Gene polymorphisms related to insulin resistance and gene–environment interaction in colorectal cancer risk

Abstract

Background and aim: Insulin resistance (IR) is an established risk factor for colorectal cancer (CRC) and both IR and CRC physiologically overlap. As such, this study explored the relationship of IR-related gene polymorphisms and CRC risk.Subjects and methods: A total of 400 case-control pairs were profiled in terms of their lifestyle, dietary habits and blood sample. Classification and regression tree (CART) and generalized multi-factor dimensionality reduction (GMDR) were employed to test the gene–environment interactions in CRC risk.Results: ADIPOQ rs2241766 TG + GG, ADIPOQ rs1501299 GT + TT and CAPN-10 rs3792267 GA + AA were significantly related to CRC risk. In CART, individuals with high red meat consumption, CAPN-10 rs3792267 GG, ADIPOQ rs1501299 GG and ADIPOQ rs2241766 TG + GG had an OR of 1.821 (95% CI = 1.124–2.951). The overall best GMDR model including the four factors had the maximal TBA (0.5943) and CVC (10/10) (p = 0.0010). Subjects with high red meat consumption and the three risk genotypes had a CRC risk 10.195-times (95% CI = 2.164–48.030) greater than those with low red meat and null risk genotypes.Conclusions: ADIPOQ rs2241766, ADIPOQ rs1501299 and CAPN-10 rs3792267 are significantly associated with CRC risk and the combination of the three polymorphisms and red meat affect CRC risk.