Yang Ping, Mandrekar Sumithra J, Hillman Shauna H, Allen Ziegler Katie L, Sun Zhifu, Wampfler Jason A, Cunningham Julie M, Sloan Jeff A, Adjei Alex A, Perez Edith, Jett James R
College of Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Thorac Oncol. 2009 Apr;4(4):479-85. doi: 10.1097/jto.0b013e31819c7a2c.
We evaluated the role of glutathione-related genotypes on overall survival, time to progression, adverse events, and quality of life (QOL) in stage IIIB/IV non-small cell lung cancer patients who were stable or responding from initial treatment with platinum-based chemotherapy and subsequently randomized to receive daily oral carboxyaminoimidazole or a placebo.
Of the 186 total patients, 113 had initial treatment with platinum therapy and DNA samples of whom 46 also had QOL data. These samples were analyzed using six polymorphic DNA markers that encode five important enzymes in the glutathione metabolic pathway. Patient QOL was assessed using the Functional Assessment of Cancer Therapy-Lung and the UNISCALE QOL questionnaires. A clinically significant decline in QOL was defined as a 10% decrease from baseline to week-8. Multivariate analyses were used to evaluate the association of the genotypes on the four endpoints.
Patients carrying a GCLC 77 genotype had a worse overall survival (hazard ratio (HR) = 1.5, p = 0.05). Patients carrying the GPX1-CC genotype had a clinically significant decline in the UNISCALE (odds ratio (OR): 7.5; p = 0.04), total Functional Assessment of Cancer Therapy-Lung score (OR: 11.0; p = 0.04), physical (OR: 7.1; p = 0.03), functional (OR: 5.2; p = 0.04), and emotional well-being constructs (OR: 23.8; p = 0.01).
Genotypes of glutathione-related enzymes, especially GCLC, may be used as host factors in predicting patients' survival after platinum-based chemotherapy. GPX1 may be an inherited factor in predicting patients' QOL. Further investigation to define and measure the effects of these genes in chemotherapeutic regimens, drug toxicities, disease progression, and QOL are critical.
我们评估了谷胱甘肽相关基因型对IIIB/IV期非小细胞肺癌患者总生存期、疾病进展时间、不良事件和生活质量（QOL）的作用，这些患者在接受铂类化疗初始治疗后病情稳定或有反应，随后被随机分配接受每日口服羧基氨基咪唑或安慰剂。
在总共186例患者中，113例接受了铂类治疗，其中46例患者还拥有生活质量数据。使用六个多态性DNA标记对这些样本进行分析，这些标记编码谷胱甘肽代谢途径中的五种重要酶。使用癌症治疗-肺癌功能评估和UNISCALE生活质量问卷对患者的生活质量进行评估。生活质量临床上的显著下降定义为从基线到第8周下降10%。采用多变量分析评估基因型与四个终点之间的关联。
携带GCLC 77基因型的患者总生存期较差（风险比（HR）=1.5，p = 0.05）。携带GPX1 - CC基因型的患者在UNISCALE量表（优势比（OR）：7.5；p = 0.04）、癌症治疗-肺癌功能评估总分（OR：11.0；p = 0.04）、身体（OR：7.1；p = 0.03）、功能（OR：5.2；p = 0.04）和情绪健康指标（OR：23.8；p = 0.01）方面有临床上的显著下降。
谷胱甘肽相关酶的基因型，尤其是GCLC，可能作为宿主因素用于预测铂类化疗后患者的生存期。GPX1可能是预测患者生活质量的一个遗传因素。进一步研究以确定和衡量这些基因在化疗方案、药物毒性、疾病进展和生活质量方面的影响至关重要。
