Abbas Mohammad, Kushwaha Vandana Singh, Srivastava Kirti, Banerjee Monisha
Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow -226007, Uttar Pradesh, India.
Department of Radiotherapy, King George's Medical University, Lucknow-226003, Uttar Pradesh, India.
PLoS One. 2015 Nov 16;10(11):e0142501. doi: 10.1371/journal.pone.0142501. eCollection 2015.
Cisplatin based concomitant chemoradiation (CRT) is the standard treatment for locally advanced cervical cancer (CC). Glutathione S-transferase (GST), a phase II antioxidant enzyme is induced by oxidative stress generated by drugs and reactive oxidants. The present study was undertaken to evaluate the association of GSTM1, T1 and P1 polymorphisms with the outcome of CRT treatment in CC patients.
A total of 227 cervical cancer patients with stages IIB-IIIB treated with the same chemoradiotherapy regimen were enrolled and genotyped for GSTM1, T1 and P1 gene polymorphisms by multiplex polymerase chain reaction (mPCR) and PCR-restriction fragment length polymorphism (PCR-RFLP). Overall survival was evaluated using Kaplan-Meier survival function and Cox proportional hazards model. All data were analyzed using SPSS (version 21.0).
Stratified analysis showed that GSTM1 null (M1-) genotype was associated with a significantly better survival among patients with stage IIB cervical cancer (log-rank P = 0.004) than cases with stage IIIA/IIIB. Death and recurrence were significantly higher in patients with GSTM1 present genotype (M1+) (P = 0.037 and P = 0.003 respectively) and those with M1- showed reduced hazard of death with an adjusted hazard ratio 'HR' of 0.47 (95% CI, 0.269-0.802, P = 0.006). Women with M1- genotype as well as in combination with GSTT1 null (T1-), GSTP1 (AG+GG) and GSTT1 null/GSTP1 (AG+GG) showed better survival and also reduced risk of death (HR = 0.31, P = 0.016; HR = 0.45, P = 0.013; HR = 0.31, P = 0.02 respectively).
To the best of our knowledge, this is the first study to correlate the association of GSTM1, T1 and P1 gene polymorphisms with treatment outcome of CRT treated CC patients. Our results suggested that individuals with GSTM1 null genotype and in combination with GSTT1 null and GSTP1 (AG+GG) had a survival advantage. Such genetic studies may provide prognostic information in CRT treated CC patients.
基于顺铂的同步放化疗（CRT）是局部晚期宫颈癌（CC）的标准治疗方法。谷胱甘肽S-转移酶（GST）是一种II期抗氧化酶，由药物和活性氧化剂产生的氧化应激诱导产生。本研究旨在评估GSTM1、T1和P1基因多态性与CC患者CRT治疗结果之间的关联。
共纳入227例接受相同放化疗方案治疗的IIB-IIIB期宫颈癌患者，通过多重聚合酶链反应（mPCR）和聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对GSTM1、T1和P1基因多态性进行基因分型。使用Kaplan-Meier生存函数和Cox比例风险模型评估总生存率。所有数据均使用SPSS（版本21.0）进行分析。
分层分析显示，GSTM1缺失（M1-）基因型与IIB期宫颈癌患者（对数秩检验P = 0.004）的生存率显著高于IIIA/IIIB期患者。GSTM1存在基因型（M1+）的患者死亡和复发率显著更高（分别为P = 0.037和P = 0.003），而M1-基因型患者的死亡风险降低，调整后的风险比“HR”为0.47（95% CI，0.269-0.802，P = 0.006）。M1-基因型以及与GSTT1缺失（T1-）、GSTP1（AG+GG）和GSTT1缺失/GSTP1（AG+GG）组合的女性生存率更高，死亡风险也降低（HR = 0.31，P = 0.016；HR = 0.45，P = 0.013；HR = 0.31，P = 0.02）。
据我们所知，这是第一项将GSTM1、T1和P1基因多态性与CRT治疗的CC患者治疗结果相关联的研究。我们的结果表明，GSTM1缺失基因型以及与GSTT1缺失和GSTP1（AG+GG）组合的个体具有生存优势。此类基因研究可能为CRT治疗的CC患者提供预后信息。
