GWAS-Identified Common Variants for Obesity Are Not Associated with the Risk of Developing Colorectal Cancer
Menée en Allemagne auprès de 1 792 cas et 1 805 témoins, cette étude en population analyse la relation entre 28 variants génétiques associés à l'obésité, et précédemment identifiés dans des études d'association sur le génome entier, et le risque de cancer colorectal
Background: Observational studies have consistently associated obesity with colorectal cancer (CRC) risk. Because both traits are genetically determined and share some metabolic biomarkers, we hypothesized that obesity-related polymorphisms could also influence the risk of developing CRC. Methods: We conducted a comprehensive population-based case-control study in 1792 German CRC cases and 1805 controls to explore associations between 28 obesogenic variants identified through genome-wide association studies (GWAS) and CRC risk. We also evaluated interactions between polymorphisms and body mass index (BMI), type-2 diabetes (T2D) and gender. Results: No evidence of association between obesogenic variants and CRC risk was observed after correction for multiple testing. There was only a remarkable interaction between the LTArs1041981 polymorphism and gender, which modified the risk of CRC (Pinteraction=0.002; males OR=1.14, 95%CI 1.00-1.30 vs. females OR=0.83, 95%CI 0.71-0.97). Conclusions: Our findings showed that obesogenic variants are not a major pathogenetic risk factor for CRC. Impact: This comprehensive population-based case-control study does not provide evidence of a shared genetic component between obesity and CRC.