title: Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness.
abstract: Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: -158A/G, -4643G/A, and -5412C/T), and CYP11alpha [(tttta)(n) repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism-or their haplotypes-and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA -158G/-158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% CI, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Lerner School of Medicine, Ohio, USA.
authors.forename: Mine S
authors.initials: MS
authors.lastname: Cicek
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Graham
authors.initials: G
authors.lastname: Casey
authors.forename: John S
authors.initials: JS
authors.lastname: Witte
mesh_terms: D000368:Aged; D000728:Androgens / Q000378:metabolism; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics*; D065633:Cytochrome P-450 CYP1B1; D018450:Disease Progression; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010375:Pedigree; D016133:Polymerase Chain Reaction; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D012307:Risk Factors
chemical_list: D000728:Androgens; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; D065633:Cytochrome P-450 CYP1B1; D002786:Cholesterol Side-Chain Cleavage Enzyme; D017430:Prostate-Specific Antigen