中国汉族人群维生素D受体基因3′区域单核苷酸多态性与前列腺癌基因危险性的关系

背景前列腺癌发病率有显著的种族差异,近来已有研究报告显示维生素D受体基因(vitaminD receptor gene,VDRG)多态性与前列腺癌的发病危险性有关,但大多集中在高发病的欧美人群.目的研究低发病的中国汉族人群VDRG单核苷酸多态性(singlenucleotide polymorphism,SNP)与前列腺癌的关系,探讨前列腺癌发病种族差异的原因.设计非随机对照研究.地点和对象329受试者(103例前列腺癌患者、112例前列腺增生及114例对照者)外周血标本,采集自北京大学第一医院.所有受试者来自北方地区的汉族人群,均知情同意.干预收集中国北方地区汉族人群103例前列腺癌患者、112例前列腺增生及114例对照者外周血标本,应用基于PCR的限制性酶切片段长度多态(restrictionfragment length polymorphism,RFLP)和变性高效液相色谱(denaturing high performanceliquid chxomatograpy,DHPLC)方法,检测VDRG 3′区域三个单核苷酸多态位点TaqI,BsmI和ApaI,并对该位点SNP分布进行分析.主要观察指标VDRG3′区域三个单核苷酸多态位点TaqI,BsmI和ApaI在病例与对照组中的分布,VDRGSNP分布与中国汉族人群前列腺癌发病危险及疾病进展的关系.结果VDRG3′区域三个SNP位点基因型和等位基因在北方地区汉族前列腺癌患者及对照中的分布频率无显著差异(P＞0.05),但TaqI和BsmI位点基因型频率分布与高发患者群相比有显著不同.器官局限性前列腺癌组(T1～T2)Tt基因型以及携带等位基因A的纯合子(AA)或杂合子(Aa)的频率明显高于对照组(P＜0.05),此外,在低分级组(Gleason＜7)携带等位基因A的纯合子(AA)或杂合子(Aa)的频率明显高于对照组(P=0.031).结论结果显示VDRG3′区域多态性在低发病的中国汉族人群与前列腺癌发病危险无关,但VDRG多态性在预测前列腺癌疾病进展有一定作用,TaqI和BsmI位点基因型频率分布与高发患者群有明显差异,可能是前列腺癌发病种族差异的原因之一.

Single nucleotide polymorphisms in the 3′region of vitamin D receptor gene and the genetic risk of prostate cancer in Chinese population

BACKGROUND: There is a significant difference in the incidence of prostate cancer among different ethnic groups. Recently, some research papers have demonstrated that there is a relatability between vitamin D receptor gene (VDRG) single nucleotide polymorphism (SNP) and prostate cancer, but most are concentrated in high-risk West population.OBJECTIVE: This study aimed at investigating any association between vitamin D receptor gene(VDRG) single nucleotide polymorphism(SNP) and prostate cancer in low-risk Chinese population and the possible reason caused by the racial differences.DESIGN: A nonrandomized controlled research was conducted.SETTING and PARTICIPANTS: The peripheral blood samples of 329persons including 103 prostate cancer cases, 112 benign prostatic hyperplasia cases and 114 controlled cases were gathered from First Hospital of Peking University. All of the people were Han people of northern China, who had known the fact and agreed.INTERVENTION: Case-control study was carried out on 103 prostate cancer patients, 112 benign prostatic hyperplasia and 114 male age-matched controls in populations of northern China. Genotyping methods for the three SNP in the 3′region of VDRG, TaqI, BsmI and Apal included polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) and denaturing high performance liquid chromatography(DHPLC).MAlN OUTCOME MEASURE: The distribution of the three SNP in the 3′region of VDRG, TaqI, BsmI and ApaI in the case group and the control group. The relationships between the distribution of VDRG SNP and the dangerous incidence and development of carcinoma of prostate in Han people of China.RESULTS: Genotype and allele frequencies of the 3′region of VDRG polymorphism showed no significant difference in prostate cancer(P ＞0.05 ). However, the distributions of genotype frequencies of BsmI and TaqI differ greatly from the high-risk populations of prostate cancer. The frequency of the AA and Aa genotype and Tt was significantly higher among prostate cancer patients with local disease(T1 -T2) as compared with control group ( P ＜ 0.05 ) . The frequency of genotype AA and Aa were statistically higher in low classified group(Gleason ＜ 7) as compared with control group ( P = 0. 031 ).