Association of XRCC1 gene polymorphisms with the survival and clinicopathological characteristics of gastric cancer.

Polymorphisms of the DNA repair gene X-ray repair cross-complementing protein 1 (XRCC1) Arg194Trp, Arg280His, and Arg399Gln have been shown to alter the DNA repair activity and to be associated with genetic susceptibility to several types of cancer. We indentified genotypes of 944 surgically resected gastric cancer (GC) patients by the SNaPshot method to investigate the association of these polymorphisms with clinical progression and outcomes of GC in a Chinese population. The XRCC1 codon 280 His carriers (Arg/His+His/His) held a significantly lower risk of distant metastasis in the dominant model (Pearson chi-square test P=0.019). A weak association of these cases with reduced risk of lymph node metastasis was also found (Pearson chi-square test P=0.051). Individuals carrying at least one Trp allele of XRCC1 codon 194 had an increased risk of death compared with those with Arg/Arg homozygotes in diffuse-type GC (adjusted hazard ratio=1.34, 95% confidence interval=1.05-1.71). Our findings demonstrated that the genetic variant Arg280His in XRCC1 may contribute to cancer progression and that XRCC1 Arg194Trp variants may act as a favorable prognostic indicator of resected GC, particularly among the diffuse-type GC. Larger studies are needed to verify our results in different populations.