Is there an Association between Variants in Candidate Insulin Pathway Genes IGF-I, IGFBP-3, INSR, and IRS2 and Risk of Colorectal Cancer in the Iranian Population?


Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) riskand type 2 diabetes and obesity. Any effects would be expected to be mediated through the insulin pathway.Therefore it is possible that variants of genes encoding components of the insulin pathway play roles in CRCsusceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway areassociated with risk of CRC. Materials and
Methods: The associations of four single nucleotide polymorphisms(SNPs) in IGF-I (rs6214), IGFBP-3 (rs3110697), INSR (rs1052371), and IRS2 (rs2289046) genes with the riskof CRC were evaluated using a case–control design with 167 CRC cases and 277 controls by the PCR–RFLPmethod.
Results: Overall, we observed no significant difference in genotype and allele frequencies between thecases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting forconfounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotypecompared with AA+AG genotypes has a protective effect for CRC in normal weight subjects (p=0.035, OR=0.259,95%CI= 0.074-0.907).
Conclusions: These findings do not support plausible associations between polymorphicvariations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link betweenthe IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation insubsequent studies with greater sample size.