Zhou Wu, Tao Zhihua, Wang Zhongyong, Chen Zhanguo, Shen Mo, Xu Qiyu, Xie Haixiao, Yu Zhixian, Chen Guorong
Department of Clinical Laboratory Medicine, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325005, China; Email:
Zhonghua Zhong Liu Za Zhi. 2015 Feb;37(2):107-12.
To investigate the polymorphism in the promoter region of PCA3 gene and its relationship with risk of prostate cancer (PCa).
The promoter region of PCA3 gene of the DNA of peripheral blood mononuclear cells was detected by sequence analysis in the 186 PCa and 141 BPH patients and 135 healthy control individuals. If the samples were detected with polymorphism of insection/deletion, clone sequence analysis was used with pBS-T carrier to verify it.
There were 5 polymorphisms. TAAA repeat times: 4, 5, 6, 7, 8, and 8 genotypes (TAAA 4/5, TAAA 4/6, TAAA 5/5, TAAA 5/6, TAAA 5/7, TAAA 5/8, TAAA 6/6, and TAAA 6/7) were detected in the promoter region of PCA3 gene. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. Unconditional logistic regression analysis models were used to analyze the relationship between different genotypes and cancer risks adjusted by sex and age. The type 11TAAA and ≥12TAAA was associated with higher relative risk for prostate cancer than the group ≤10TAAA [OR=1.74, 95% CI=1.06-2.87 (for type 11TAAA); OR=5.63, 95% CI=1.85-17.19 (for type ≥12TAAA)]. In the 186 PCa patients, there was 62.4% allele of PCA3 gene with AG/CA mutation found in the promoter 18-19 bp region of PCA3 gene and it had a close relation with the development of prostate cancer.
Short tandem repeats are found in the promoter region of the PCA3 gene in PCa patients, and the increase of TAAA repeat sequences highly enhance the relative risk of prostate cancer development. The occurrence of such STR might be related to the mutations in their upstream loci.
研究PCA3基因启动子区域的多态性及其与前列腺癌(PCa)风险的关系。
采用序列分析方法检测186例PCa患者、141例良性前列腺增生(BPH)患者和135例健康对照者外周血单个核细胞DNA中PCA3基因的启动子区域。若样本检测到插入/缺失多态性,则使用pBS-T载体进行克隆序列分析以验证。
共发现5种多态性。TAAA重复次数为4、5、6、7、8,并在PCA3基因启动子区域检测到8种基因型(TAAA 4/5、TAAA 4/6、TAAA 5/5、TAAA 5/6、TAAA 5/7、TAAA 5/8、TAAA 6/6和TAAA 6/7)。这8种基因型分为三组:≤10TAAA、11TAAA、≥12TAAA。采用非条件逻辑回归分析模型分析不同基因型与经性别和年龄校正后的癌症风险之间的关系。11TAAA型和≥12TAAA型与前列腺癌的相对风险高于≤10TAAA组相关[比值比(OR)=1.74,95%可信区间(CI)=1.06 - 2.87(11TAAA型);OR = 5.63,95%CI = 1.85 - 17.19(≥12TAAA型)]。在186例PCa患者中,PCA3基因启动子18 - 19 bp区域发现62.4%的PCA3基因等位基因存在AG/CA突变,且与前列腺癌的发生密切相关。
在PCa患者的PCA3基因启动子区域发现短串联重复序列,TAAA重复序列的增加显著提高了前列腺癌发生的相对风险。这种短串联重复序列的出现可能与其上游位点的突变有关。