%0 Journal Article
%A Bouras, Emmanouil
%A Gill, Dipender
%A Zuber, Verena
%A Murphy, Neil
%A Dimou, Niki
%A Aleksandrova, Krasimira
%A Lewis, Sarah J
%A Martin, Richard M
%A Yarmolinsky, James
%A Albanes, Demetrius
%A Brenner, Hermann
%A Castellví-Bel, Sergi
%A Chan, Andrew T
%A Cheng, Iona
%A Gruber, Stephen
%A Van Guelpen, Bethany
%A Li, Christopher I
%A Le Marchand, Loic
%A Newcomb, Polly A
%A Ogino, Shuji
%A Pellatt, Andrew
%A Schmit, Stephanie L
%A Wolk, Alicja
%A Wu, Anna H
%A Peters, Ulrike
%A Gunter, Marc J
%A Tsilidis, Konstantinos K
%T Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis.
%J International journal of epidemiology
%V 53
%N 3
%@ 0300-5771
%C Oxford
%I Oxford Univ. Press
%M DKFZ-2024-00992
%P dyae067
%D 2024
%X Colorectal cancer (CRC) is the third-most-common cancer worldwide and its rates are increasing. Elevated body mass index (BMI) is an established risk factor for CRC, although the molecular mechanisms behind this association remain unclear. Using the Mendelian randomization (MR) framework, we aimed to investigate the mediating effects of putative biomarkers and other CRC risk factors in the association between BMI and CRC.We selected as mediators biomarkers of established cancer-related mechanisms and other CRC risk factors for which a plausible association with obesity exists, such as inflammatory biomarkers, glucose homeostasis traits, lipids, adipokines, insulin-like growth factor 1 (IGF1), sex hormones, 25-hydroxy-vitamin D, smoking, physical activity (PA) and alcohol consumption. We used inverse-variance weighted MR in the main univariable analyses and performed sensitivity analyses (weighted-median, MR-Egger, Contamination Mixture). We used multivariable MR for the mediation analyses.Genetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95
%K Humans
%K Colorectal Neoplasms: genetics
%K Colorectal Neoplasms: epidemiology
%K Mendelian Randomization Analysis
%K Body Mass Index
%K Risk Factors
%K Obesity: genetics
%K Obesity: epidemiology
%K Insulin-Like Growth Factor I: metabolism
%K Alcohol Drinking: epidemiology
%K BMI (Other)
%K Body mass index (Other)
%K CRC (Other)
%K Mendelian randomization (Other)
%K colorectal cancer (Other)
%K mediation analysis (Other)
%K obesity (Other)
%K Insulin-Like Growth Factor I (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:38725300
%R 10.1093/ije/dyae067
%U https://inrepo02.dkfz.de/record/290093