Li Ziyu, Xing Xiaofang, Shan Fei, Li Shuangxi, Li Zhongwu, Xiao Aitang, Xing Zhaodong, Xue Kan, Li Zhemin, Hu Ying, Jia Yongning, Miao Rulin, Zhang Lianhai, Bu Zhaode, Wu Aiwen, Ji Jiafu
Department of Gastrointestinal Surgery, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Department of Gastrointestinal Translational Research, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China.
Oncotarget. 2016 Aug 23;7(34):55449-55457. doi: 10.18632/oncotarget.10961.
Several studies have evaluated the efficacy of neoadjuvant treatment using oxaliplatin and fluoropyrimidines in advanced gastric cancer (GC). However, preoperative biomarkers predictive of clinical outcome remain lacking. We examined polymorphisms in the MTHFR, DPYD, UMPS, ABCB1, ABCC2, GSTP1, ERCC1, and XRCC1 genes to evaluate their usefulness as pharmacogenetic markers in a cohort of 103 GC patients treated with preoperative chemotherapy. DNA was extracted from peripheral blood cells, and the genotypes were analyzed using a SNaPShotTM assay, polymerase chain reaction amplification, and sequencing. The ABCC2-24C > T (rs717620) genotype was associated with pathologic response to neoadjuvant chemotherapy. Patients with the TT and TC genotypes responded to neoadjuvant chemotherapy 3.80 times more often than those with the CC genotype (95% CI: 1.27-11.32). Patients with the CC genotype also had poorer outcomes than those with other genotypes. Thus, ABCC2-24C > T polymorphism may help to predict the response to preoperative chemotherapy in GC patients.
多项研究评估了奥沙利铂和氟嘧啶新辅助治疗晚期胃癌（GC）的疗效。然而，仍缺乏预测临床结局的术前生物标志物。我们检测了103例接受术前化疗的GC患者队列中MTHFR、DPYD、UMPS、ABCB1、ABCC2、GSTP1、ERCC1和XRCC1基因的多态性，以评估其作为药物遗传学标志物的实用性。从外周血细胞中提取DNA，并使用SNaPShotTM分析、聚合酶链反应扩增和测序对基因型进行分析。ABCC2-24C>T（rs717620）基因型与新辅助化疗的病理反应相关。TT和TC基因型患者对新辅助化疗的反应频率是CC基因型患者的3.80倍（95%CI：1.27-11.32）。CC基因型患者的预后也比其他基因型患者差。因此，ABCC2-24C>T多态性可能有助于预测GC患者对术前化疗的反应。
