Genetic polymorphisms of XRCC1 and risk of gastric cancer

Coding polymorphisms of the DNA repair gene XRCC1 have been shown to affect the DNA repair capacity and to be associated with genetic susceptibility to carcinogenesis. In our association study between three amino acid substitution polymorphisms of XRCC1 (Arg194Trp, Arg280His, and Arg399Gln) and the risk of gastric cancer in the Korean population, none of the polymorphisms were associated with increased risk of gastric cancer. We then extended our study by building haplotypes of the entire XRCC1 gene with six single neuclotide polymorphisms (SNPs), including two novel polymorphisms at the 5'-flanking sequence. When haplotype frequencies in cases and controls and haplotype-specific odds ratios (ORs) were estimated, haplotype A (194Trp, 280Arg, and 399Arg) was associated with significant reduction in gastric cancer risk (adjusted OR = 0.65, 95% CI = 0.43-0.99) whereas haplotype D (194Arg, 280Arg, and 399Arg alleles) was a risk type for gastric cancer (adjusted OR = 1.57, 95% CI = 0.93-2.65). The association with the haplotype D was more pronounced in the cancers of antrum (adjusted OR = 2.06, 95% CI = 1.03-2.00). Our results suggest that the haplotype estimation is advantageous for association studies of such a complex disease as gastric cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.