Association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer development

KARATAŞ U, Association of IRS1 Gly972Arg and IRS2 Gly1057Asp Polymorphisms with Gastric Cancer Development, Van Yuzuncu Yil University, Institute of Health Sciences, Department of Medical Biology, M.Sc., Van, 2020. Insulin reseptor substrate (IRS) proteins are cytoplasmic adaptors that transmit the signal from insulin receptor (IR) and insulin like growth factor-1 (IGF1) receptor to effector proteins. IRS1 and IRS2 are widely expressed in human tissues. Overexpression of IRS proteins are correlated with cancer development. In addition to their expression profiles, studies have shown that polymorphisms of IRS1 and IRS2 also have responsible for the susceptibility to many cancer types. IRS1 Gly972Arg and IRS2 Gly1057Asp are the common variants of these genes. In this study, it was aimed to determine the association of IRS1 Gly972Arg and IRS2 Gly1057Asp polymorphisms with gastric cancer development. The study included 100 gastric cancer patients and 100 controls. Genomic DNAs were isolated from peripheral blood samples of individuals. Single nucleotide polymorphisms were detected by real time polymerase chain reactions using Taqman Assays. Statistical analyses showed that individuals with IRS1 Gly/Arg genotype had 7.891 fold (95% CI: 3.251-19.154 p<0.001) and individuals with IRS1 Arg/Arg genotype had 22.716 fold (95% CI: 6.311-81.761 p<0.001) higher risk for gastric cancer compared to IRS1 Gly/Gly genotype. Although, IRS2 Gly1057Asp genotype analysis showed that subjects with Asp/Asp genotype had 2,311 fold risk for gastric cancer compared to Gly/Gly genotype, it was not statistically significant (95% CI: 0.800-6.678 p=0.122). As a conclusion, our result showed that IRS1 Gly972Arg and IRS2 Gly1057Asp variations may be associated with increased gastric cancer development. Further studies with larger sample size are needed to support our findings and to use these variations as a biomarker for gastric cancer development. Keywords: IRS1, IRS2, polymorphism, gastric cancer, SNP