Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes
Genetic determinants of lung cancer short-term survival: the role of glutathione-related genes
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DOI：
10.1016/s0169-5002(01)00426-3
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发表时间：
2002-03-01
期刊：
影响因子：
5.3
通讯作者：
Liu, WG
中科院分区：
文献类型：
--
作者：
Yang, P;Yokomizo, A;Liu, WG
目的：肺癌患者的生存率一直很低。谷胱甘肽酶直接参与铂类化合物的代谢，铂类化合物是一类重要的癌症化疗药物。我们检验了编码谷胱甘肽酶的基因可能预测肺癌短期生存的假设。方法：研究了250例原发性肺癌患者谷胱甘肽相关基因座GSTP1、GSTM1、GSTT1和γ - gcs的DNA多态性，这些基因座分别编码谷胱甘肽s -转移酶pi、谷胱甘肽s -转移酶mu、谷胱甘肽s -转移酶θ和γ -谷氨酰半胱氨酸合成酶。采用Pearson χ 2检验、Kaplan-Meier生存曲线、log rank检验和Cox回归模型进行分析。结果：本研究中有150名（60%）男性和100名（40%）女性。17%的患者从未吸烟，61%的患者在肺癌诊断前至少6个月停止吸烟。在从不吸烟者中，null (N)或low (L)基因型的患者比阳性(P)或high (H)基因型的患者有更好的1年生存率。将两个位点（PP或PH）的P或H患者与一个或两个位点（其他）的N或L患者进行比较。在从不吸烟者中，PP或PH基因型患者的1年生存率为60-78%，而其他基因型患者的1年生存率为89-100%。晚期NL或NN患者的生存优势大于低期患者。在吸烟者中没有观察到类似的结果。结论：谷胱甘肽相关基因可能决定肺癌的生存。我们的研究结果，如果得到证实，将为加强癌症治疗提供新的方向，并为临床医生计划患者特异性治疗提供容易测量的标记。(C) 2002爱思唯尔科学爱尔兰有限公司版权所有。
Purpose: Survival of lung cancer patients has been dismal. Glutathione enzymes are directly involved in the metabolism of platinum compounds, a group of important chemotherapeutic drugs in cancer treatment. We tested the hypothesis that genes encoding glutathione enzymes may predict lung cancer short-term survival. Methods: We studied DNA polymorphisms of 250 primary lung cancer patients at four glutathione-related loci: GSTP1, GSTM1, GSTT1 and gamma-GCS that encode glutathione-S-transferase-pi, glutathione-S-transferase-mu, gluathione-S-transferase-theta, and gamma-glutamylcysteine synthetase, respectively. Pearson's chi(2)-square tests, Kaplan-Meier survival curves, log rank tests, and Cox regression models were applied in the analysis. Results: There were 150 (60%) men and 100 (40%) women in this study. Seventeen percent of the patients had never smoked cigarettes, and 61% had stopped smoking at least 6 months prior to their lung cancer diagnosis. Among never smokers, those with null (N) or low (L) genotype experienced a better 1-year-survival rate than those with a positive (P) or high (H) genotype. Patients with P or H at two loci (PP or PH) were compared with patients with N or L at one or both loci (other). Among never smokers, 1-year-survival rates were 60-78% for patients with PP or PH genotypes compared with 89-100% for other types. The survival advantage was greater among advanced-stage patients who were NL or NN than low-stage patients. Similar results were not observed among smokers. Conclusions: Glutathione-related genes may determine lung cancer survival. Our results, if confirmed, would suggest new directions to enhance cancer treatment, and provide easily measurable markers for clinicians to plan patient-specific therapy. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.