ABCC2-24C > T polymorphism is associated with the response to platinum/5-Fu-based neoadjuvant chemotherapy and better clinical outcomes in advanced gastric cancer patients

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 SNaPShot (TM) 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.National Key Technology Support Program [2014BA109B02]; Beijing Municipal Science and Technology Project [D131100005313010]; Capital Health Development Research Program [2014-1-2151]; National High Technology Research and Development Program of China (863 Program) [2014AA020603]; Beijing Municipal Science and Technology Commission [Z151100004015070]; National Technology Support Program of the Ministry of Science and Technology [2013BAI09B07]; Beijing Science and Technology Program [Z121100007512010]SCI(E)PubMedARTICLEjiafuj@hotmail.com3455449-55457