Li Dairong, Zhou Qinghua, Yuan Tianzhu, Guo Zhanlin, Zhu Wen, Wang Yanping, Chen Xiaohe, Feng Zhihua, Che Guowei
The Key Laboratory of Lung Cancer Molecular Biology of Sichuan Pro- vince, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, P.R.China.
Zhongguo Fei Ai Za Zhi. 2005 Feb 20;8(1):14-9. doi: 10.3779/j.issn.1009-3419.2005.01.03.
Lung cancer is the leading cause of malignant tumor death among Chinese population. It has been known that the development of lung cancer may be associated with genetic po-lymorphism of some lung cancer related genes. The aim of this study is to evaluate the relationship between genetic polymorphism of metabolizing enzymes and susceptibility of lung cancer in Chinese population.
Polymorphism of CYP2E1 RsaI/PstI and GSTM1 was detected in 99 patients with lung cancer and 66 patients with benign pulmonary disease by PCR-RFLP and PCR. The association between genetic polymorphism and susceptibility of lung cancer was analyzed.
No significant difference in three RsaI/PstI genotype distribution of CYP2E1 was found between lung cancer group and control group (Chi-Square=1.374, P=0.241). (2) The frequency of GSTM1-null genotype in lung cancer group was significantly higher than that in control group (57.6% vs 40.9%, Chi-Square=4.401, P=0.036). (3) The individuals who carried with GSTM1-null genotype had a 1.96 fold increased risk of lung cancer (OR=1.96, 95%CI=1.042-3.689, P=0.037) than those who carried with GSTM1-present genotype. (4) When data were stratified by smoking status, the smokers who carried with c1/c1 genotype had a significantly higher risk of lung cancer (OR=3.525, 95%CI=1.168- 10.638, P=0.025) than those never-smokers who carried with at least one c2 allel. (5) When combination of polymorphism of CYP2E1 RsaI/PstI genotype and GSTM1 genotype was analyzed, compared with individuals who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was increased significantly (OR=3.449, 95%CI=1.001- 11.886, P=0.050). Considering smoking status, compared with never-smokers who had concurrent present of GSTM1 and at least one c2 allel genotype, the risk of lung cancer for combination of GSTM1 null and c1/c1 genotype was remarkably increased (OR=11.553, 95%CI=1.068-124.944, P=0.044), as well as that for combination of GSTM1 null and at least one c2 allel genotype (OR=13.374, 95%CI=1.258-142.166, P= 0.032).
(1)GSTM1 null genotype is an important factor associated with increased risk of lung cancer. (2) The combination of c1/c1 and GSTM1-null genotype can remarkably increase risk of lung cancer both in smokers and non-smokers.
肺癌是中国人群恶性肿瘤死亡的首要原因。已知肺癌的发生可能与某些肺癌相关基因的基因多态性有关。本研究旨在评估代谢酶基因多态性与中国人群肺癌易感性之间的关系。
采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）和聚合酶链反应（PCR）技术，检测99例肺癌患者和66例良性肺疾病患者CYP2E1 RsaI/PstI和GSTM1基因多态性。分析基因多态性与肺癌易感性之间的关联。
（1）肺癌组与对照组CYP2E1三种RsaI/PstI基因型分布差异无统计学意义（χ²=1.374，P=0.241）。（2）肺癌组GSTM1缺失基因型频率显著高于对照组（57.6%比40.9%，χ²=4.401，P=0.036）。（3）携带GSTM1缺失基因型个体患肺癌的风险比携带GSTM1存在基因型个体高1.96倍（OR=1.96，95%可信区间=1.042 - 3.689，P=0.037）。（4）按吸烟状况分层分析数据时，携带c1/c1基因型的吸烟者患肺癌风险显著高于携带至少一个c2等位基因的非吸烟者（OR=3.525，95%可信区间=1.168 - 10.638，P=0.025）。（5）分析CYP2E1 RsaI/PstI基因型与GSTM1基因型联合情况时，与同时存在GSTM1和至少一个c2等位基因基因型个体相比，GSTM1缺失与c1/c1基因型联合时肺癌风险显著增加（OR=3.449，95%可信区间=1.001 - 11.886，P=0.050）。考虑吸烟状况，与同时存在GSTM1和至少一个c2等位基因基因型的非吸烟者相比，GSTM1缺失与c1/c1基因型联合时肺癌风险显著增加（OR=11.553，95%可信区间=1.068 - 124.944，P=0.044），GSTM1缺失与至少一个c2等位基因基因型联合时肺癌风险也显著增加（OR=13.374，95%可信区间=1.258 - 142.166，P=0.032）。
（1）GSTM1缺失基因型是与肺癌风险增加相关的重要因素。（2）c1/c1与GSTM1缺失基因型联合可显著增加吸烟者和非吸烟者患肺癌的风险。
