Contribution of DNA Repair Xeroderma Pigmentosum Group D Genotype to Gastric Cancer Risk in Taiwan

Aim: It has been proposed that genetic variations of DNA repair genes confer susceptibility to cancer, and the DNA repair gene xeroderma pigmentosum group D (XPD), the caretaker of genome stability, is thought to play a major role in the nucleotide excision repair system. We investigated three genotypes of XPD, at promoter -114 (rs3810366), and codon 312 (rs1799793), 751 (rs13181), and their associated with gastric cancer susceptibility in a Taiwanese population. Materials and Methods: In the present study, 121 patients with gastric cancer and 363 gender- and age-matched healthy controls were recruited and genotyped for XPD by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) methodology, and the association of XPD genotype with gastric cancer risk was investigated. Results: We found a significant difference in the distribution of A allele-bearing XPD codon 312 genotypes [odds ratio (OR) = 1.64, 95% confidence interval (CI) = 1.20-2.25, p = 0.0019], but not in XPD codon 751 or promoter -114 sites, between the gastric cancer and control groups. Those who had G/A or A/A at XPD codon 312 had a 1.83-fold (95% CI = 1.14-2.95, p = 0.0159) and 1.87-fold (95% CI = 1.04-3.34, p = 0.0378) increased risk of gastric cancer compared to those with G/G. The risk for G/A and A/A genotypes had synergistic effects with alcohol drinking (OR = 11.27, 95% CI = 3.7234.17, p = 0.0001), cigarette smoking (OR = 23.20, 95% CI = 6.24-86.23, p = 0.0001) and Helicobacter pylori infection (OR = 5.38, 95% CI = 2.76-10.52, p = 0.0001) on gastric cancer susceptibility. Conclusion: Our findings suggest that the A allele of XPD codon 312 may contribute to gastric carcinogenesis and may be useful for early detection and prevention of gastric cancer.