Objective:Oral fluoropyrimidine S-1 contains tegafur,gimeracil,and oteracil;among them,tegafur is the major active pre-cursor,which is metabolized to 5-fluorouracil by cytochrome P4502A6(CYP2A6).We examined the associations between CYP2A6 poly-morphisms and the treatment outcomes of adjuvant S-1 in patients with gastric cancer.Methods:Two hundred patients diagnosed with pathological stageⅡ-Ⅲgastric cancer were included in this study,and they received adjuvant S-1(40 mg/m2,bid,days 1-28,ev-ery 6 weeks for eight cycles)after curative surgery.Additionally,we analyzed the wild-type allele(W)(CYP2A6*1)and four variant al-leles(V)(CYP2A6*4,*7,*9,and*10).Results:Two hundred patients were enrolled in this study between November 2007 and July 2013.With a median follow-up of 46.4 months(range:12.5-80.1),the 3-year relapse-free survival(RFS)and overall survival(OS)rates were 83.1%(95% confidence interval(CI),77.7%-88.5%)and 94.8%(95% CI,91.6%-98.0%),respectively.However,RFS differed signifi cantly according to the CYP2A6 genotype.The 3-year RFS rates were 95.9% for W/W,83.1% for W/V,and 72.5% for V/V(P=0.032)gen-otypes.Grades 3 and 4 overall toxicity did not differ according to genotype for any grade(P=0.628 and P=0.227,respectively).Conclu-sions:CYP2A6 genotypes correlate with the outcome of S-1 chemotherapy,wherein patients with the variant genotypes show worse prognosis.Additionally,polymorphism detection may be used as a biomarker to guide clinical chemotherapy choices for adjuvant ad-ministration of gastric cancer therapy.%目的:S-1(替吉奥)的活性前体为替加氟,主要通过细胞色素P450酶2A6(human cytochrome P450,family 2,subfamily A, polypeptide 6,CYP2A6)代谢为5-FU而发挥细胞毒作用.本研究探讨CYP2A6基因多态性与胃癌术后患者含S-1辅助化疗方案疗效的相关性.方法:选取2007年11月至2013年5月于郑州市人民医院收治的胃癌患者200例,给予标准给药方案.在CYP2A6基因分析中,选取野生型的CYP2A6*1,突变型的CYP2A6*4、*7、*9、*10等位点进行分析.结果:200例患者中位随访时间为46.4(12.5~80.1)个月.野生型(W/W)3年无复发生存(relapse free survival,RFS)率为95.9%、突变杂合子(W/V)型为83.1%、突变纯合子(V/V)型为72.5%(P=0.032).不同基因型之间的3~4级不良反应的差异无统计学意义(P=0.628,P=0.227).结论:CYP2A6基因型与含S-1化疗方案的长期疗效有关,突变型患者的3年RFS降低.
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