Basic scienceV89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression☆
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.