ABCB1 G2677T/A多态性与进展期胃癌患者紫杉醇治疗敏感性的关系

Association between ABCB1 G2677T/A polymorphisms and chemosensitivity of paclitaxel in advanced gastric cancer

目的：探讨ABCB1多态性与进展期胃癌患者紫杉醇治疗敏感性的关系。方法回顾性收集2008年12月至2013年4月间北京大学肿瘤医院连续收治的412例采用紫杉醇联合卡培他滨（紫杉醇组，268例）或顺铂联合卡培他滨（顺铂组，144例）一线化疗的进展期胃癌患者的临床资料及患者化疗前的外周血。采用PCR扩增联合Sanger测序方法检测ABCB1 G2677T／A多态性，根据RECIST1．1标准判断患者临床疗效，通过分析ABCB1 G2677T／A多态性与患者疗效及其预后的关系，进而评价ABCB1 G2677T／A多态性与紫杉醇治疗敏感性的关系。结果所有患者均进行了ABCB1 G2677T／A基因分型检测，其中野生型基因型频率（G2677G）为22．8％（94／412），单等位基因突变型（G2677T和G2677A）的频率为49．8％（205／412），双等位基因突变型（T2677T、T2677A和A2677A）为27．4％（113／412）。在紫杉醇组中，ABCB1 G2677T／A单等位基因突变型的患者疾病控制率（DCR）[89．9％（116／129）]和中位无进展生存时间（PFS，190 d）均明显高于野生型[76．1％（51／67）及110 d，均P＜0．05]，而与双等位基因突变型患者的差异无统计学意义。而在顺铂组中，ABCB1 G2677T／A基因型间DCR和中位PFS的差异均无统计学意义（均P＞0．05）。结论进展期胃癌ABCB1 G2677T／A多态性与紫杉醇敏感性有一定的关系，野生型患者对紫杉醇类化疗的敏感性可能较差。

Objective To investigate the association between ABCB1 polymorphisms and chemosensitivity of paclitaxel in Chinese advanced gastric cancer （AGC） patients. Methods Clinical data and peripheral blood prior to chemotherapy of 412 AGC patients treated with first-line capecitabine plus paclitaxel （pactitaxel group, n=268） or cisplatin （cisplatin group, n=268） in Peking University Cancer Hospital from December 2008 to April 2013 were retrospectively collected. ABCB1 G2677T/A polymorphisms were determined using PCR amplification and Sanger Sequencing. Clinical response evaluation and survival analysis were performed using RECIST1.1 criteria and Kaplan-Meier curve , respectively. The associations of ABCB1 G2677T/A polymorphisms with clinical response and survival were analyzed statistically. Results The genotypes of ABCB1 were detected in all the patients and the frequency of wild type （G2677G）, single allele variants （G2677T＋G2677A）, and two allele variants （T2677T ＋T2677A ＋A2677A） was 22.8% （94/412）, 49.8% （205/412）, and 27.4% （113/412）, respectively. In paclitaxel group, the disease control rate （DCR） [89.9% （116/129）] and median progression-free survival （PFS） （190 days） of patients with single allele variants of G2677T/A were significantly higher than those of wild type patients [76.1%（51/67） and 110 days, all P〈0.05],and did not differ statistically from those with two allele variants. In cisplatin group , no significant differences were observed among patients with different genotypes of ABCB1 in terms of the DCR or PFS （all P〉0.05）. Conclusions ABCB1 G2677T/A polymorphisms are associated with chemosensitivity of paclitaxel in gastric cancer.