This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cicek, M. S. Articles by Witte, J. S. Search for Related Content PubMed PubMed Citation Articles by Cicek, M. S. Articles by Witte, J. S.

Role of Androgen Metabolism Genes CYP1B1, PSA/KLK3, and CYP11 in Prostate Cancer Risk and Aggressiveness

¹ Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic Lerner School of Medicine, Cleveland, Ohio and ² Department of Epidemiology and Biostatistics, University of California, San Francisco, California

Requests for reprints: John S. Witte, Department of Epidemiology and Biostatistics, University of California, San Francisco, 500 Parnassus Avenue, MU-420 West San Francisco, CA 94143-0560. Phone: 415-476-1374; Fax: 415-476-6014. E-mail: jwitte{at}itsa.ucsf.edu

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 CYP11 [(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.

This article has been cited by other articles:

				J. Beuten, J. A.L. Gelfond, J. L. Franke, K. S. Weldon, A. C. Crandall, T. L. Johnson-Pais, I. M. Thompson, and R. J. Leach Single and Multigenic Analysis of the Association between Variants in 12 Steroid Hormone Metabolism Genes and Risk of Prostate Cancer Cancer Epidemiol. Biomarkers Prev., June 1, 2009; 18(6): 1869 - 1880. [Abstract] [Full Text] [PDF]

				J. Beuten, J. A.L. Gelfond, J. J. Byrne, I. Balic, A. C. Crandall, T. L. Johnson-Pais, I. M. Thompson, D. K. Price, and R. J. Leach CYP1B1 variants are associated with prostate cancer in non-Hispanic and Hispanic Caucasians Carcinogenesis, September 1, 2008; 29(9): 1751 - 1757. [Abstract] [Full Text] [PDF]

				A. Hamada, T. Sissung, D. K. Price, R. Danesi, C. H. Chau, N. Sharifi, D. Venzon, K. Maeda, K. Nagao, A. Sparreboom, et al. Effect of SLCO1B3 Haplotype on Testosterone Transport and Clinical Outcome in Caucasian Patients with Androgen-Independent Prostatic Cancer Clin. Cancer Res., June 1, 2008; 14(11): 3312 - 3318. [Abstract] [Full Text] [PDF]

				B. A. Rybicki, C. Neslund-Dudas, C. H. Bock, A. Rundle, A. T. Savera, J. J. Yang, N. L. Nock, and D. Tang Polycyclic Aromatic Hydrocarbon-DNA Adducts in Prostate and Biochemical Recurrence after Prostatectomy Clin. Cancer Res., February 1, 2008; 14(3): 750 - 757. [Abstract] [Full Text] [PDF]

				O. Cussenot, A. R. Azzouzi, N. Nicolaiew, G. Fromont, P. Mangin, L. Cormier, G. Fournier, A. Valeri, S. Larre, F. Thibault, et al. Combination of Polymorphisms From Genes Related to Estrogen Metabolism and Risk of Prostate Cancers: The Hidden Face of Estrogens J. Clin. Oncol., August 20, 2007; 25(24): 3596 - 3602. [Abstract] [Full Text] [PDF]

				N. L. Nock, D. Tang, A. Rundle, C. Neslund-Dudas, A. T. Savera, C. H. Bock, K. G. Monaghan, A. Koprowski, N. Mitrache, J. J. Yang, et al. Associations between Smoking, Polymorphisms in Polycyclic Aromatic Hydrocarbon (PAH) Metabolism and Conjugation Genes and PAH-DNA Adducts in Prostate Tumors Differ by Race Cancer Epidemiol. Biomarkers Prev., June 1, 2007; 16(6): 1236 - 1245. [Abstract] [Full Text] [PDF]

				J. Lai, M.-A. Kedda, K. Hinze, R. L.G. Smith, J. Yaxley, A. B. Spurdle, C.P. Morris, J. Harris, and J. A. Clements PSA/KLK3 AREI promoter polymorphism alters androgen receptor binding and is associated with prostate cancer susceptibility Carcinogenesis, May 1, 2007; 28(5): 1032 - 1039. [Abstract] [Full Text] [PDF]

				N. L. Nock, M. S. Cicek, L. Li, X. Liu, B. A. Rybicki, A. Moreira, S. J. Plummer, G. Casey, and J. S. Witte Polymorphisms in estrogen bioactivation, detoxification and oxidative DNA base excision repair genes and prostate cancer risk Carcinogenesis, September 1, 2006; 27(9): 1842 - 1848. [Abstract] [Full Text] [PDF]

				N. L. Nock, X. Liu, M. S. Cicek, L. Li, F. Macarie, B. A. Rybicki, S. J. Plummer, G. T. MacLennan, G. Casey, and J. S. Witte Polymorphisms in polycyclic aromatic hydrocarbon metabolism and conjugation genes, interactions with smoking and prostate cancer risk. Cancer Epidemiol. Biomarkers Prev., April 1, 2006; 15(4): 756 - 761. [Abstract] [Full Text] [PDF]