Effects of selected genetic polymorphisms in xeroderma pigmentosum complementary group D on gastric cancer

DNA repair capacity (DRC) can be altered based on sequence variations in DNA repair genes, which may result in cancer susceptibility. The current study was to evaluate the association between genetic polymorphisms, including associated haplotypes of xeroderma pigmentosum complementary group D (XPD), and individual susceptibility to gastric cancer. Two-hundred-eight patients with gastric cancer and 339 healthy controls were enrolled in this study. Their genomic DNA was extracted from peripheral blood leukocytes. The genotypes at exon 6, 10 and 23 were identified by polymerase chain reaction (PCR). Unconditional logistic regression model was used to analyze the effects of the polymorphisms, including the corresponding haplotypes, on the susceptibility to develop gastric cancer. The proportion of genotypes GA or AA at exon 10 in cases was showed to be significantly higher than that in controls (P < 0.01, P < 0.01, respectively). The risk of genotype GA or AA carriers to develop gastric cancer was simultaneously much higher (OR = 3.38, 95% CI 2.30-4.95; OR = 6.13, 95% CI 2.45-15.31, respectively). The allele A at exon 10 was also observed to manifest a substantially higher frequency in cases compared to controls (P < 0.01), which might indicate an increased tendency to gastric cancer (OR = 2.40, 95% CI 1.81-3.17). No significant differences were found in the distribution of genotypes at exon 6 or 23 between the two groups (P = 0.23, P = 0.52; P = 0.44, P = 0.56, respectively). By haplotype analysis, haplotype AAA could individually increase incidence of gastric cancer (P < 0.01, OR = 3.39, 95% CI 2.21-5.21). In contrast, haplotypes CGA and AGA were showed a decline in gastric cancer susceptibility (OR = 0.67, 95% CI 0.46-0.97; OR = 0.58, 95% CI 0.41-0.83, respectively). The rest of haplotypes made no statistically significant difference between cases and controls. Taken together, this study demonstrates that the genetic variation at exon 10 and haplotype AAA may be contributing factors in developing gastric cancer.