Objective   Oral fluoropyrimidine S‐1 contains tegafur, gimeracil, and oteracil; among them, tegafur is the major active precursor, which is metabolized to 5‐fluorouracil by cytochrome P4502A6 (CYP2A6). We examined the associations between CYP2A6 polymorphisms and the treatment outcomes of adjuvant S-1 in patients with gastric cancer.

  Methods   Two hundred patients diagnosed with pathological stage Ⅱ-Ⅲ gastric cancer were included in this study, and they received adjuvant S-1 (40 mg/m², bid, days 1-28, every 6 weeks for eight cycles) after curative surgery. Additionally, we analyzed the wild-type allele (W) (CYP2A6^*1) and four variant alleles (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) genotypes. Grades 3 and 4 overall toxicity did not differ according to genotype for any grade (P=0.628 and P=0.227, respectively).

  Conclusions   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 administration of gastric cancer therapy.