肿瘤易感基因CYP4501A1和GSTm1多态性与高氡暴露地区居民肺癌关系研究

Polymorphisms of the cytochrome P450 and glutathion s-transferase genes associated with lung cancer susceptibility for the residents in high radon-exposed area

目的 研究高氡暴露地区居民肺癌易感基因CYP4501A1和GSTm1多态性的变化规律，探讨这2种基因多态性与肺癌及环境因素之间的关系。方法 按病例一对照的研究方法从甘肃省庆阳地区选择原发性肺癌病例和相匹配的对照人群进行室内氡、钍射气的测量，并应用PCR—RFLP和PCR方法检测2种基因的多态性。结果研究表明，携带杂合型CYP1A1（w/m）或缺失型GSTm1（-）基因与野生型基因的个体比较，肺癌发病风险分别为1.46倍（95％Cl为0．72～2、95）和1.28倍（95％Cl为0.67～2.41）。同时携带两种突变基因型的个体，肺癌发病风险为2、00倍（95％Cl为0．72～5．58），重度吸烟者肺癌的发病风险会增至2、14倍（95％Cl为0.35～13．12）。居住在室内氡、钍射气累积有效剂量50～100mSv并携带突变型CYP1A1（w／m）或GSTm1（-）基因的个体患肺癌的风险分别为2.63倍（95％Cl为0．21～31．34）和3．50倍（95％cl为0.31～39.12）。有肿瘤家族史的人群肺癌发病风险是3．75倍（95％cl为1.51～9.29），差异有统计学意义。结论 杂合型CYP1A1（w／m）和突变型GSTml（-）基因是较重要的肺癌风险因子，尤其在有效剂量50～100mSv和2种突变基因的协同作用时。

Objective To investigate whether the CYP1A1 and GSTml genetic polymorphism are assoaiate with lung cancer in the residents of high radon exposure area. Methods A case-control method was performed, lung cancer and control individials were selected from Qingyang county of Gansu Province. The indoor radon and thoron concentration were measured, CYP1A1 and GSTml genetic polymorphism were detected by PCR-RFLP or muhiplex-PCR. Results The risk of developing lung cancer for people carried with heterozygous CYP1A1 （w/m）and mutation genotype GSTml （-）were 1.46（95% CI 0.72-2.95） and 1.28（95% CI 0.67-2.41） higher than wide type, respectively. The risk of lung career for combination of CYP1 A1 （w/m）and GSTml （-） increased to 2.00 fold （95 % CI 0. 72-5.58）, the heavy smokers who carried with heterozygous of CYP1 A1 （w/m） was 2.14 fold （95 % CI 0. 35 - 13.12 ）. People who carried with heterozygous CYP1 A1 （w/m） or GSTml （-） when effective dose was in 50-100 mSv,lung canser risk will rised to 2.63 fold （95% CI 0.21-31.34） and 3.50 fold（95% Cl 0.31-39.12）. The risk of lung cancer for people from tumors family was 3.75 fold（95% CI 1.51- 9.29） with statistic significance. Conclusions The CYP1A1 （w/m）and GSTml （-） are two more risk factors for lung carcer, specifically when effective dose was in 50-100 mSv and the two gene functions combined together.