Influence of TS and ABCB1gene polymorphisms on survival outcomes of 5‑FU-based chemotherapy in aChinese population of advanced gastric cancer patients.

Abstract

To investigate the impacts of gene variations on survival outcomes of advanced gastric cancer (AGC) patients treated with 5‑fluorouracil (5-FU)-based chemotherapy, we analyzed the associations of 2 indels of the TS gene rs34743033 (double or triple tandem repeats of a28 bp sequence in 5'-UTR, denoted as 2R or 3R allele) and rs16430 (a6 bp variation at 1494 bp in 3'-UTR, denoted as ins6 or del6allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon21 and rs1045642 in exon26, with clinical outcomes after 5‑FU treatment. Generally, indels rs34743033 and rs16430 were genotyped by PCR and polyacrylamide gel electrophoresis assay and SNPs rs2032582 and rs1045642 were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay in 110Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As aresult, rs34743033, rs1045642 and rs2032582 were shown to be significantly associated with overall survival (P< 0.05), and associations between the four polymorphisms with disease-free survival were also observed (P< 0.05). Moreover, we found that genotypes rs34743033 3R/2R, rs16430 ins6/del6, rs1045642 CC or CT, and rs2032582GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of aChinese population.