Cox proportional hazards models. Analyses stratified by polygenic risk score were conducted for colorectal and pancreatic cancers. - Results - During a median follow-up of 7.1 years, 4238 incident cases of a gastrointestinal cancer occurred. MetS at baseline was associated with higher risk of overall gastrointestinal cancer by any definition (hazard ratio, 1.21; 95% confidence interval, 1.13-1.29, harmonized definition). MetS was associated with increased risks of colorectal cancer, colon cancer, rectal cancer, hepatocellular carcinoma, pancreatic cancer in women, and esophageal adenocarcinoma in men. Associations for colorectal cancer and pancreatic cancer did not differ by polygenic risk score strata (P-heterogeneity 0.70 and 0.69, respectively), and 80% of participants with MetS at baseline retained this status at the repeat assessment. - Conclusions - These findings underscore the importance of maintaining good metabolic health in reducing the burden of gastrointestinal cancers, irrespective of genetic predisposition. 
650 4 |a Cancer Genetic Risk 
650 4 |a Cancer Prevention 
650 4 |a Gastrointestinal Neoplasms 
650 4 |a Molecular Epidemiology 
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