尿苷二磷酸葡糖醛酸转移酶1A7基因多态与肺癌遗传易感性的关系  

Correlation of Polymorphisms of UDP-Glucuronosyltransferase 1A7 Gene to Genetic Susceptibility of Lung Cancer

作　　者：冯飞跃[1] 梁刚[2] 吕文富[2] 缪小平[2] 于春媛[2] 谭文[2] 周翊峰[2] 孙瞳[2] 康滨[3] 周彤[3] 潘凯枫[3] 张联[3] 林东昕[2] 

机构地区：[1]中国医学科学院中国协和医科大学肿瘤医院胸外科,北京100021 [2]中国医学科学院中国协和医科大学肿瘤医院研究所病因及癌变研究室,北京100021 [3]北京大学医学部临床肿瘤学院北京市肿瘤研究所流行病学研究室,北京100034

出　　处：《癌症》2005年第9期1085-1090,共6页Chinese Journal of Cancer

基　　金：国家杰出青年科学基金(No.39825122);国家"973"肿瘤基础研究项目(No.TG1998051204)~~

摘　　要：背景与目的:代谢酶尿苷二磷酸葡糖醛酸转移酶1A7(UDP-glucuronosyltcansferase,UGT1A7)可催化香烟中的致癌物质苯并[琢]芘、亚硝胺NNK和杂环胺PhIP与葡糖醛酸结合使之失活,在解毒机制中起重要作用。本实验旨在研究UGT1A7基因多态与肺癌易感性的关系。方法:以聚合酶链反应-变性高效液相色谱(DHPLC)技术和聚合酶链反应-限制性片段长度多态性方法,分析317例正常对照和312例肺癌患者外周血淋巴细胞基因组DNA,UGT1A7129～131和208位点多态基因型分布,及其与肺癌风险的关系。结果:与携带UGT1A7*1/*1基因型个体比较,携带UGT1A7*3/*1基因型的个体患肺腺癌的风险增高1.80倍(校正的OR为1.80;95%CI1.03～3.12),携带UGT1A7*3基因型的个体患肺腺癌的风险增高1.59倍(校正的OR为1.59,95%CI0.96～2.63)。UGT1A7多态与肺鳞癌风险不相关。结论:UGT1A7基因多态可能是中国人肺癌遗传易感性因素。BACKGROUND ＆ OBJECTIVE： UDP-glucuronosyltransferase 1A7 （UGT1A7） plays an important role in detoxification through catalyzing combination of glucuronic acid and tobacco carcinogens, including benzo [α] pyrene, nitrosamine, and heterocyclic amine PhlP, therefore, inactivates the carcinogens. This study was to examine the correlation of polymorphisms of UGTlA7 gene to genetic susceptibility of lung cancer. METHODS： Polymorphisms of UGT1A7 gene at 12-131 and 208 sites in peripheral lymph cells of 312 patients and 317 age-and sex-matched controls were detected by polymerase chain reaction-denaturized high performance liquid chromatography （PCR-DHPLC） and potymerase chain reaction-restriction fragment length polymorphism （PCR-RFLP）; the correlation of these polymorphisms to genetic susceptibility of lung cancer was analyzed. RESULTS： Compared with the UGT1A7＊1/＊1 genotype carriers, the UGT1A7 ＊3/＊1 genotype carriers had a 1.80-fold increased risk of lung adenocarcinoma[adjusted odds ratio （OR）, 1.80; 95% confidence interval （CI）, 1.03-3.12], the UGT1A7＊3 genotype carriers had a 1.59-fold increased risk of lung adenocarcinoma （adjusted OR, 1.59; 95% CI, 0.96-2.63）. The UGT1A7 polymorphisms had no correlation with risk of lung squamous cell carcinoma. CONCLUSION： UGT1A7 gene polymorphisms may increase the genetic susceptibility of lung adenocarcinoma in Chinese.

关 键 词：肺肿瘤/遗传学 UGTlA7基因 基因多态 遗传易感性 中国人 

分 类 号：R734.2[医药卫生—肿瘤]