CYP2A6基因多态性对胃癌患者术后辅助替吉奥化疗方案临床疗效的影响

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

目的探讨CYP2A6基因多态性和胃癌患者术后辅助含替吉奥（吉美嘧啶和奥替拉西钾组成的复方制剂）化疗方案临床疗效的相关性。方法入组200例病理分期为II～III期的胃癌患者，给予标准替吉奥给药方案（40 mg/m2,每天两次，第1～28天，休息2周，每6周为一个周期，连用8个周期）。对CYP2A6进行基因分型，野生型为CYP2A6＊1，突变型为CYP2A6＊4，＊7，＊9，＊10。结果200例患者的中位的随访时间是46.5个月。野生型的患者（W/W）（n＝49）3年的无复发生存（RFS）率为95.9%，突变杂合子患者（W/V）（n＝94）的为83.1%，突变纯合子患者（V/V）（n＝57）的为72.5%，3组对比差异均具有统计学意义（P＝0.032）。不同基因型患者之间的3级以上血液学不良反应差异无统计学意义（10.2%与14.9%与10.5%，P＝0.628）。结论CYP2A6基因型和替吉奥化疗方案的长期疗效有关，其多态性位点的检测可为胃癌术后辅助化疗患者的化疗方案选择提供个体化的指导。

ObjectiveOral 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/m2, 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）.ConclusionsCYP2A6 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.