胸苷酸合成酶基因多态性与晚期非小细胞肺癌化疗敏感性的关系

摘要

Objective To analyze the association between polymorphisms in thymidylate synthase (TS) and clinical responses to platinum-based chemotherapy in advanced non-small-cell lung cancer (NSCLC). Methods A total of 101 patients with advanced NSCLC were treated with cisplatin- or carboplatin-based chemotherapy, and clinical response was evaluated after 2 to 3 cycles. TS 5'-UTR genotypes were determined by PCR methods. Unconditional logistic regression model was used to analyze the association between genetic polymorphisms and clinical responses. Results The overall response rate ( CR + PR) was 36.7％. The TS 5'-UTR 2R allele carriers had higher response rate than the subjects with the TS 5'-UTR 3P/3R genotype (adjusted OR: 1.54;95％CI=0.65～3.68,P=0.331). The incidence rates of granulocytopenia and vomiting/nausea in 3P/3R genotype were significantly lower than those in the other genotypes (P ＜0. 05). Conclusions TS 5'-UTR polymorphism does not seem to have significant role in susceptibility of platin-based chemotherapy in advanced non-small cell lung cancer.%目的 探讨胸苷酸合成酶(TS)基因多态性与晚期非小细胞肺癌(NSCLC)患者对铂类为基础的化疗敏感性的关系.方法 101例晚期NSCLC患者采用顺铂或卡铂为主的方案化疗,2～3个周期后进行临床疗效评价.应用PCR方法分析患者TS 5'-非翻译区(UTR)基因多态性,以非条件logistic回归模型分析不同基因型与化疗敏感性的关系.结果 101例患者的总有效率为30.7%.携带TS 5'-UTR 2R等位基因患者的化疗敏感性是携带 TS 5'-UTR 3R/3R基因型患者的1.54倍(95%CI=0.65～3.68,P=0.331),但无统计学差异.携带3R/3R基因型患者粒细胞减少和恶心、呕吐的化疗毒性反应程度低于3R/2R和2R/2R基因型患者(P<0.05).结论 TS 5'-UTR基因可能不是NSCLC铂类药物化疗的独立敏感性预测因子.