Oh J J, Byun S-S, Lee S E, Hong S K, Jeong C W, Choi W S, Kim D, Kim H J, Myung S C
1] CHA Bundang Medical Center, Department of Urology, CHA University, Seongnam, Korea [2] CHA Cancer Research Center, CHA University, Seoul, Korea.
Department of Urology, Seoul National University Bundang Hospital, Seongnam-si, Korea.
Prostate Cancer Prostatic Dis. 2014 Jun;17(2):149-56. doi: 10.1038/pcan.2014.1. Epub 2014 Feb 4.
Vitamin D-deactivating enzyme CYP24A1 had controversial effects on prostate cancer risk; the genetic study also showed the controversial results. Therefore, we identified the relationships between polymorphisms in CYP24A1 and prostate cancer in a Korean cohort.
We evaluated the association between 21 single-nucleotide polymorphisms (SNPs) in the CYP24A1 and prostate cancer in Korean men (272 prostate cancers and 173 controls). BPH patients with high PSA or abnormal digital rectal examination who underwent negative prostate biopsy were enrolled in the control group. Twenty-one SNPs in the CYP24A1 were selected from the International HapMap database and the NCBI database with calculation of minor allele frequency and linkage disequilibrium, preferably including the SNPs that were nonsynonymous and located within exons. We also investigated the association between 21 SNPs in the CYP24A1 gene and known clinical characteristics, such as the PSA level, clinical stage, pathological stage and Gleason score.
The statistical analysis suggested that five CYP24A1 sequence variants (rs2248461-odds ratio (OR): 0.63, rs2248359-OR: 0.65, rs6022999-OR: 0.65, rs2585428-OR: 0.46, rs4809959-OR: 0.52) had a significant association with prostate cancer risk after multiple comparisons by a method of false discovery rate. Logistic analyses of the CYP24A1 polymorphisms with several prostate cancer-related factors showed that several SNPs were significant: four SNPs to PSA level, three to clinical stage, two to pathological stage and two SNPs to the Gleason score.
The results of this study suggest that some CYP24A1 gene polymorphisms might be associated with the risk of prostate cancer in Korean men. Five CYP24A1 sequence variants showed the significance to predict prostate cancer, and several SNPs of CYP24A1 gene had an important finding to predict prostate cancer-related factors. However, these results should be validated in future large-scale studies.
维生素D失活酶CYP24A1对前列腺癌风险的影响存在争议；基因研究也显示出相互矛盾的结果。因此，我们在一个韩国队列中确定了CYP24A1基因多态性与前列腺癌之间的关系。
我们评估了韩国男性（272例前列腺癌患者和173例对照）中CYP24A1基因的21个单核苷酸多态性（SNP）与前列腺癌之间的关联。前列腺活检阴性的高PSA或直肠指检异常的良性前列腺增生患者被纳入对照组。从国际人类基因组单体型图数据库和NCBI数据库中选择CYP24A1基因的21个SNP，并计算次要等位基因频率和连锁不平衡，优先选择非同义且位于外显子内的SNP。我们还研究了CYP24A1基因的21个SNP与已知临床特征之间的关联，如PSA水平、临床分期、病理分期和Gleason评分。
统计分析表明，通过错误发现率方法进行多重比较后，5个CYP24A1序列变异（rs2248461，优势比（OR）：0.63；rs2248359，OR：0.65；rs6022999，OR：0.65；rs2585428，OR：0.46；rs4809959，OR：0.52）与前列腺癌风险显著相关。对CYP24A1基因多态性与几种前列腺癌相关因素进行的逻辑分析表明，几个SNP具有显著性：4个SNP与PSA水平相关，3个与临床分期相关，2个与病理分期相关，2个SNP与Gleason评分相关。
本研究结果表明，某些CYP24A1基因多态性可能与韩国男性前列腺癌风险相关。5个CYP24A1序列变异对预测前列腺癌具有显著性，CYP24A1基因的几个SNP对预测前列腺癌相关因素有重要发现。然而，这些结果应在未来的大规模研究中得到验证。
