Department of Oncology, The First Affiliated Hospital, Nanchang University, 330006, Nanchang, China.
Nanchang University School of Medicine, Nanchang University, 330006, Nanchang, China.
Wien Klin Wochenschr. 2017 Jun;129(11-12):420-426. doi: 10.1007/s00508-016-1147-x. Epub 2017 Jan 10.
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 a 28 bp sequence in 5'-UTR, denoted as 2R or 3R allele) and rs16430 (a 6 bp variation at 1494 bp in 3'-UTR, denoted as ins6 or del6 allele) and 2 single nucleotide polymorphisms (SNPs) of ABCB1gene rs2032582 in exon 21 and rs1045642 in exon 26, 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 110 Chinese AGC patients post-chemotherapy. Cox regression analysis was used to analyze the risk factors affecting patient survival. As a result, 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 rs2032582 GG were beneficial predictors of clinical treatment outcome in AGC patients, suggesting some clinical implications in chemotherapy of a Chinese population.
为了研究基因变异对接受以氟尿嘧啶（5-FU）为基础的化疗的晚期胃癌（AGC）患者生存结局的影响，我们分析了 TS 基因 rs34743033（5'-UTR 中 28bp 序列的双或三串联重复，标记为 2R 或 3R 等位基因）和 rs16430（3'-UTR 中 1494bp 处的 6bp 变异，标记为 ins6 或 del6 等位基因）以及 ABCB1 基因 rs2032582 外显子 21 和 rs1045642 外显子 26 中的 2 个单核苷酸多态性（SNP）与 5-FU 治疗后临床结局的相关性。通常，通过聚合酶链反应（PCR）和聚丙烯酰胺凝胶电泳（PAGE）检测 indels rs34743033 和 rs16430，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 SNPs rs2032582 和 rs1045642 在 110 名接受化疗后的中国 AGC 患者中进行。Cox 回归分析用于分析影响患者生存的危险因素。结果表明，rs34743033、rs1045642 和 rs2032582 与总生存（OS）显著相关（P<0.05），并且还观察到这四个多态性与无病生存（DFS）的相关性（P<0.05）。此外，我们发现 rs34743033 3R/2R、rs16430 ins6/del6、rs1045642 CC 或 CT 以及 rs2032582 GG 基因型是 AGC 患者临床治疗结局的有益预测指标，这提示在中国人中进行化疗时具有一些临床意义。
