Glutathione-S-transferase P1 isoenzyme polymorphisms, platinum-based chemotherapy, and non-small cell lung cancer
Glutathione-S-transferase P1 isoenzyme polymorphisms, platinum-based chemotherapy, and non-small cell lung cancer
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DOI：
10.1097/01243894-200609000-00013
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发表时间：
2006-09-01
影响因子：
20.4
通讯作者：
Thatcher, Nicholas
中科院分区：
文献类型：
--
作者：
Booten, Richard;Ward, Tim;Thatcher, Nicholas
背景资料：GST（GST 1）的PI同工酶内的多态性与酶活性的改变有关，并可能改变对铂类化疗的敏感性。我们研究了外显子5和外显子6 GSTP 1基因多态性与接受含铂化疗的晚期非小细胞肺癌（NSCLC）患者的治疗反应、血液学和非血液学毒性以及总生存率的关系。方法：2001年至2002年，108例未经化疗的晚期NSCLC患者被招募。分别使用Pearson卡方检验和Kruskal-Wallis检验评价GST 1多态性（Ile 105 Val、Thr 110 Ser、Ala 1 14 Val和Asp 147 Tyr）和GST 1 *A、*B和 *C单倍型与治疗反应和毒性之间的关联。使用Kaplan-Meier生存曲线和考克斯比例风险ratio.Results：GST 1多态性和治疗反应或生存之间没有显着的关联进行了比较与生存。对于具有105 Val等位基因（p = 0.020）或GST 1 *B单倍型（p = 0.038）的患者，证明了显著更少的血小板减少毒性。然而，变异等位基因GSTP 1 105 Val，并拥有GSTP 1 *B等位基因的患者表现出显着的趋势，对低劣的反应和survival.Conclusions：GSTP 1单倍型可用于分层铂类化疗后的血液毒性，但缺乏显着的相关性与反应或生存表明，GSTP 1多态性可能不是强有力的药物基因组学标记在这个人口。纳入GSTP 1单倍型的其他大型前瞻性研究可能会澄清报道的差异。
Background: Polymorphisms within the PI isoenzyme of GST (GSTP1) are associated with alterations in enzyme activity and may change sensitivity to platinum-based chemotherapy. We investigated the relationship between exon 5 and exon 6 GSTP1 gene polymorphisms and treatment response, hematological, and nonhematological toxicity and overall survival for patients receiving platinum-based chemotherapy for advanced non-small cell lung cancer (NSCLC).Methods: Between 2001 and 2002, 108 patients with chemotherapy-naive advanced NSCLC were recruited. Associations between the GSTP1 polymorphisms (Ile105Val, Thr110Ser, Ala1 14Val, and Asp 147Tyr) and GSTP1*A, *B, and *C haplotypes and treatment response and toxicity were evaluated using the Pearson chi(2) and Kruskal-Wallis tests, respectively. Associations with survival were compared using Kaplan-Meier survival curves and Cox proportional hazard ratios.Results: No significant associations were noted between GSTP1 polymorphisms and treatment response or survival. Significantly less neutropenic toxicity was demonstrated for patients possessing the 105Val allele (p = 0.020) or the GSTP1*B haplotype (p = 0.038). However, the variant allele GSTP1 105Val, and patients possessing a GSTP1*B allele demonstrated notable trends toward inferior response and survival.Conclusions: GSTP1 haplotype can be used to stratify hematological toxicity after platinum-based chemotherapy, but the lack of significant associations with response or survival suggests that GSTP1 polymorphisms may not be strong pharmacogenomic markers in this population. Additional large prospective studies incorporating the GSTP1 haplotype may clarify the reported discrepancies.