TY - JOUR
T1 - Metabolic Syndrome and Risk of Gastrointestinal Cancers
T2 - An Investigation Using Large-scale Molecular Data
AU - Rothwell, Joseph A.
AU - Jenab, Mazda
AU - Karimi, Mojgan
AU - Truong, Thérèse
AU - Mahamat-Saleh, Yahya
AU - Ferrari, Pietro
AU - Dashti, S. Ghazaleh
AU - Kühn, Tilman
AU - Cross, Amanda J.
AU - Severi, Gianluca
AU - Gunter, Marc J.
AU - Murphy, Neil
N1 - Publisher Copyright:
© 2022
PY - 2022/6/1
Y1 - 2022/6/1
N2 - 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.
AB - 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.
KW - Cancer Genetic Risk
KW - Cancer Prevention
KW - Gastrointestinal Neoplasms
KW - Molecular Epidemiology
UR - http://www.scopus.com/inward/record.url?scp=85120170436&partnerID=8YFLogxK
U2 - 10.1016/j.cgh.2021.10.016
DO - 10.1016/j.cgh.2021.10.016
M3 - Article
C2 - 34687971
AN - SCOPUS:85120170436
SN - 1542-3565
VL - 20
SP - e1338-e1352
JO - Clinical Gastroenterology and Hepatology
JF - Clinical Gastroenterology and Hepatology
IS - 6
ER -