北京地区汉族人群DNA修复基因XPD单核苷酸多态性与肺癌及食管癌风险的研究  

Association of genetic polymorphisms in the DNA repair gene XPD with risk of lung and esophageal cancer in a Chinese population in Beijing

作　　者：邢德印[1] 齐军[2] 谭文[1] 缪小平[1] 梁刚[1] 于春媛[1] 吕文富[1] 周传农[3] 吴旻[3] 林东昕[1] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院病因及癌变研究室,北京100021 [2]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院检验科,北京100021 [3]中国医学科学院中国协和医科大学肿瘤研究所肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《中华医学遗传学杂志》2003年第1期35-38,共4页Chinese Journal of Medical Genetics

基　　金：国家杰出青年科学基金 (3982 51 2 2 ) ;国家自然科学基金重大项目 (39990 570 ) ;北京大学肿瘤中心"985"项目~~

摘　　要：目的　研究核苷酸切除修复基因 XPD单核苷酸多态性与北京地区汉族人群肺癌及食管癌风险的关系。方法　采用以医院患者为基础的病例 -对照研究方法 ,包括正常对照 383人 ,肺癌患者 35 1例 ,食管癌患者 32 5例。以聚合酶链反应 -限制性片段长度多态性方法分析了 XPD基因 Asp312 Asn和L ys75 1Gln多态性 ,比较不同基因型与肺癌及食管癌风险的关系 ,并探讨吸烟与基因多态交互作用对患癌风险的影响。结果　与携带 312 Asp/ Asp基因型者比较 ,携带至少 1个 312 Asn等位基因者 (即 Asp/ Asn和 Asn/ Asn基因型 )罹患肺鳞癌的风险增加 1.8倍 (95 % CI1.10～ 2 .93) ,而与肺腺癌无关 (校正的比值比为 1.0 7,95 % CI0 .5 5～ 2 .0 8)。分层分析显示 ,风险型等位基因 312 Asn和 75 1Gln与吸烟有明显的交互作用。吸烟剂量≥ 2 9包 /年且携带 312 Asn或 75 1Gln者罹患肺鳞癌的风险最高 ,校正的比值比分别为 12 .4 4 (95 % CI 4 .97～ 31.17)和 10 .74 (95 % CI 4 .5 1～ 2 5 .5 7)。 XPD基因 Asp312 Asn和 L ys75 1Gln多态与食管鳞癌风险无关。结论　 XPD基因 Asp312 Asn和 L ys75 1Gln多态是北京地区汉族人群肺鳞癌遗传易感因素 ,而与肺腺癌以及食管鳞癌风险无关 ,可能反映了不同组织学类型肺癌以及肺癌和食管癌之间?Objective: XPD polymorphisms at Asp312Asn and Lys751Gln sites have been shown to modulate DNA repair capacity. The authors therefore assessed the relationship between these XPD polymorphisms and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based, case-control study. Methods: Genotypes were determined by PCR-restriction fragment length polymorphism approaches in 383 healthy controls, 351 patients with lung cancer, and 325 patients with esophageal squamous cell carcinoma (SCC). The adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariate logistic regression. Results: Individuals carrying at least one 312Asn variant allele (Asp/Asn and Asn/Asn genotypes) were at an increased risk for lung SCC as compared with those with the Asp/Asp genotype (OR: 1.80; 95% CI: 1.10-2.93; adjusted for age, sex and smoking), but this increased risk was not observed among patients with adenocarcinoma of the lung (adjusted OR: 1.07; 95% CI: 0. 55-2.08). Furthermore, stratified analysis indicated a multiplicative interaction between tobacco smoking and the variant XPD 312Asn and 751Gln alleles on risk of lung SCC. The ORs of lung SCC for the variant XPD 312Asn and 751Gln alleles with smoking ≥29 pack/year were 12.44 (95% CI: 4.97-31.17) and 10.74 (95% CI: 4.51-25.57), respectively. No significant association between the Asp312Asn or Lys751Gln polymorphism and the risk of esophageal cancer was found. Conclusion: The above findings indicate that the Asp312Asn and Lys751Gln polymorphisms in the XPD locus are associated with the risk of lung SCC but not lung adenocarcinoma or esophageal SCC in this Chinese population.

关 键 词：北京地区 汉族人群 DNA修复基因 XPD 单核苷酸 多态性 肺癌 食管癌 

分 类 号：R730.2[医药卫生—肿瘤]