Waist circumference, a body shape index, and molecular subtypes of colorectal cancer: A pooled analysis of four cohort studies.

Background Waist circumference (WC) and its allometric counterpart, "a body shape index" (ABSI), are risk factors for colorectal cancer (CRC); however, it is uncertain whether associations with these body measurements are limited to specific molecular subtypes of the disease. Methods Data from 2,772 CRC cases and 3,521 controls were pooled from four cohort studies within the Genetics and Epidemiology of Colorectal Cancer Consortium. Four molecular markers (BRAF mutation, KRAS mutation, CpG island methylator phenotype, and microsatellite instability) were analysed individually and in combination (Jass-types). Multivariable logistic and multinomial logistic models were used to assess the associations of WC and ABSI with overall CRC risk and in case-only analyses evaluating heterogeneity by molecular subtype, respectively. Results Higher WC (ORper 5cm=1.06, 95%CI:1.04-1.09) and ABSI (ORper 1-SD=1.07, 95%CI:1.00-1.14) were associated with elevated CRC risk. There was no evidence of heterogeneity between the molecular subtypes. No difference was observed regarding the influence of WC and ABSI on the four major molecular markers in proximal colon, distal colon, and rectal cancer, as well as in early and later onset CRC. Associations did not differ in the Jass-type analysis. Conclusions Higher WC and ABSI were associated with elevated CRC risk; however, they do not differentially influence all four major molecular mutations involved in colorectal carcinogenesis but underscore the importance of maintaining a healthy body weight in CRC prevention. Impact The proposed results have potential utility in colorectal cancer prevention.