The impact of CYP2A6 polymorphisms on adjuvant S-1 chemotherapy outcomes in pa-tients with curatively resected gastric cancer
10.3969/j.issn.1000-8179.2018.04.989
- VernacularTitle:CYP2A6基因多态性对胃癌术后含S-1辅助化疗方案疗效的影响
- Author:
Guiju LIU
1
;
Jiazhuan MEI
;
Ruijun LI
;
Weijuan LI
Author Information
1. 郑州人民医院肿瘤科 郑州市450000
- Keywords:
CYP2A6;
polymorphism;
gastric cancer;
S-1
- From:
Chinese Journal of Clinical Oncology
2018;45(4):171-178
- CountryChina
- Language:Chinese
-
Abstract:
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.
