核苷酸切除修复基因和谷胱甘肽-S-转移酶基因多态与胆道癌风险关系的研究

Relationship between polymorphisms of DNA repair genes and glutathione-S-transferase genes and risk of biliary tract cancer

目的:研究核苷酸切除修复基因XPA、XPC、XPD、XPG及Ⅱ相代谢酶基因GSTM1、GSTT1多态与上海市市区人群胆道癌风险的关系。方法:采用全人群病例-对照研究的方法,运用聚合酶链反应-限制性片段长度多态(polymerase chain reaction-restriction fragment length polymorphism,PCR-RFLP)的方法对443例胆道癌患者和845例正常对照进行基因型分析。比较各基因型在病例与对照中分布频率的差异,并探讨其与胆道癌之间的关系。结果:XPD exon10-Asp312Asn和exon23-Lys751Gln多态位点的频率分布在壶腹癌病例和对照之间的差异有统计学意义(P<0.05),调整了年龄、性别、吸烟、胆石症和高血压后,证实Asn/Asn和Gln/Gln基因型可能增加壶腹癌的危险,比值比(odds ratio,OR)分别为32.03和9.33,且趋势检验有统计学意义。未发现其他修复基因多态位点与胆道癌有关联。分层分析显示,GSTM1缺失型可增加女性胆囊癌发生的危险,OR=1.73(95%可信区间:1.06～2.82)。在胆道癌的发生中,GSTM1与部分修复基因存在联合作用。结论:XPD exon10-Asn/Asn基因型和exon23 Gln/Gln基因型可能与壶腹癌的危险性有关。GSTM1缺失型可能增加女性胆囊癌发生的危险,且GSTM1基因型与部分修复基因之间可能存在联合作用。

Objective：To investigate the potential association of polymorphisms of DNA repair gene （XPA, XPD, XPC, XPG） and Ⅱ phase metabolizing enzyme glutathione-S-transferase genes （ GSTM1, GSTT1 ） with the risk of biliary tract cancer in a Chinese population of urban Shanghai. Methods： Population-based case-control study was carried out. The genotypes of a total of 443 patients with biliary tract cancer and 845 cancer-free controls were determined for polymorphisms by polymerase chain reaction-restrictive fragment length polymorphism （PCR-RFLP） method. The odds ratios （OR） and 95% confidence intervals （CI） were calculated using unconditional logistic regression. The difference of alle frequency was compared between patients and normal controls Results ： The frequency of XPD exon10-Asp312Asn and exon23-Lys751 Gln was significantly different between ampullary carcinoma patients and normal controls （P 〈 0. 05 ）. XPD 312Asn/Asn and XPD 751 Gln/Gln genotype carriers had increased risk of ampullary carcinoma after adjustment of age, gender, smoking status, cholelithiasis, and hypertention. The adjusted ORs were 32.03 and 9.33, respectively. The difference was significant by trend test. No relationship was found between polymorphisms of XPA, XPC and XPG and the risk of biliary tract cancer. Stratified analysis showed that women with GSTM1 null genotype had increased risk of gallbladder cancer （ OR = 1. 73,95% CI： 1.06-2.82）. In the tumorigenesis of biliary tract cancer GSTM1 and some DNA repair gene bad synergistic effects. Conclusion：XPD exon10-Asp312Asn and exon23 Gln/Gln genotype might be associated with the risk of ampullary carcinoma. Women with GSTM1 null genotype might have increased risk of gallbladder cancer in urban Shanghai. There might be interactions between selected DNA repair genes and GSTM1 polymorphisms.