Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11α in prostate cancer risk and aggressiveness

Mine S. Cicek, Xin Liu, Graham Casey, John S. Witte

Research output: Contribution to journalArticle

47 Scopus citations

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 CYP11α [(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.

Original languageEnglish (US)
Pages (from-to)2173-2177
Number of pages5
JournalCancer Epidemiology Biomarkers and Prevention
Volume14
Issue number9
DOIs
StatePublished - Sep 1 2005

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

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