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?

  • Karimi, Khatoon (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Mahmoudi, Touraj (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Karimi, Negar (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Dolatmoradi, Hesamodin (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Arkani, Maral (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Farahani, Hamid (Department of Physiology, School of Medicine, Qom University of Medical Sciences) ;
  • Vahedi, Mohsen (Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences) ;
  • Parsimehr, Elham (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences) ;
  • Dabiri, Reza (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Nobakht, Hossein (Internal Medicine Department, Semnan University of Medical Sciences) ;
  • Asadi, Asadollah (Department of Biology, Faculty of Science, University of Mohaghegh Ardabili) ;
  • Zali, Mohammad Reza (Gastroenterology and Liver Diseases Research Center, Shahid Beheshti University of Medical Sciences)
  • Published : 2013.09.30


Background: Several epidemiological studies have shown associations between colorectal cancer (CRC) risk and 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 CRC susceptibility. In this study, we hypothesized that polymorphisms in the genes involving the insulin pathway are associated 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 risk of CRC were evaluated using a case-control design with 167 CRC cases and 277 controls by the PCR-RFLP method. Results: Overall, we observed no significant difference in genotype and allele frequencies between the cases and controls for the IGF-I, IGFBP-3, INSR, IRS2 gene variants and CRC before or after adjusting for confounders (age, BMI, sex, and smoking status). However, we observed that the IRS2 (rs2289046) GG genotype compared 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 polymorphic variations in IGF-I, IGFBP-3, INSR, IRS2 genes and risk of CRC. However, the evidence for a link between the IRS2 (rs2289046) variant and risk of CRC dependent on the BMI of the subjects, requires confirmation in subsequent studies with greater sample size.


Colorectal cancer;insulin pathway genes;polymorphism;PCR-RFLP


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