V89L polymorphism of type-2, 5-alpha reductase enzyme gene predicts prostate cancer presence and progression.
OBJECTIVE
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.
Nam
R K
RK
Division of Urology, Princess Margaret Hospital, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Toi
A
A
Vesprini
D
D
Ho
M
M
Chu
W
W
Harvie
S
S
Sweet
J
J
Trachtenberg
J
J
Jewett
M A
MA
Narod
S A
SA
D000368:Aged; D000483:Alleles; D042944:Cholestenone 5 alpha-Reductase; D018450:Disease Progression; D005500:Follow-Up Studies; D005819:Genetic Markers; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D009364:Neoplasm Recurrence, Local / Q000201:enzymology; D016017:Odds Ratio; D010088:Oxidoreductases / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics; D014633:Valine / Q000235:genetics
D005819:Genetic Markers; D009363:Neoplasm Proteins; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; D007930:Leucine; D014633:Valine