甲基化转移酶基因多态性与前列腺癌发病的相关性研究

目的:探讨DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)(rs16999593,rs2228611)及DNMT3B(rs2424908)基因多态性与南京地区前列腺癌发病风险及病理特征的相关性。方法:采用病例对照研究,招募前列腺癌患者155例设为病例组及155例正常男性设为对照组。采用Mass ARRAY分子量阵列技术进行基因分型技术检测3个多态性位点的基因型。采用Logistic回归模型分析各基因型与前列腺癌发生的关系及其病理参数的关系。结果:rs16999593位点的各基因型在2组中分布频率有显著性差异(P=0.041),CT基因型(OR=0.61,95%CI 0.38~0.99,P=0.043)及CT/CC(OR=0.59,95%CI 0.39~0.92,P=0.017)基因型在对照组的频率显著高于病例组。rs2424908的各基因型在两组中分布有显著性差异(P=0.025),CT基因型(OR=0.73,95%CI 0.58~0.91,P=0.007)及CT/CC基因型(OR=0.57,95%CI 0.36~0.94,P=0.023)在对照组的频率显著高于病例组。在Gleason分级7的病例组中,rs16999593CT/CC(OR=0.47,95%CI 0.28~0.85,P=0.008)及rs2424908CT/CC(OR=0.46,95%CI 0.26~0.85,P=0.009)基因型的频率均显著低于对照组。而在Gleason分级≥7的分组中上述3个多态性位点的基因型频率与对照组均无显著性差异(P均0.05)。结论:DNMT1基因rs16999593CT/CC及DNMT3B基因rs2424908CT/CC基因型与前列腺癌的低风险相关,且与Gleason低评分相关。

Polymorphisms of DNA methyltransferases and the risk of prostate cancer

Objective： To investigate the relationship between the polymorphisms of DNA methyltransferase （DNMT） and the risk and pathologic characteristics of prostate cancer （PCa） in Chinese men. Methods ： This case-control study included 155 PCa patients and 155 healthy male controls. Using Sequenom MassARRAY, we detected the genotypes of the DNMT1 polymorphisms rs16999593 and rs2228611 and the DNMT3B polymorphism rs2424908, followed by analysis of their association with the risk and pathologic characteristics of prostate cancer by logistic regression. Results： Significant differences were found in the frequency of the rs16999593 genotypes （ P = 0. 041 ） and that of the rs2424908 genotypes （ P = 0. 025 ） between the case and control groups. The frequencies of the genotypes rs16999593CT （ OR = 0.61, 95% CI 0.38 - 0.99, P = 0. 043） and rs16999593CT/CC （ OR = 0.59, 95% CI 0.39 -0.92, P = 0.017 ） were obviously higher in the control than in the case group, and so were those of rs2424908CT （OR = 0.73, 95% CI 0.58 -0.91, P =0. 007） and rs2424908CT/CC （ OR =0.57, 95% CI 0.36 -0.94, P =0. 023）. The frequencies of rs16999593CT/CC （OR = O. 47, 95% CI 0.28 - 0.85, P = 0. 008） and rs2424908CT/CC （OR = 0.46, 95% CI 0.26 - 0.85, P = 0. 009） were evidently lower in the eases with Gleason seore 〈7 than in the controls. However, none of the three polymorphisms exhibited any significant differences in the frequencies of their genotypes between the patients with Gleason score ≥7 and the healthy controls （P 〉 0.05 ）. Conclusion： The rs16999593CT/CC genotype of DNMT1 and the rs2424908CT/CC genotype of DNMT3B are associated with decreased risk of prostate cancer and lower Gleason score in C.