原发性肺癌GSTM1基因多态性与化疗效果关系的研究

The Relationship between Genetic Polymorphism of GSTM1 and the Outcome of Chemotherapy in Chinese Patients with Primary Lung Cancer

背景与目的GSTM1参与环境污染物如苯丙芘和其它多环芳烃及抗癌药等的代谢，其多态性是否会影响肺癌患者的化疗效果及预后，国内相关研究比较少，本研究旨在揭示GSTM1多态性是否与化学药物治疗的敏感性有关以及对患者愈后的影响。方法采用聚合酶链反应技术，检测接受化学药物治疗的137例原发性肺癌患者GSTM1基因型频率分布情况。结果137例肺癌患者GSTM1缺陷型频率为58.4％（80／137），功能型频率为41．6％（57／137）；化疗有效组GSTM1缺陷型频率为69．05％（58／84），化疗无效组GSTM1缺陷型频率为41．51％（22／53），二者有统计学差异（P=0．001）。采用铂类化疗方案的患者，化疗有效组GSTM1缺陷型频率为65．43％（53／81），化疗无效组GSTM1缺陷型频率为42％（21／50），二者有统计学差异（P=0．0025）。对于进展期患者化疗有效组GSTM1缺陷型频率为70．13％（54／77），化疗无效组GSTM1缺陷型频率为41．51％（22／53），二者有显著性差异（P=0．001）。当化疗有效时携带GSTM1功能型的鳞癌、小细胞癌患者生存时间（中位生存期分别为42个月和14个月）比携带GSTM1缺陷型的鳞癌、小细胞癌患者长（中位生存期分别为6个月和7个月）（P〈0．05）；而腺癌患者，携带GSTM1功能型和缺陷型的生存时间（中位生存期分别为13个月和11个月）差异无统计学意义（P〉0．05）。对于化疗无效的患者，不论GSTM1为何种基因型、病理分型如何，患者中位生存期均比较接近，生存时间无统计学差异（P〉0．05）。结论GSTM1缺陷型的患者接受化学药物治疗的效果比GSTM1功能型的患者好；采用铂类化疗方案时GSTM1缺陷型的患者化疗效果比GSTM1功能型的患者好。当化疗有效时，患者生存时间与病理分型、GSTM1基因型相关。

Background and objective GSTM1 takes part in the metabolism of environmental pollutants such as benzopyrene, other polycyclic aromatic hydrocarbons and anticancer drugs and so on. The study aims to investigate the relationship between the gene polymorphism of GSTM1 and chemotherapy as well as to study the effect to survival of Chinese patients with lung cancer. Methods The genotype of GSTM1 was examined with a polymerase chain reaction in 137 primary lung cancer patients accepted chemotherapy. Results GSTMI-null genotype frequency was 58.4%（80/137）. The frequency of non-null GSTM1 genotype was 41.6% （57/137） . The frequency of GSTM1-null genotype was 69.05%（58 / 84） in the response group of chemotherapy and 41.51%（22/53） in the non-response group of chemotherapy. They were significantly different （P=0.001）. In the patients with platinum chemotherapy, the frequency of GSTM1-null genotype was 65.43%（53/81） in the response group of chemotherapy and 42%（21/50） in the non-response group. There were stastically differences in them （P=0.0025）. For the advanced cases, GSTM1-null genotype frequency was 70.13% （54/77） in the response group of chemotherapy, 41.51% （22/53） in the non-response group of chemotherapy respectively and they were significantly different （P=0.001） . When the chemotherapy was effective, the survival time of patients in squamous carcinoma and small cell carcinoma with non-null GSTM1 genotype （the median survival times were 42 months and 14 months respectively） were longer than those with null GSTM l genotype （the median survival times were 6 months and 7 months respectively） （P〈0.05） ; The survival times of adencarcinoma with non-null GSTMI genotype and null GSTM1 genotype （the median survival times were 13 months and 11months respectively） were comparative （P〉0.05） . When chemotherapy was not effective, the median survival times were not significantly different （P〉0.05） . Conclusions The effect of chemotherapy of GSTM1-null genotype patients was better than that of GSTMl-postive genotype patients. The chemotherapy effect of the cases with null GSTMI type was better than those with non-null GSTM1 type when the patients accepted platinum chemotherapy. When the chemotherapy was effective, the survival time may be related to the histology types and GSTM1 genotypes.