髓过氧化物酶基因-463 G/A多态与中国人肺癌遗传易感性

Lung cancer risk associated with genetic polymorphism in myeloperoxidase (-463 G/A) in a Chinese population

目的 研究髓过氧化物酶 (MPO)基因 46 3G→A单核苷酸多态与肺癌易感性的关系。方法 以PCR 单链构像多态 (SSCP)技术 ,分析了 314例肺癌患者和 32 0例正常对照者MPO基因启动子区第 46 3位核苷酸多态基因型分布 ,及其与肺癌风险的关系。结果 正常对照组中G和A等位基因频率分别为 85 .0 %和 15 .0 % ,而肺癌患者分别为 89.0 %和 11.0 %。携带MPO 46 3GG基因型的个体患肺癌风险比携带GA和AA基因型个体高 1.7倍 (校正的OR为 1.7;95 %CI为 1.2～ 2 .5 ) ,且此种风险增高只限于肺鳞癌 (OR为 2 .4;95 %CI为 1.4～ 3.9) ,而与肺腺癌无关 (OR为 1.3;95 %CI为0 .8～ 2 .1)。分层分析结果表明 ,与GA和AA基因型比较 ,GG基因型并不增加非吸烟者和累积吸烟量 <2 6包年者患肺癌的风险。但在累积吸烟量≥ 2 6包年的吸烟者中 ,GG基因型发生肺鳞癌的风险比GA和AA基因型高 3.3倍。结论 MPO 46 3A等位基因显著降低中国人发生吸烟相关性肺鳞癌的风险。

Objective To examine the relationship between susceptibility to lung cancer among Chinese and genetic polymorphism at nucleotide -463 (G/A) in myeloperoxidase (MPO), an enzyme found in lysosomes of phagocytes and involved in the formation of hydroxyl radicals and activation of various smoking-related carcinogens. Methods The association of this polymorphism with lung cancer in a hospital-based case-control study of 314 patients and 320 age- and sex-matched controls was tested. The MPO genotypes were determined by polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP). Results The allele frequency for MPO-463A was found to be 11.0% for controls, compared with 15.0% for patients. Multivariate analysis showed an increased risk for overall lung cancer in subjects having GG genotype ( OR , 1.7; 95% CI , 1.2-2.5), however, the elevated risk was limited to squamous cell carcinoma ( OR , 2.4; 95% CI , 1.4-3.9; n =177) but not to adenocarcinoma ( OR , 1.3; 95% CI , 0.8-2.1; n =137). In addition, the risky effect of the GG genotype on squamous cell carcinoma of the lung was evident only in the smokers and those who smoked ≥26 pack-years ( OR , 20.5; 95% CI , 5.6-75.3) as compared with GA and AA genotypes ( OR , 6.2; 95% CI , 1.7-22.5) but not in the nonsmokers or those who smoked <26 pack-years. Conclusion Our data support the hypothesis that -463A polymorphism in the MPO gene may reduce the susceptibility to lung cancer in the Chinese.