DNA修复基因XPD单核苷酸多态与胆道癌遗传易感性

目的:研究核苷酸切除修复基因XPDAsp312Asn位点以及Lys751Gln位点多态与上海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PCR-RFLP对443名胆道癌患者和448名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,并探讨基因、环境因素在胆道癌发生过程中的作用。结果:与携带XPD 751Lys/Lys基因型者比较,携带Gln/Gln基因型者罹患胆道癌的风险显著增加(校正OR=6.32;95%CI=1.16~34.53)。按解剖部位分析显示,风险增高只限于壶腹部癌(校正的OR=13.17;95%CI=1.71~101.38)。携带312Asn/Asn基因型者罹患壶腹部癌的风险显著高于携带Asp/Asp基因型者(校正后OR=20.09;95%CI=1.13~357.99)。在不伴有胆石症人群中,751Gln/Gln基因型携带者罹患胆道癌风险增加(校正后OR=5.92;95%CI=1.05~33.36),提示在不伴有胆石症人群中,遗传因素可能是发生胆道癌的影响因素。而在饮酒人群中携带751Lys/Gln或Gln/Gln基因型者较携带Lys/Lys基因型者患胆道癌风险增加约3倍。结论:XPD 312Asn等位基因以及751Gln等位基因可能是中国上海地区人群胆道癌尤其是壶腹部癌风险的遗传易感因素。

Single nucleotide polymorphism of DNA repair gene XPD and genetic susceptibility of biliary tract cancers

Objective:To investigate the possible associations of DNA repair gene XPD polymorphisms(codon Asp312Asn and codon Lys751Gln) with the risk of biliary tract cancers in a Chinese population from urban Shanghai.Methods:Population based case-control study was carried out.A total of 443 patients with biliary tract cancers and 448 cancer-free controls were geno-(typed) for the 2 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 to evaluate the impact of these 2 polymorphisms and environmental factors on the risk of biliary tract cancers.Results:The XPD 751Gln/Gln genotype carriers had an increased risk of developing biliary tract cancers(adjusted OR=6.32;95% CI=1.16-34.53),especially of carcinoma of Vater's ampulla(adjusted OR=13.17;95% CI=1.71-101.38) compared with XPD 751 Lys/Lys genotype carriers.The XPD 312Asn/Asn genotype carriers had an increased risk of developing carcinoma of Vater's ampulla compared with the XPD 312Asp/Asp genotype carriers(adjusted OR=20.09;95%CI=1.13-357.99).Stratification analysis revealed that among those patients without cholelithiasis,751Gln/Gln genotype carriers had an increased risk of biliary tract cancer(adjusted OR=(5.92;)95%CI=1.05-33.36) indicating that genetic factor had an impact on the biliary tract cancer in patients without cholelithiasis.Among drinkers 751Lys/Gln or Gln/Gln genotype carriers had a 3-fold higher risk of developing biliary tract cancers than Lys/Lys genotype carriers(adjusted OR=3.05,95% CI=1.05-8.86).Conclusions:Asp312Asn and Lys751Gln polymorphisms in the DNA repair gene XPD might be correlated to the susceptibility of biliary tract cancer,especially of carcinoma of Vater's ampulla,in Shanghai.