前列腺癌激肽释放酶3与维生素D受体基因单核苷酸多态性和环境因素与前列腺癌风险的关系

Relationship of kallikrein 3 and vitamin D receptor polymorphisms and environmental factors with prostate cancer predisposition

目的研究前列腺癌激肽释放酶3(KLK3)与维生素D受体(VDR)的单核苷酸多态性(SNPs)和环境危险因素与中国人群中前列腺癌(PCa)发病之间的关系。方法对108例PCa病例和242例正常社区对照采用TaqMan/MGB探针基因分型方法测定KLK3的SNP(rs2735839位于基因KLK2和基因KLK3之间)与VDR的SNP(rs731236位于外显子9)基因分型,同时收集人口学资料以及体质指数(BMI)、饮酒、饮茶、吸烟、体育运动等环境危险因素,通过单因素和多因素分析研究基因型及环境危险因素与PCa之间的关系。结果KLK3的SNP位点rs2735839(A/G)的基因型AA、AG、GG在PCa和对照组人群中的比例分别为13.89%、62.96%、23.15%和37.19%、44.63%、18.18%,两组间差异有统计学意义(P=0.00)。VDR的SNP位点rs731236(T/C)的基因型TT、TC、CC在PCa和对照组人群中的比例分别为88.89%、9.26%、1.85%和90.50%、9.10%、0.40%,两组间差异无统计学意义。饮茶者患PCa的危险性比不饮茶者低(OR=0.58,95%CI,0.35～0.96)。结论环境因素饮茶与PCa的发生有关,饮茶是PCa的保护因素;KLK3的SNP位点rs2735839与PCa的发生存在一定的相关性;环境因素饮茶与KLK3的SNP位点rs2735839之间存在相乘交互作用。未发现VDR的SNP位点rs731236与PCa的发生相关。

Objective To investigate the relationship of the single nucleotide polymorphisms（SNPs） of kallikrein 3（KLK3） and vitamin D receptor（VDR） and environmental factors with prostate cancer predisposition in Chinese.Methods The genotypes of KLK3（rs2735839 is located between KLK2 and KLK3） and VDR（rs731236 is located exon 9） were determined by TaqMan/MGB Probe technology in 108 prostate cancer（PCa） patients and 242 community-based normal controls.The demographic information,body mass index（BMI）,smoking,alcohol consumption,tea drinking,sport activity and other environmental factors were collected for the two groups.Univariate and multivariate logistic regression models were used to assess the relationship of genetic polymorphisms and environmental risk factors with PCa.Results The frequencies of SNPs rs2735839（A/G） for KLK3 AA,AG and GG genotypes were 13.89%,62.96% and 23.15% in PCa patients and 37.19%,44.63%,18.18% in controls,respectively,with significant difference found between the two groups（P=0.00）.The frequencies of SNPs rs731236（T/C） for VDR TT,TC and CC genotypes were 88.89%,9,26%,1.85% in PCa patients and 90.50%,9.10%,0.40% in controls,respectively,with no significant difference between the two groups.The study also showed that the risk for PCa in tea drinkers was only 0.58 fold that of non-tea drinkers（OR=0.58,95%CI,0.35-0.96）.Conclusion Our study indicates that tea drinking is associated with the development of PCa;tea drinking is a protective factor against PCa;SNPs rs2735839 of KLK3 is significantly correlated with PCa;moreover,there is a multiplicative interaction between SNPs rs2735839 of KLK3 and environment factors.SNPs rs731236 of VDR is not correlated with PCa.