Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)--novel predictors for response and survival in gastric cancer patients.
Polymorphisms of glutathione S-transferases (GST) and thymidylate synthase (TS)--novel predictors for response and survival in gastric cancer patients.
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DOI：
10.1038/sj.bjc.6602891
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发表时间：
2006-01-30
影响因子：
8.8
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中科院分区：
文献类型：
--
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目的探讨5-氟尿嘧啶(5-FU)和顺铂代谢相关基因多态性对进展期胃癌患者临床预后的预测价值。本研究共纳入52例患者。从石蜡包埋的肿瘤标本中提取DNA。采用聚合酶链式反应-限制性片段长度多态性方法进行基因分型。中位生存期为6.0个月(95%可信区间为3.9；8.1)。总有效率为26%。携带谷胱甘肽S转移酶P1-105Valine/Valine(GSTP1-105VV)基因的患者有效率为67%，而携带至少一个GSTP1-105异亮氨酸(GSTP1-105I)等位基因的患者有效率为21%(P=0.038)。GSTP1-105VV患者的中位生存期为15.0个月(95%可信区间7.8；22.0)，而至少有一个等位基因携带者的中位生存期为6.0个月(95%可信区间5.1；7.0)(P=0.037)。胸腺嘧啶酸合成酶(2R/2R、2R/3RC、3RC/3RC)基因携带者的生存时间为10.2个月(95%CI 5.1；15.3)，而TS基因携带者为6.0个月(95%CI 5.0；7.0)(P=0.099)。携带GSTP1105VV或TS不良基因型的患者中位生存期为6.0月(95%CI3.9；8.1)，而携带GSTP1105VV或TS不良基因型的患者中位生存期为11个月(95%CI6，23；1577)(P=0.044)。通过检测TS和GSTP1基因的多态性，可以确定哪些胃癌患者将受益于5-FU/顺铂化疗，从而避免了其他患者的副作用。
To evaluate the predictive value of a panel of gene polymorphisms involved in metabolism of 5-FU and cisplatin on clinical outcome in advanced gastric cancer patients. A total of 52 patients were enrolled in this study. DNA was extracted from paraffin-embedded tumour specimen. Genotypes were determined using PCR-RFLP. Median survival time was 6.0 months (95% CI 3.9;8.1). Overall response rate was 26%. Patients possessing the glutathione S-transferase P1-105 Valine/Valine (GSTP1-105VV) genotype showed a response rate of 67% compared to 21% in patients harbouring at least one GSTP1-105 Isoleucine (GSTP1-105I) allele (P=0.038). GSTP1-105VV patients demonstrated a significant superior median survival time of 15.0 months (95% CI 7.8;22.0) compared to 6.0 months (95% CI 5.1;7.0) in patients with at least one GSTP1-105I allele (P=0.037). Patients possessing a favourable thymidylate synthase (TS) genotype (2R/2R, 2R/3RC, 3RC/3RC) experienced a superior survival time of 10.2 months (95% CI 5.1;15.3) compared to 6.0 months (95% CI 5.0;7.0) in patients with unfavourable TS genotypes (P=0.099). Patients harbouring the GSTP1-105II genotype and one of the unfavourable TS genotypes showed an inferior median survival time of 6.0 months (95% CI 3.9;8.1) compared to 11 months (95% CI 6,23;15,77) in patients with either GSTP1-105VV or a favourable TS genotype (P=0.044). Testing for TS and GSTP1 polymorphisms may allow identification of gastric cancer patients who will benefit from 5-FU/cisplatin chemotherapy, sparing others the side effects of this chemotherapy.
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