Elsevier

Urology

Volume 57, Issue 1, January 2001, Pages 199-204
Urology

Basic science
V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression

https://doi.org/10.1016/S0090-4295(00)00928-6Get rights and content

Abstract

Objectives. The valine (V) to leucine (L) polymorphism of the SRD5A2 gene is associated with 5-alpha reductase-2 activity; patients with the V allele have high activity and patients with the L allele have low activity. We examined whether this polymorphism predicts the presence of prostate cancer in 320 men without cancer who underwent biopsy and cancer progression in 318 men who underwent radical prostatectomy.

Methods. The effect of the SRD5A2 gene in predicting the presence of prostate cancer was examined using logistic regression analysis, controlling for established risk factors. The effect of the SRD5A2 gene in predicting prostate cancer progression was examined using a nested, matched, case-control design. Most of the participants were white.

Results. Of the 320 men, 158 (49.4%) were found on biopsy to have prostate cancer. The overall distribution of the V/V, V/L, and L/L genotypes was 47.5%, 42.5%, and 10.0%, respectively. The adjusted odds ratio for having prostate cancer for patients with at least one V allele was 2.53 compared with patients with the L/L genotype (P = 0.03). Of the 318 patients with cancer, 80 had biochemically detected recurrence and 238 had no evidence of recurrence. The odds ratio for progression for patients with at least one V allele was 3.32 (95% confidence interval 1.67 to 6.62, P = 0.0006) compared with patients with the L/L genotype.

Conclusions. Men who have the V allele of the SRD5A2 gene have a twofold increase in the risk of prostate cancer development and an additional twofold increase in the risk of progression compared with men with the L/L genotype.

Section snippets

Study subjects

To examine the effects of the SRD5A2 polymorphism on prostate cancer risk and progression, we used two independent study samples because of the different requirements for the control population. The first study determined the probability of the presence of prostate cancer by the SRD5A2 polymorphism by comparing patients with and without prostate cancer. The second study determined the probability of prostate cancer progression by the SRD5A2 polymorphism by comparing patients with established

Prostate cancer risk

Of the 320 men, 158 patients (49.4%) were found at biopsy to have prostate cancer (patients). Of the 162 men with no evidence of cancer (controls), 81 (50%) had normal prostatic tissue, 35 (22%) had evidence of inflammation, benign prostatic hyperplasia, or cellular atypia, and 46 (28%) had prostatic intraepithelial neoplasia. The mean age of the patients and controls was 66.6 and 65.5 years, respectively (P = 0.22). The mean PSA level of the patients and controls was 14.6 and 10.7 ng/mL,

Comment

This study is the first that relates a host susceptibility factor to both prostate cancer risk and progression on the basis of biologic observations relating 5-alpha reductase-2 activity to this polymorphism. Febbo et al.22 did not find a positive association between prostate cancer risk and the SRD5A2 V89L polymorphism. However, all patients with prostate cancer were selected, including patients who presented with metastases and those who did not undergo PSA screening, in sharp contrast to our

Conclusions

The results of these two studies demonstrate that, after controlling for established factors for prostate cancer risk and progression, patients who have the V allele of the SRD5A2 gene have a twofold increase in the risk of prostate cancer development and an additional twofold increase in the risk of progression compared with patients with the L/L genotype.

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    This study was supported by grant 009112 from the National Cancer Institute of Canada. Dr. Nam was supported by a research fellowship from the Surgical Scientist Program, Department of Surgery, University of Toronto, Toronto, Canada.

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