北方汉族人群易感基因多态性与前列腺癌危险关系及对发病种族差异的分析  

Genetic risk factors of prostate cancer in Han nationality population in Northern China and a preliminary study of the reason of racial difference in prevalence of prostate cancer

作　　者：刘建河[1] 李鸿伟[1] 佟明[1] 李鸣[1] 那彦群[1] 

机构地区：[1]北京大学第一医院泌尿外科北京大学泌尿外科研究所,100034

出　　处：《中华医学杂志》2004年第5期364-368,共5页National Medical Journal of China

基　　金：国家自然科学基金资助项目 (3 0 0 70 75 5 )

摘　　要：目的　研究低发病的中国北方汉族人群雄激素受体 (AR)基因、5α 还原酶 (SRD5A2 )基因和维生素D受体 (VDR)基因多态性与前列腺癌发病危险性的关系 ,与高发病人群基因多态性的分布频率进行比较 ,探讨前列腺癌发病种族差异的原因。方法　应用病例对照研究的方法 ,对 112例前列腺癌患者和190名健康对照者 (均来自中国北方汉族人群 )外周血提取的DNA样本 ,应用限制性酶切片段长度多态性和变性高效液相色谱的方法 ,对VDR、AR、SRD5A2基因的不同多态位点进行检测 ,并对不同多态位点基因型分布频率与高发病人群进行比较研究。结果　在中国北方汉族人群 ,前列腺癌易感基因AR基因CAG微卫星多态与前列腺癌的发病危险明显相关 ,AR基因CAG重复次数小于 2 2的频率在病例组明显高于对照组 (P <0 0 5 )。VDR和SRD5A2基因型频率在病例、对照两组间无明显差异 (P >0 0 5 )。与西方高发病人群相比 ,VDR基因BsmⅠ和TaqⅠ,SRD5A2基因V89L ,AR基因CAG微卫星多态位点的基因型频率分布存在显著差异。结论　中国北方汉族人群AR基因CAG多态与前列腺癌发病危险相关 ,可作为前列腺癌的基因危险因素 ,来确定高危人群。不同种族人群前列腺癌易感基因的不同多态位点基因型频率分布的差异 ,可能是前列腺癌发病种族差异的原因之一。Objective To investigate the genetic polymorphisms of the three major susceptibility genes, AR, VDR, and SRD5A2 genes, in the Han nationality population in Northern China with a low risk of prostate cancer (Pca) and the relationship of these polymorphisms to the susceptibility to Pca, and to discuss the possible reason causing racial difference of prevalence of PCa. Methods Restriction fragment length polymorphism (RFLP) technique and denaturing high-performance liquid chromatography (DHPLC) were used to detect the polymorphic sites in the DNAs from the peripheral blood samples of 116 patients with PCa and 190 normal male controls, all of Han nationality in Northern China. The distribution frequencies of different polymorphic sites were compared with those of the populations with high risk of prostate cancer. Results The frequencies of SRD5A2 and VDR genotypes were not significantly different between the Pca patients and the controls (P>0.05). The frequency of CAG repeat <22 was significantly higher in the Pca group than in the control group (P<0.05). Statistical analyses of the AR genotype prevalence showed significant differences between the PCa patients and the controls (P<0.05). The frequencies of AR, VDR, and SRD5A2 genotypes showed significant difference between the Han population in Northern China and the high-PCa risk populations in Western countries. The frequency of CAG≥22 was 80.4% in the Han people in Northern China, significantly higher than that in the US Caucasians (52.1%) and Afro-Americans (25%, both P<0.001). Conclusion There is a significant association between the AR gene CAG polymorphisms and PCa in the Han nationality population in Northern China. The distributions of the genotypes of AR, SRD5A2 and VDR gene are different among different ethnic population, which may be one of the reasons causing the racial difference in prostate cancer risk.

关 键 词：华北地区 汉族人群 易感基因 基因多态性 前列腺癌 高效液相色谱 

分 类 号：R737.25[医药卫生—肿瘤]