Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma
Influence of GSTP1 I105V polymorphism on cumulative neuropathy and outcome of FOLFOX-4 treatment in Asian patients with colorectal carcinoma
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DOI：
10.1111/j.1349-7006.2009.01418.x
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发表时间：
2010-02-01
期刊：
影响因子：
5.7
通讯作者：
Wang, Wei-Shu
中科院分区：
文献类型：
--
作者：
Chen, Yen-Chung;Tzeng, Cheng-Hwai;Wang, Wei-Shu
谷胱甘肽S-转移酶P1（GSTP 1）参与可能改变铂类化疗疗效和毒性的潜在遗传毒性化合物的解毒。我们分析了166例接受一线FOLFOX 4治疗的中国转移性结直肠癌患者中GSTP 1 I105 V多态性对临床病理特征和结局的影响。还进行了GSTP 1 I105 V、ERCC 1 -118和XPD-751多态性的联合分析。结果表明，与高加索人群相比，Val 105等位基因变异的患病率显著较低（24.7%）。携带Val 105等位基因变异的患者对FOLFOX-4的应答率更高（56.1% vs 37.6%，P = 0.04），无进展生存期（P < 0.01）和总生存期（P <0.01）更长。经校正分析，该多态性被确定为独立的预后因素（P = 0.01）。在联合分析中，没有任何风险基因型的患者，包括GSTP 1 -105 Ile/Ile，ERCC 1 -118 C/T或T/T，和XPD-751 Lys/Gln，具有显著更长的无进展生存期和总生存期（P < 0.01）。此外，Val 105等位基因变异的患者在不同治疗周期后3/4级累积神经病变的发生率更高。这些数据表明，亚洲人群有较低的患病率在GST 1的I105 V多态性。GST 1中的I105 V多态性通过降低其酶活性和随后对奥沙利铂的解毒作用，可能是FOLFOX- 4治疗结局更好但神经毒性更大的关键决定因素。（Cancer Sci 2010; 101：530-535）
Glutathione S-transferase P1 (GSTP1) participates in detoxification of potentially genotoxic compounds that may alter the efficacy and toxicity of platinum-based chemotherapy. We analyzed the influence of I105V polymorphism of GSTP1 on clinico-pathological features and outcomes in 166 Chinese patients with metastatic colorectal carcinoma who had been treated with first-line FOLFOX4. Combined analysis of GSTP1 I105V, ERCC1-118, and XPD-751 polymorphisms was also conducted. The results showed that, in comparison with Caucasian populations, a remarkably lower prevalence of Val105 allele variants was noted (24.7%). Patients with Val105 allele variants had a higher response to FOLFOX-4 (56.1% vs 37.6%, P = 0.04), and a longer progression-free (P < 0.01) as well as overall ( P < 0.01) survival. By adjusted analysis, this polymorphism was identified as an independent prognostic factor (P = 0.01). In combined analysis, patients without any risk genotype, including GSTP1-105 Ile/Ile, ERCC1-118 C/T or T/T, and XPD-751 Lys/Gln, had significantly longer progression-free and overall survivals (P < 0.01). In addition, patients with Val105 allele variants had a higher incidence of grade 3/4 cumulative neuropathy after different cycles of treatment. These data suggest that Asian populations have a lower prevalence of I105V polymorphism in GSTP1. I105V polymorphism in GSTP1, by reducing its enzymatic activity and consequential detoxification to oxaliplatin, could be a key determinant for a better outcome, but more neurotoxicity, to FOLFOX- 4 treatment. (Cancer Sci 2010; 101: 530-535)