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中国人群中DNA修复基因多态性与胃癌化疗反应及预后的相关性

Association of DNA repair gene polymorphisms with response to chemotherapy and prognosis of gastric cancer in a Chinese population.

作者信息

Li Junkai, Zuo Xiaoyan, Lv Xiaoyan, Kong Fanjun, Xu Wen, Yang Shujuan

机构信息

Department of Oncology, The 456th Hospital of PAL, Jinan, 250031, China,

出版信息

Tumour Biol. 2014 Aug;35(8):7569-74. doi: 10.1007/s13277-014-1959-0. Epub 2014 May 4.

Abstract

We conducted a study to investigate the role of excision repair cross-complimentary group 1 gene (ERCC1)-xeroderma pigmentosum complementation group F (XPF) gene polymorphisms in response to chemotherapy and clinical outcome of gastric patients. Three SNPs in ERCC1 (rs11615, rs3212986, and rs2298881) and two SNPs in XPF (rs2276465 and rs6498486) were extracted using Tiangen DNA kit (Tiangen Biotech, Beijing, China) according to the manufacturer's instructions. The median follow-up time was 36.4 months, and ranged from 2-60 months. During the follow-up period, 112 patients died from gastric cancer. Individuals carrying ERCC1 rs11615 AA and XPF rs6498486 CC genotypes were associated with poorer response to chemotherapy when compared with wild-type genotype, with the ORs (95 % CI) of 0.48 (0.25-0.94) and 0.38 (0.14-1.00). In the Cox proportional hazards model, individuals carrying ERCC1 rs11615 GA and AA genotype had 1.91 and 2.66 risk of death when compared with those carrying GG genotype. Patients carrying the XPF rs6498486 AC and CC genotype were associate with 2.17 and 4.91-fold risk of death when compared with wild-type genotype. In conclusion, we found that ERCC1 rs11615 and XPF rs2276465 may substantially contribute to the future design of individualized cancer treatment in gastric cancer patients.

摘要

我们开展了一项研究,以调查切除修复交叉互补组1基因(ERCC1)-着色性干皮病互补组F(XPF)基因多态性在胃癌患者化疗反应及临床结局中的作用。按照制造商的说明,使用天根DNA试剂盒(天根生化科技(北京)有限公司)提取ERCC1基因的3个单核苷酸多态性(SNP,rs11615、rs3212986和rs2298881)以及XPF基因的2个SNP(rs2276465和rs6498486)。中位随访时间为36.4个月,范围为2至60个月。随访期间,112例患者死于胃癌。与野生型基因型相比,携带ERCC1 rs11615 AA和XPF rs6498486 CC基因型的个体对化疗的反应较差,其比值比(95%可信区间)分别为0.48(0.25 - 0.94)和0.38(0.14 - 1.00)。在Cox比例风险模型中,与携带GG基因型的个体相比,携带ERCC1 rs11615 GA和AA基因型的个体死亡风险分别为1.91倍和2.66倍。与野生型基因型相比,携带XPF rs6498486 AC和CC基因型的患者死亡风险分别为2.17倍和4.91倍。总之,我们发现ERCC1 rs11615和XPF rs2276465可能对未来胃癌患者个体化癌症治疗方案的设计有重要意义。

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