目的:研究DNA损伤修复基因hOGG1和XPD单核苷酸多态性与胃癌、肝癌和结直肠癌易感性的关系。方法:用DNA抽提试剂盒从肿瘤患者外周血标本中抽提基因组DNA,其中胃癌患者98例,肝癌患者76例,结直肠癌患者95例,非肿瘤对照组80例。采用聚合酶链式反应-限制性片断长度多态性(PCR-RFLP)方法测定hOGG1 Ser326Cys和XPD Lys751Gln的基因型分布,采用SPSS 16.0软件进行分析。结果:携带hOGG1Cys 326Cys基因型使患胃癌、肝癌和结直肠癌的风险分别增加1.485倍(P=0.036)、1.114倍(P=0.011)和1.940倍(P=0.001)。携带hOGG1 326Cys等位基因同时饮酒者,可增加胃癌发病风险38%(P=0.008),肝癌发病风险增加30%(P=0.036);携带XPDLys751Gln基因型胃癌、肝癌和结直肠癌的风险分别增加2.150倍(P=0.003)、2.340倍(P=0.002)和1.292倍(P=0.008)。携带XPD751Gln等位基因并饮酒可使胃癌发病风险增加26%(P=0.027),肝癌发病风险增加40%(P=0.005)。同时携带hOGG1 326Cys和XPD 751Gln等位基因,患胃癌的危险性降低24%(P=0.010),患肝癌和结直肠癌的危险性分别增加40%(P=0.003)和23%(P=0.016)。结论:hOGG1基因的Cys 326Cys基因型和XPD基因的Lys751Gln基因型可能是胃癌、肝癌和结直肠癌发生的遗传易感因素,携带hOGG1326Cys等位基因或XPD 751Gln等位基因且饮酒,可能增加胃癌和肝癌的易感性。
Objective: To investigate the interaction among human 8 - oxoguanine DNA glycosylase 1 ( hOGG1 ), xeroderma pigmentosum group D ( XPD ) gene polymorphism, and genetic susceptibility of gastric cancer, liver cancer, and colorectal cancer. Methods: Peripheral blood samples were obtained from patients with gastric cancer ( n = 98 ), liver cancer ( n = 76 ), colorectal cancer ( n = 95 ), and healthy controls ( n = 80 ). DNA extraction kits were used for genomic DNA preparation. Genotyping was confirmed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). SPSS 16.0 was used for data processing. Results: The hOGG1 Cys326Cys genotype had an increased risk of gastric cancer ( adjusted OR = 1.485, 95 % CI = 0.722 - 3.052 ), liver cancer ( adjusted OR = 1.114, 95 % CI = 0.497 - 2.495 ), and colorectal cancer ( adjusted OR = 1.940, 95 % CI = 0.879 - 4.280 ). Among alcohol drinkers, the hOGG1 326Cys allele carriers increase the risk of gastric cancer ( 38 %, P = 0.008 ) and liver cancer ( 30 %, P = 0.036 ). The XPDLys751Gln genotype had an increased risk of gastric cancer ( adjusted OR = 2.150, 1.059 - 4.365 ), liver cancer ( adjusted OR = 2.340, 0.755 - 7.253 ), and colorectal cancer ( adjusted OR = 1.292, 1.028 - 2.542 ). Among alcohol drinkers, the XPD751Gln allele carriers increase the risk of gastric cancer ( 26 %, P = 0.027) and liver cancer ( 40 %, P = 0.005 ). Carriers of either hOGG1 326Cys or XPD 751Gln have a decreased risk of gastric cancer ( 24 %, P = 0.010 ) and increased risk of liver cancer ( 40 %, P = 0.003 ) and colorectal cancer ( 23 %, P = 0.016 ). Conclusion: The hOGG1 Cys326Cys and XPD Lys751Gln genotypes may be correlated with susceptibility to gastric cancer, liver cancer, and colorectal cancer. The hOGG1 326Cys and XPD751Gln alleles may contribute to the etiology of gastric cancer and liver cancer among alcohol drinkers in the Chinese population.