An exon variant in insulin receptor gene is associated with susceptibility to colorectal cancer in women.

Given the role of insulin resistance in colorectal cancer (CRC), we explored whether genetic variants in insulin (INS), insulin receptor (INSR), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), insulin-like growth factor 1 (IGF1), and insulin-like growth factor binding protein 3 (IGFBP3) genes were associated with CRC risk. A total of 600 subjects, including 261 cases with CRC and 339 controls, were enrolled in this case-control study. Six polymorphisms in INS (rs689), INSR (rs1799817), IRS1 (rs1801278), IRS2 (rs1805097), IGF1 (rs5742612), and IGFBP3 (rs2854744) genes were genotyped using PCR-RFLP method. No significant difference was observed for INS, INSR, IRS1, IRS2, IGF1, and IGFBP3 genes between the cases and controls. However, the INSR rs1799817 "TT + CT" genotype and "CT" genotype compared with "CC" genotype occurred more frequently in the women with CRC than women controls (P = 0.007; OR = 1.93, 95 %CI = 1.20-3.11 and P = 0.002, OR = 2.15, 95 %CI = 1.31-3.53, respectively), and the difference remained significant after adjustment for confounding factors including age, BMI, smoking status, NSAID use, and family history of CRC (P = 0.018; OR = 1.86, 95 %CI = 1.11-3.10 and P = 0.004, OR = 2.18, 95 %CI = 1.28-3.71, respectively). In conclusion, to our knowledge, this study indicated for the first time that the INSR rs1799817 TT + CT genotype and CT genotype compared with the CC genotype had 1.86-fold and 2.18-fold increased risks for CRC among women, respectively. Furthermore, this finding is in line with previous studies which found significant associations between other variants of the INSR gene and CRC risk. Nevertheless, further studies are required to confirm our findings.

Different frequency of epidermal growth factor rs76189946 polymorphism genotype in an Iranian colorectal cancer.

AIM: This study aimed to determinant association between rs76189946 polymorphism of EGF gene and risk of colorectal cancer in an Iranian population. BACKGROUND: Colorectal cancer (CRC) is the third most prevalent cancer in both genders worldwide. The determination of genetic variation becomes a new way to etiology of colorectal cancer. Epidermal growth factor (EGF) is a mitogen that plays an important role in cell growth and tumourigenesis, this protein acts by binding its receptor, EGFR. PATIENTS AND METHODS: DNA samples taken from totally 125 CRC patients and healthy controls were amplified by polymerase chain reaction (PCR) for the rs76189946 polymorphism. Genotypes were analyzed using restriction fragment length polymorphism (RFLP). Finally to confirm the RFLP procedure, 20 of the PCR products were sequenced using the ABI PRISM 3130xl Genetic Analyzer and chain termination method (Applied Biosystems, Carlsbad, CA). RESULTS: Genotype distribution and allele frequency was similar in CRC patients and controls individuals. We expect observe C and G allele in both groups but only was found C allele. CONCLUSION: In this study for first time we identified genetic distribution of exonic rs76189946 polymorphism in EGF gene both CRC patients and healthy controls. These results suggest there wasn't association between EGF polymorphism rs76189946 and risk of colorectal cancer in an Iranian population.

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) 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.