CYP2A6 和 ERCC1 多态性与 S-1 联合顺铂治疗转移性胃癌患者的疗效相关。
CYP2A6 and ERCC1 polymorphisms correlate with efficacy of S-1 plus cisplatin in metastatic gastric cancer patients.
机构信息
Center for Gastric Cancer, Research Institute and Hospital, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi, 410-769, Republic of Korea.
出版信息
Br J Cancer. 2011 Mar 29;104(7):1126-34. doi: 10.1038/bjc.2011.24. Epub 2011 Mar 1.
BACKGROUND
We evaluated the association between polymorphisms of cytochrome P450 2A6 (CYP2A6)/excision repair cross-complementation group 1 (ERCC1)/X-ray repair cross-complementing group 1(XRCC1) and treatment outcomes of metastatic gastric cancer (MGC) patients treated with S-1/cisplatin.
METHODS
Among MGC patients (n=108), who received S-1 (40 mg m(-2) b.i.d., days 1-14) and cisplatin (60 mg m(-2), day 1) every 3 weeks, we analysed the wild-type allele (W) and variants (V) of CYP2A6 (*4, *7, *9, *10), and the polymorphisms of ERCC1 (rs11615, rs3212986) and XRCC1 (rs25487).
RESULTS
Patients having fewer CYP2A6 variants had better response rates (W/W vs W/V other than *1/*4 vs V/V or *1/*4=66.7 vs 58.3 vs 32.3%; P=0.008), time to progression (TTP) (7.2 vs 6.1 vs 3.5 months, P=0.021), and overall survival (23.2 vs 15.4 vs 12.0 months, P=0.004). ERCC1 19442C>A (rs3212986) was also associated with response rate (C/C, 46.7% vs C/A, 55.3% vs A/A, 87.5%) (P=0.048) and TTP (4.4 vs 7.6 vs 7.9 months) (P=0.012). Patients carrying both risk genotypes of CYP2A6 (V/V or 1/*4) and ERCC1 19442C>A (C/C) vs those carrying none showed an adjusted odds ratio of 0.113 (P=0.004) for response, and adjusted hazard ratios of 3.748 (P=0.0001) for TTP and 2.961 (P=0.006) for death.
CONCLUSION
Polymorphisms of CYP2A6 and ERCC1 19442C>A correlated with the efficacy of S-1/cisplatin.
背景
我们评估了细胞色素 P450 2A6（CYP2A6）/切除修复交叉互补组 1（ERCC1）/X 射线修复交叉互补组 1（XRCC1）的多态性与接受 S-1/顺铂治疗的转移性胃癌（MGC）患者治疗结果之间的关系。
方法
在接受 S-1（40mg/m(-2) ，bid，第 1-14 天）和顺铂（60mg/m(-2) ，第 1 天）每 3 周治疗的 MGC 患者（n=108）中，我们分析了 CYP2A6（*4、*7、*9、*10）的野生型等位基因（W）和变体（V），以及 ERCC1（rs11615、rs3212986）和 XRCC1（rs25487）的多态性。
结果
具有较少 CYP2A6 变体的患者具有更好的缓解率（W/W 比 W/V 以外的 *1/*4 比 V/V 或 *1/*4=66.7%比 58.3%比 32.3%；P=0.008）、疾病进展时间（TTP）（7.2 比 6.1 比 3.5 个月，P=0.021）和总生存期（23.2 比 15.4 比 12.0 个月，P=0.004）。ERCC1 19442C>A（rs3212986）也与缓解率相关（C/C，46.7%比 C/A，55.3%比 A/A，87.5%）（P=0.048）和 TTP（4.4 比 7.6 比 7.9 个月）（P=0.012）。同时携带 CYP2A6（V/V 或 1/*4）和 ERCC1 19442C>A（C/C）两种风险基因型的患者与不携带任何一种基因型的患者相比，缓解的调整优势比为 0.113（P=0.004），TTP 的调整危险比为 3.748（P=0.0001），死亡的调整危险比为 2.961（P=0.006）。
结论
CYP2A6 和 ERCC1 19442C>A 的多态性与 S-1/顺铂的疗效相关。
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