A Study on Association of XRCC3 Gene Polymorphism in Gastric cancer risk

Gastric Cancer (GC) is among the common and fatal cancer in the world. DNA repair plays a critical role in protecting the genome of the cell from insults of cancer-causing agents. Inherited polymorphisms of DNA repair genes may contribute to variations in DNA Repair capacity (DRC) and genetic susceptibility to different c ancers. Mammalian cells are constantly exposed to a wide variety of genotoxic a gents from both endogenous and exogenous sources. In human beings, 70 genes are involve d in the five major DNA repair pathways: direct repair, NER, BER, mismatch repa ir and double-strand break repair. The X-ray repair complementing defective repa ir in Chinese hamster cells 3 (XRCC3) gene is a member of the RAD51 gene fami ly. It encodes an important protein that functions in the homologous rec ombination repair of DNA double-strand break. The Kashmir valley has an eleva ted incidence of GC and its etiology is not understood fully yet, though, we are ethni cally and demographically different from the other states of the country and world. The aim of this study was to determine whether single nucleotide poly morphism (SNP) of XRCC3 gene (Thr241Met) of exon7, can influence the risk of gastric cancer in Kashmiri population. About 80 histopathologically confirmed GC case s and 70 healthy controls, age ,gender, ethnicity matched for known genotypes of XRCC3 exon7 were analyzed. Patients medical history and dietary habits were taken for the study as well. The ge notype for this variant was determined using polymerase chain reaction- restriction fra gment length polymorphisms (PCR-RFLP) in 80 histologically confirmed GC patients and 70 frequency-matched healthy controls in Department of Biochemistr y, Government Medical College srinagar. The XRCC3 genotype and allele frequencies were not significantly different between cases and controls (P= 0.92 for ge notype; P= 0:72 for allele). The XRCC3 241Met allele frequency (6.6%) was signifi cantly lower in healthy Kashmiri controls than previously reported healthy US Caucasian controls (38.9%). Compared with the XRCC3241Thr/Thr genoty pe, the variant XRCC3241Thr/Met and Met/Met genotypes were not associated with an increased risk of gastric cancer (adjusted odds ratio (ORa), 1.19; 95% confiden ce interval (CI), 0.44-3.18). These finding s suggest that polymorphisms of XRCC3 Thr241Met may not play a role in the etiology of GC. Further studies with a larger number of subjects and simultaneous measurement of different pol ymorphisms in DNA repair genes in the same pathway are needed