DNMT1和DNMT3B基因多态性与食管癌发病风险的关联分析

Association of Polymorphisms of DNMT1 and DNMT3B with Risk of Esophageal Cancer

目的探讨DNMTl基因多态性位点（rsl6999593，rs2228611）和DNMT3B基因多态性位点（rs2424908）的基因型与食管癌及其病理参数的关联。方法采用病例对照研究，使用MassARRAY检测技术对258例食管癌患者和260例健康对照的3个多态性位点基因型分布进行分析。采用Logistic回归模型分析各基因型与食管癌发生的关系并比较不同基因型与食管癌病理参数的关系。结果DNMT1基因rs16999593位点TC基因型（OR=0．69，95％CI：0．47—1．00）和rs2228611位点GA基因型（OR=0．67，95％CI：0．46—0．98）与食管癌的低风险相关，rs16999593TC、CC基因型与食管癌分化程度相关（中分化：TCvs.TT：OR=0．53，95％CI：0．33—0．86；低分化：CCVS．1Tr：OR=2．79，95％CI：1．12—6．91），rs2228611GA基因型与高分化食管癌（GAVS．GG：OR=0．47，95％CI：0．25～0．88）和无周围淋巴结转移（GAVS．GG：OR=0．62，95％CI：0．39—0．98）有关，DNMT3B基因rs2424908CC基因型与肿瘤Ⅲ-Ⅳ分期（CCVS．Tr：OR=0．38，95％CI：0．15～0．92）及远端淋巴结转移（CCvs．TT：OR=0．18，95％CI：0．40—0．80）相关。结论本研究发现rs16999593和rs2228611位点与食管癌的发生及分化程度相关，rs2228611和rs2424908位点和淋巴结转移相关，rs2424908位点和肿瘤分期有相关性。

Objective To investigate the relationship between the polymorphisms of DNMT1 （rs16999593, rs2228611 ） and DNMT3B（rs2424908） with risk of esophageal cancer and its clinicopathological parameters. Methods A case-control study was carried out based on 258 patients with esophageal cancer and 260 health controls. The genotypes of the variants were detected by MassARRAY SNP Genotyping Assays. Logistic regression was applied to assess the association of the polymorphisms and the risk and pathologic characteristics of esophageal cancer. Results There was significant association of the rs16999593 TC genotype and the rs2228611 GA genotype of DNMT1 with decreased risk of esophageal cancer. The rs16999593 TC genotype was associated with differentiated esophageal cancer and CC genotype was associated with poorly differentiated esophageal cancer. The rs2228611 GA genotype was associated with well-differentiated esophageal cancer and lymph node metastasis. There was significant difference of rs2424908 CC genotype either in tumor Ⅲ-Ⅳ stage group or distal lymph node metastasis group with control groups in our study population. Conclusion The findings in this study suggest that rs16999593 and rs2228611 polymorphisms were associated with the risk and differentiation of esop Moreover, rs2424908 hageal cancer. Rs2836007 and rs2424908 were associated with lymph node metastasis. was associated with tumor stage