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654PASSOCIATION OF POLYMORPHISMS WITH GASTRIC CANCER: SINGLE NUCLEOTIDE POLYMORPHISMS IN PROMOTER OR MICRO RNA BINDING SITE?

ABSTRACT Aim: Gastric cancer(GC) is a leading cause of cancer related death in the world. Chronic inflammation is one of the initial phases in development of gastric cancer which occurs as a result of cytokine secretion,like TNF-a . One of the most important agents in the pathogenesis of cancer is tumor necrosis factor (TNF).Single nucleotide polymorphisms (SNPs) have a principle role in gene expression of TNF-a which may leads to Gastric cancer. Moreover, another important regulatory gene expression is micro RNA(mirRNA). The binding of micro RNAs to messenger RNAs can be affected by SNPs that can increase the risk of cancers. SNPs in mirRNAs could cause some changes on cancer-related genes, such as RAF-1. Considering the importance of rs1799964 in TNF-a gene and rs1051208 of RAF1 gene, the aim of our study was to find the relationships between mentioned SNPs and Gastric cancer in an Iranian population. Methods: In this study we investigated the relationship of the rs1799964 in TNF-a gene which is located on the promoter and the RAF1 gene rs1051208 located on 3′UTR, with the risk of CRC among 300 Iranian individuals based on a case-control study. Genomic DNA was isolated from 5 µl of blood by a standard salting out method extraction.Genotyping of SNPs was performed by PCR-RFLP method and for approving the outcomes 10% of genotyping results with RFLP, were sequenced. Results: The comparison between case and control group revealed a significant association between TNF-a gene rs1799964 and risk of Gastric cancer. The TT genotype showed increased risk for Gastric cancer with odds ratio 1.53, P = 0.01. Moreover, rs1799964 of TNF-a gene T allele indicates statistically significant association with GC risk OR 1.47, P = 0.02. We did not observe any remarkable association between rs1051208 of RAF1 gene and risk of gastric cancer. Conclusions: The results indicated that rs1799964 TT genotype in TNF-a gene and also the T allele in mentioned SNP may act as a risk factor in susceptibility to Gastric cancer. Since SNPs are among noticeable biomarkers for predicting susceptibility to dreadful diseases specially cancers, and also by developments in detecting such SNPs, there is an expectation of getting near to personalized medicine which every individual could have a specific diagnosis and also treatment based on his/her genome characteristics. Disclosure: All authors have declared no conflicts of interest.