Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients.
Glutathione S-transferase M1, T1, and P1 polymorphisms and survival among lung cancer patients.
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发表时间：
2003-06
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通讯作者：
C. Sweeney;V. Nazar‐Stewart;P. Stapleton;D. Eaton;T. Vaughan
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作者：
C. Sweeney;V. Nazar‐Stewart;P. Stapleton;D. Eaton;T. Vaughan
谷胱甘肽S-转移酶（GST）酶解毒治疗药物和反应性氧化剂，因此GST多态性可能会影响癌症诊断后的生存率。我们根据GST多态性在一系列以人群为基础的肺癌患者中评估生存率。研究对象（n = 274）是1993年至1996年诊断为肺癌的男性，他们参加了一项病例对照研究，并提供了用于基因分型的血液样本。多重PCR检测GSTM 1和GSTT 1基因的存在。通过PCR和寡核苷酸连接试验确定GST 1 Ile（105）瓦尔取代的基因型。研究对象的生命状态随访至2000年，总生存率采用Kaplan-Meier生存函数和考克斯比例风险模型进行评估。GSTM 1无效基因型受试者的生存期较短; GSTM 1无效受试者5年生存率为0.20 [95%置信区间（CI）0.14-0.27]，而GSTM 1存在受试者为0.29（95% CI 0.22-0.37）。经诊断时分期和组织学校正后，GSTM 1缺失基因型相关死亡的相对风险为1.36，95%CI 1.04-1.80。在整个研究人群中，GSTT 1或GSTP 1基因型与生存率之间没有关联，在接受化疗的患者亚组中也没有关联（n = 130）。对于GSTM 1，我们的结果与以前的研究一致，该研究还观察到GSTM 1-null基因型（赋予肺癌易感性）与较短的生存期相关。未来肺癌生存率的研究应考虑GSTM 1基因型以及调查潜在的机制。
Glutathione S-transferase (GST) enzymes detoxify therapeutic drugs and reactive oxidants, so GST polymorphisms may influence survival after diagnosis of cancer. We evaluated survival according to GST polymorphisms in a population-based series of lung cancer patients. The study subjects (n = 274) were men diagnosed with lung cancer from 1993 through 1996 who participated in a case control study and provided a blood sample for genotyping. The presence of the GSTM1 and GSTT1 genes were assayed by multiplex PCR. Genotype at the GSTP1 Ile(105)Val substitution was determined by PCR and oligonucleotide ligation assay. The study subjects were followed for vital status through 2000, and overall survival was evaluated in Kaplan-Meier survival functions and Cox proportional hazards models. Subjects with the GSTM1 null genotype had shorter survival; the proportion of GSTM1 null subjects surviving at 5 years was 0.20 [95% confidence interval (CI) 0.14-0.27], compared with 0.29 (95% CI 0.22-0.37) for GSTM1 present subjects. The relative risk of death associated with GSTM1 null genotype, adjusted for stage at diagnosis and histology, was 1.36, 95% CI 1.04-1.80. There was no association between GSTT1 or GSTP1 genotype and survival in the overall study population, nor in a subgroup of patients treated with chemotherapy (n = 130). For GSTM1, our results are consistent with a previous study, which also observed that the GSTM1-null genotype, which confers susceptibility to lung cancer, was associated with shorter survival. Future studies of lung cancer survival should take into account GSTM1 genotype as well as investigate underlying mechanisms.