Polymorphisms of the DNA repair gene XRCC1 and risk of gastric cancer in aChinese population

Gastric cancer remains the leading cause of cancer death in China and other countries in eastern Asia. Studies of gastric cancer have revealed that it is a disease of complex etiology involving dietary, infectious, environmen tal, occupational and genetic factors. DNA repair capacity has been suggest ed as a genetic factor contributing to variation in susceptibility to cance r. In the present study, we described an association between 2 polymorphism s of the DNA repair gene XRCC1 and risk of gastric cancer in a Chinese popu lation. We used a polymerase chain reaction-based assay to detect Pvu II an d Nci I restriction fragment length polymorphisms (XRCC1 26304 C-->T and XR CC1 28152 G-->A, respectively) in 188 patients with gastric cancer and 166 healthy controls. The XRCC1 26304 T allele (194Trp) frequency (34.6%) was h igher and the XRCC1 28152 A allele (399Gln) frequency (25.6%) was lower in healthy Chinese controls than previously reported healthy U.S. Caucasian co ntrols (7.2% and 34.1%, respectively). Multivariate logistic regression ana lysis revealed that the putative high-risk genotypes XRCC1 26304 CC and XRC C1 28152 GA/AA were associated with a non-significant increased risk for ga stric cancer (adjusted odds ratio [OR]= 1.45, 95% confidence interval [CI]= 0.93-2.25 and OR=1.53, 95% CI= 0.98-2.39, respectively) compared with othe r genotypes. However, the XRCC1 26304 CC genotype was associated with a sig nificantly increased risk for gastric cardia cancer (adjusted OR= 1.86, 95% CI= 1.09-3.20). Individuals with both putative high-risk genotypes (CC and GA/AA) had a significantly higher risk (adjusted OR= 1.73, 95% CI=1.12-2.6 9), particularly for gastric cardia cancer (adjusted OR=2.18, 95% CI=1.21-3 .94) than individuals with other genotypes. These findings support the hypo thesis that these 2 XRCC1 variants may contribute to the risk of developing gastric cancer, particularly gastric cardia cancer. (C) 2000 Wiley-Liss, I nc.