ERCC1基因多态性与胃癌发生发展的关系

  目的  本研究拟探讨切除修复互补交叉基因1(ERCC1)3个单核苷多态性(SNPs)与胃癌发生发展的关系。  方法  选取2007年1月至2009年12月福建地区组织学确诊的452例胃癌患者和469例健康体检人群, 利用基质辅助激光解吸电离飞行时间质谱(MALDI-TOF-MS)方法进行rs11615 T > C、rs2298881 C > A和rs3212930 T > C、3个位点多态性检测, 以评估ERCC1不同基因型与胃癌发病风险和病理特征的关系。  结果  rs11615 T > C位点携带C等位基因的个体患胃癌的风险较野生纯合基因型降低一半(OR=0.49;95%CI: 0.52~0.47;P=0.01), 但是罹患弥漫型胃癌的风险上升1.68倍, 预后更差(OR=1.68;95%CI: 0.76~0.61;P=0.048)。单体型分析显示, 基于这3个位点的单体型C-C-C降低了体患胃癌的风险(OR=0.729;95%CI: 0.531~1.001;P=0.0499), 而单体型T-C-T则增加了胃癌患病的风险(OR=1.321;95%CI: 1.063~1.641;P=0.0118)。  结论  ERCC1基因rs11615 T > C位点多态性与胃癌发生发展密切相关, 携带该基因2种不同单体型的个体在胃癌患病风险上存在差异。 

Association of ERCC1 Gene Single Nucleotide Polymorphisms with Gastric Cancer Development and Progression

  Objective  To explore the correlations of single nucleotide polymorphisms (SNPs) in the excision repair cross-complementation group 1 (ERCC1) gene with the development and progression of gastric carcinoma (GC).  Methods  A total of 452 gastric carcinoma patients in Fujian province and 469 cancer-free controls in a population frequency-matched by age and sex were included in this study. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry was used to determine the genotype of three SNPs, including rs11615 T > C, rs2298881 C > A, and rs3212930 T > C. The correlations of these polymorphisms with the susceptibility to gastric cancer were evaluated.  Results  Compared with the TT genotype, rs11615 T > C with the C allele lowered the risk of GC (OR = 0.49, 95 % CI: 0.52~0.47, P = 0.01), indicating some protective effect on GC risk. However, rs11615 T > C with the C allele caused a higher risk for diffused GC, signifying poor prognosis (OR = 1.68, 95 % CI = 0.76~0.61, P = 0.048). SHEsis software analysis revealed that the haplotype C-C-C based on rs11615 T > C, rs2298881 C > A, and rs3212930 T > C polymorphisms lowered the risk of GC, with OR = 0.729 (95 % CI: 0.531~1.001, P = 0.049 9). In contrast, the haplotype T-C-T had a dangerous effect on GC, with OR = 1.321 (95 % CI: 1.063~1.641, P = 0.011 8).  Conclusion  The rs11615 SNP of the ERCC1 gene contributes to the susceptibility to GC. The interactions among rs11615 T > C, rs2298881, and rs3212930 T > C had synergistic effects on GC.