Cell Biology Laboratory, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, No 97 Ma Chang, Tongzhou District, Beijing 101149, China.
Lung. 2012 Feb;190(1):91-8. doi: 10.1007/s00408-011-9338-8. Epub 2011 Nov 23.
Studies of polymorphisms in CYP1A1, CYP2E1, CYP2D6, and GSTM1 and their relationship to lung cancer susceptibility and chemotherapy response have been reported, but the results are not consistent. In this study we selected four polymorphisms in these genes, several of which have previously been researched, and investigated their association with lung cancer susceptibility and chemotherapy response.
We genotyped the four polymorphisms in a cohort composed of 217 non-small-cell lung cancer (NSCLC) patients and 198 controls. Of these, 145 advanced NSCLC patients underwent chemotherapy and were monitored for 5 years.
Significant differences in the GSTM1 polymorphism were observed between the case and control groups (P = 0.02). We observed a synergistic effect of smoking and GSTM1. Smokers with deficient-type GSTM1 had a 4.96-fold increased risk of developing lung cancer. Significant differences in GSTM1 and CYP1A1 polymorphisms were observed between the response and nonresponse groups (P = 0.004 and P = 0.026). Moreover, patients with deficient-type GSTM1 were superior responders to platinum drugs than those carrying wild-type GSTM1 (P = 0.014). In addition, patients carrying TT CYP1A1 responded better to nonplatinum drugs than those carrying TC and CC CYP1A1 (P = 0.01). Polymorphisms in the four enzymes had no effect on the overall survival of NSCLC patients.
Our findings support the hypothesis that a polymorphism in GSTM1 is associated with lung cancer susceptibility. Furthermore, polymorphisms in GSTM1 and CYP1A1 were associated with chemotherapy response. In particular, smokers carrying deficient-type GSTM1 were at a higher risk of developing lung cancer. Patients carrying deficient-type GSTM1 responded better to platinum drugs, while those with TT CYP1A1 were better responders to nonplatinum drugs.
已有研究报道细胞色素 P4501A1（CYP1A1）、细胞色素 P4502E1（CYP2E1）、细胞色素 P4502D6（CYP2D6）和谷胱甘肽 S-转移酶 M1（GSTM1）的多态性与其患肺癌的易感性和化疗反应的关系，但结果并不一致。本研究选择了这 4 个基因中的 4 个多态性，其中一些多态性之前已有研究，并探讨了它们与肺癌易感性和化疗反应的关系。
我们对由 217 例非小细胞肺癌（NSCLC）患者和 198 例对照组成的队列进行了这 4 个多态性的基因分型。其中，145 例晚期 NSCLC 患者接受了化疗，并进行了 5 年的监测。
病例组和对照组之间 GSTM1 多态性有显著差异（P = 0.02）。我们观察到吸烟和 GSTM1 之间存在协同作用。缺乏型 GSTM1 的吸烟者患肺癌的风险增加了 4.96 倍。反应组和无反应组之间 GSTM1 和 CYP1A1 多态性有显著差异（P = 0.004 和 P = 0.026）。此外，缺乏型 GSTM1 的患者对铂类药物的反应优于携带野生型 GSTM1 的患者（P = 0.014）。此外，携带 TT CYP1A1 的患者对非铂类药物的反应优于携带 TC 和 CC CYP1A1 的患者（P = 0.01）。这 4 种酶的多态性对 NSCLC 患者的总生存无影响。
我们的研究结果支持 GSTM1 多态性与肺癌易感性相关的假说。此外，GSTM1 和 CYP1A1 多态性与化疗反应相关。特别是携带缺乏型 GSTM1 的吸烟者患肺癌的风险更高。携带缺乏型 GSTM1 的患者对铂类药物反应更好，而 TT CYP1A1 携带者对非铂类药物反应更好。
