[The influence of CYP2A6 polymorphism on adjuvant S-1 chemotherapy outcomes in patients with curatively resected gastric cancer].

Objective: Oral fiuoropyrimidine S-1 contains tegafur, gimeracil, oteracil. Tegafur is the major active prodrug, which is metabolized to 5-Fu by cytochrome P4502A6 (CYP2A6). This research investigated the association between CYP2A6 polymorphisms and treatment outcomes of adjuvant S-1 in gastric cancer patients. Methods: A total of 200 patients diagnosed pathological stage Ⅱ-Ⅲ gastric cancer were included in this study, who were received adjuvant S-1 chemotherapy regimens after curative surgery (40 mg/m(2,) bid, d1-28, rest 2 weeks, every 6 weeks one cycle). Additionally, the wild-type allele (CYP2A6*1) and four variant alleles (CYP2A6*4, *7, *9, *10) were genotyped. Results: A total of 200 patients were enrolled in this study with a median follow-up of 46.5 months. The 3-year recurrence free survival rates were 95.9% for W/W ( n =49), 83.1% for W/V ( n =94), and 72.5% for V/V ( n =57), with significant difference ( P =0.032). Grade ≥3 hematologic toxicities of three genotype groups were without difference (10.2% vs 14.9% vs 10.5%, P =0.628). Conclusions: CYP2A6 genotypes correlate with the survival of S-1 chemotherapy. And its polymorphism detection can provide individualized guidance for adjuvant chemotherapy options in patients with gastric cancer.