Genetic variants in the CYP24A1 gene are associated with prostate cancer risk and aggressiveness in a Korean study population.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
1] CHA Bundang Medical Center, Department of Urology, CHA University, Seongnam, Korea [2] CHA Cancer Research Center, CHA University, Seoul, Korea.
J J
JJ
Oh
Department of Urology, Seoul National University Bundang Hospital, Seongnam-si, Korea.
S-S
SS
Byun
Department of Urology, Seoul National University Bundang Hospital, Seongnam-si, Korea.
S E
SE
Lee
Department of Urology, Seoul National University Bundang Hospital, Seongnam-si, Korea.
S K
SK
Hong
Department of Urology, Seoul National University Bundang Hospital, Seongnam-si, Korea.
C W
CW
Jeong
Choi Won Suk Urology Clinic, Youngin, Korea.
W S
WS
Choi
Department of Biochemistry and Molecular Biology, Pennsylvania State University, University Park, PA, USA.
D
D
Kim
1] Advanced Urogenital Disease Research Center, Chung-Ang University College of Medicine, Seoul, Korea [2] Research Institute for Translational System Biomics, Chung-Ang University College of Medicine, Seoul, Korea.
H J
HJ
Kim
1] Advanced Urogenital Disease Research Center, Chung-Ang University College of Medicine, Seoul, Korea [2] Research Institute for Translational System Biomics, Chung-Ang University College of Medicine, Seoul, Korea [3] Department of Urology, Chung-Ang University College of Medicine, Seoul, Korea.
S C
SC
Myung
D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007610:Kallikreins / Q000235:genetics; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D012306:Risk; D012307:Risk Factors; D065668:Vitamin D3 24-Hydroxylase / Q000235:genetics*
C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen