Objective: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC). Given thatCRC and IR physiologically overlap and the calpain-10 gene (CAPN10) is a candidate for IR, we explored theassociation between CAPN10 and CRC risk.
Methods: Blood samples of 400 case-control pairs were genotyped,and the lifestyle and dietary habits of these pairs were recorded and collected. Unconditional logistic regression(LR) was used to assess the effects of CAPN10 SNP43 and SNP19, and environmental factors. Both generalizedmultifactor dimensionality reduction (GMDR) and the classification and regression tree (CART) were used to testgene-environment interactions for CRC risk.
Results: The GA+AA genotype of SNP43 and the Del/Ins+Ins/Insgenotype of SNP19 were marginally related to CRC risk (GA+AA: OR = 1.35, 95% CI = 0.92-1.99; Del/Ins+Ins/Ins: OR = 1.31, 95% CI = 0.84-2.04). Notably, a high-order interaction was consistently identified by GMDRand CART analyses. In GMDR, the four-factor interaction model of SNP43, SNP19, red meat consumption, andsmoked meat consumption was the best model, with a maximum cross-validation consistency of 10/10 and testingbalance accuracy of 0.61 (P < 0.01). In LR, subjects with high red and smoked meat consumption and two riskgenotypes had a 6.17-fold CRC risk (95% CI = 2.44-15.6) relative to that of subjects with low red and smokedmeat consumption and null risk genotypes. In CART, individuals with high smoked and red meat consumption,SNP19 Del/Ins+Ins/Ins, and SNP43 GA+AA had higher CRC risk (OR = 4.56, 95%CI = 1.94-10.75) than thosewith low smoked and red meat consumption.
Conclusions: Though the single loci of CAPN10 SNP43 and SNP19are not enough to significantly increase the CRC susceptibility, the combination of SNP43, SNP19, red meatconsumption, and smoked meat consumption is associated with elevated risk.