DNMT1基因多态性对胃癌患者术后生存时间的影响

Influence of single nucleotide polymorphisms of DNMT1 gene in survival of patients with gastric cancer after operation

目的：探讨中国北方汉族人群DNA甲基转移酶1（DNMT1）基因单核苷酸多态性（SNPs）与胃癌患者术后生存时间的关系,阐明DNMT1基因多态性与胃癌预后的关联性。方法：选取447例经胃癌根治术治疗的胃癌患者纳入研究队列。利用TaqMan SNP技术检测DNMT1的5个SNPs位点（rs16999593、rs10420321、rs2288349、rs2228611和rs2228612）的基因型分布。对447例胃癌术后患者进行长期跟踪随访,采用KaplanMeier方法计算胃癌患者术后的生存时间并绘制生存曲线;以Log-rank检验分析不同基因型患者生存时间的差异。利用单因素和多因素Cox回归模型计算风险比（HR）及95%可信区间（CI）。结果：与DNMT1基因rs2228611GG基因型比较,携带GA/AA基因型的患者预后更好,生存时间更长（52.5和42.9个月,Log-rank P=0.006）。在多因素回归调整了混杂因素后,与rs2228611GG基因型比较,携带GA/AA基因型患者的死亡风险下降了32%（HR：0.68,95%CI：0.50～0.92,P=0.013）,表明rs2228611位点基因多态是胃癌患者术后生存的独立影响因素。未发现其余4个位点的基因多态性与胃癌患者预后有关联性。结论：中国北方汉族人群DNMT1rs2228611GA/AA基因多态性胃癌患者的生存时间延长,DNMT1基因多态性可作为预测胃癌预后的分子标志。

Objective To investigate the association between the single nucleotide polymorphisms（SNPs）of DNA methyltransferase 1（DNMT1）gene and the survival of the patients with gastric cancer after operation in the Han population from North China,and to clarify the association between the polymorphisms of DNMT1 gene and prognosis of gastric cancer.Methods A total of 447 gastric cancer patients treated with total gastrectomy were selected into the cohort study.The distribution of genotypic frequencies of five SNPs sites（rs16999593,rs10420321,rs2288349,rs2228611 and rs2228612）of DNMT1 were detected by TaqMan assay.447 cases of gastric cancer patients were followed up.Kaplan-Meier method was used to calculate the survival and draw the survival curves,and Log-rank test was used to compare the differences of overall survival（OS）between the patients with different genotypes.The hazardratio（HR）and 95% confidence interval（CI）were estimated by univariate and multivariate Cox regression analysis.Results Compared with the patients carried GG genotype at the rs2228611 site,the patients with GA/AA genotypes had better prognosis and Longer survival time（52.5months vs 42.9months,Log-rank P=0.006）.After adjusting the confounding factors,the patients carried rs2228611GA/AA genotypes had a decreased death risk than the patients with GG genotype（HR 0.68,95% CI：0.50-0.92,P=0.013）,suggesting that the polymorphisms of rs2228611 site was an independent influencing factor of prognosis of the patients with gastric cancer after operation.There was no association between the polymorphisms of other sites and the prognosis of gastric cancer.Conclusion The polymorphisms of DNMT1rs2228611GA/AA genotypes can prolong the survival time of the patients with gastric cancer.The polymorphism of DNMT1 could be used as a biomarker to predict the prognosis of gastric cancer.