ArticleInternational journal of epidemiology2024
Identification of potential mediators of the relationship between body mass index and colorectal cancer: a Mendelian randomization analysis.
Article in International journal of epidemiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Sex- and Ethnic-Specific Associations of Serum Lipids with Risk of 12 Cancers: Findings from 506,381 Adults in Two Large Cohorts.Antioxidants (Basel, Switzerland) · 2025Article
- Evolution of the burden of disease for high BMI-associated colorectal cancer, 1990-2021: Global trends, regional heterogeneity, and population risk stratification.Preventive medicine reports · 2025Article
- Phenome-wide association study identifies multiple traits associated with a polygenic risk score for colorectal cancer.Human genomics · 2025Article
- Hyperglycemia and Obesity as the Key Drivers of Increased Colorectal Cancer Mortality in the North Africa and Middle East Region.Oman medical journal · 2025Article
- Associations of blood lipids and LDL cholesterol lowering drug-targets with colorectal cancer risk: a Mendelian randomisation study.British journal of cancer · 2025Article
- The global burden of colorectal cancer attributable to high body-mass index in 204 countries and territories: findings from 1990 to 2021 and predictions to 2035.Frontiers in nutrition · 2024Article
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Authors and funding
27 authors.
Funding
Abstract
backgroundColorectal 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.
methodsWe 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.
resultsGenetically predicted BMI was positively associated with CRC risk [odds ratio per SD (5 kg/m2) = 1.17, 95% CI: 1.08-1.24, P-value = 1.4 × 10-5] and robustly associated with nearly all potential mediators. Genetically predicted IGF1, fasting insulin, low-density lipoprotein cholesterol, smoking, PA and alcohol were associated with CRC risk. Evidence for attenuation was found for IGF1 [explained 7% (95% CI: 2-13%) of the association], smoking (31%, 4-57%) and PA (7%, 2-11%). There was little evidence for pleiotropy, although smoking was bidirectionally associated with BMI and instruments were weak for PA.
conclusionsThe effect of BMI on CRC risk is possibly partly mediated through plasma IGF1, whereas the attenuation of the BMI-CRC association by smoking and PA may reflect confounding and shared underlying mechanisms rather than mediation.
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