Polymorphisms in the androgen receptor and type II 5 alpha-reductase genes and prostate cancer prognosis.
BACKGROUND
Cytosine-adenine-guanine repeat length of the androgen receptor gene and the A49T and V89L polymorphisms of the 5 alpha-reductase (SRD5A2) gene have been associated with prostate cancer.


METHODS
We investigated the relationship of the three genetic polymorphisms to tumor grade among 211 men who had undergone radical prostatectomy. Subjects had prostate cancer <3 cm(3) with a percentage of cancer represented by Gleason grade 4 or 5 (% Gleason grade 4/5) of either > or = 20% or < or = 5%. We also examined the association between those genetic markers and prostate specific antigen (PSA) failure among 112 subjects with > or = 20% Gleason grade 4/5.


RESULTS
In cross-sectional analysis, none of the polymorphisms was a significant predictor of % Gleason grade 4/5. In longitudinal analysis, the LL genotype at the V89L site was associated with statistically significant four- to sixfold increase in PSA failure risk after adjustment for clinicopathologic variables.


CONCLUSIONS
We observed poorer prognosis among men with the LL genotype at codon 89 of the SRD5A2 gene. Lack of consistency between studies must be resolved before clinical utility of this marker is established.
Shibata
Atsuko
A
Department of Health Research and Policy, Stanford University School of Medicine, Stanford, California 94305-5405, USA. ashibata@stanford.edu
Garcia
Maria Isabel
MI
Cheng
Iona
I
Stamey
Thomas A
TA
McNeal
John E
JE
Brooks
James D
JD
Henderson
Stavonnie
S
Yemoto
Cheryl E
CE
Peehl
Donna M
DM
D014408:Biomarkers, Tumor; D042944:Cholestenone 5 alpha-Reductase; D003062:Codon; D003430:Cross-Sectional Studies; D004273:DNA, Neoplasm / Q000235:genetics*; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D010088:Oxidoreductases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000097:blood; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D014408:Biomarkers, Tumor; D003062:Codon; D004273:DNA, Neoplasm; D005819:Genetic Markers; D010088:Oxidoreductases; D042944:Cholestenone 5 alpha-Reductase; D017430:Prostate-Specific Antigen