Polymorphic markers in the 5α-reductase type II gene and the incidence of prostate cancer

Najib Lamharzi, Melissa M. Johnson, Gary Goodman, Ruth Etzioni, Noel S. Weiss, Douglas A. Dightman, Matt Barnett, Dante DiTommaso, Chu Chen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

In the prostate, the enzyme encoded by the SRD5A2 gene (5α-reductase) converts testosterone to dihydrotestosterone, a potent androgen that has been hypothesized to play a role in the genesis of prostate cancer. Several polymorphisms have been identified in the SRD5A2 gene, including a valine-to-leucine substitution (V89L) at codon 89, a variable number of TA dinucleotide repeats and a missense substitution at codon 49 resulting in an amino acid substitution of alanine with threonine (A49T). To investigate the influence of these polymorphisms on prostate cancer risk, we conducted a case-control study nested within the Beta-Carotene and Retinol Efficacy Trial. Genotypes were determined by PCR-based capillary electrophoresis using genomic DNA isolated from 300 cases and 300 controls matched on the basis of race, age at enrollment (within 5 years), enrollment study center and year of randomization. There was no association between V89L genotypes and prostate cancer risk. The age-and race-adjusted odds ratio (OR) associated with the VL and LL genotypes were 1.06 (95% confidence interval (CI) = 0.7S-1.49) and 0.99 (95% CI = 0.57-1.73), respectively, as compared to the VV genotype. The age- and race-adjusted odds ratio for men having I TA(9) or TA(18) allele was 0.98 (95% CI = 0.64-1.48) when compared to men without TA repeats. The corresponding odds ratio for men without the TA(O) alleles was 0.68 (95% CI = 0.21-2.19). The age- and race-adjusted odds ratio associated with having at least 1 T allele at codon 49 was 1.11 (95% CI = 0.58-2.11), as compared to the AA genotype. Our results do not support the hypothesis that the V89L and A49T polymorphisms in the SRD5A2 gene are related to the risk of prostate cancer, but are compatible with the suggestion from earlier studies that men who are homozygous for the TA(9) or (18) alleles and men who have the TA(9)/TA(18) genotype are at a modestly reduced risk.

Original languageEnglish (US)
Pages (from-to)480-483
Number of pages4
JournalInternational Journal of Cancer
Volume105
Issue number4
DOIs
StatePublished - Jul 1 2003

Keywords

  • Polymorphism
  • Prostate cancer, 5 alpha reductase type II
  • SRD5A2

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Polymorphic markers in the 5α-reductase type II gene and the incidence of prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Lamharzi, N., Johnson, M. M., Goodman, G., Etzioni, R., Weiss, N. S., Dightman, D. A., Barnett, M., DiTommaso, D., & Chen, C. (2003). Polymorphic markers in the 5α-reductase type II gene and the incidence of prostate cancer. International Journal of Cancer, 105(4), 480-483. https://doi.org/10.1002/ijc.11126