Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer in Turkish subjects

Insulin receptor substrate (IRS) proteins are cytoplasmic adaptors that transmit the signal from the IR and insulin-like growth factor-1 receptor to effector proteins. Overexpression of IRS proteins has been indicated to be linked to cancer development. In addition to their expression profiles, studies have indicated that polymorphisms of IRS1 and IRS2 are also associated with the susceptibility to numerous cancer types. IRS1 Gly972Arg and IRS2 Gly1057Asp are the common variants of these genes. The present study aimed to determine the association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer development. The study included 100 patients with gastric cancer and 100 controls. Single-nucleotide polymorphisms were detected by real-time PCR using Taqman assays. The results suggested that in individuals with the IRS1 Gly/Arg genotype, the odds of having gastric cancer was increased by 7.891-fold (95% CI: 3.251-19.154, P<0.001) and in individuals with the IRS1 Arg/Arg genotype, it was increased by 22.716-fold (95% CI: 6.311-81.761, P<0.001) compared with those with the IRS1 Gly/Gly genotype. Although the IRS2 Gly1057Asp genotype analysis suggested that subjects with the Asp/Asp genotype had a 2,311-fold increased odds of having gastric cancer compared to those with the Gly/Gly genotype, the result was not statistically significant (95% CI: 0.800-6.678, P=0.122). The combined effects of the IRS1 and IRS2 variants on gastric cancer were also determined. The results suggested that individuals with Gly/Arg+Gly/Asp and Gly/Arg+Asp/Asp genotypes had a higher odds of having gastric cancer compared to individuals of the Gly/Gly+Gly/Gly genotype (P=0.001 and P=0.027, respectively). In conclusion, the present results suggested that the IRS1 Gly972Arg and IRS2 Gly1057Asp variations may be associated with an increased susceptibility to develop gastric cancer. Further studies with larger sample sizes are required to support the present results and to explore the use of these variations as a biomarker for gastric cancer.