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Epidemiology and Prevention |
Yale University School of Medicine, New Haven, Connecticut 06510 [J. M. J., R. P.], and Departments of Biostatistics and Epidemiology [J. M. J., A. H. W., S. M., T. R. R.], Urology [S. B. M., K. V. A., A. J. W.], and Pathology and Laboratory Medicine [J. T.], University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6021
The enzyme product of SRD5A2, 5
-reductase type II, is
responsible for converting testosterone to the more metabolically
active dihydrotestosterone. Therefore, SRD5A2 may be
involved in the development or growth of prostate tumors. To examine
the effects of allelic variants in the gene SRD5A2 on
the presentation of prostate tumors, we studied a sample, primarily
Caucasian, of 265 men with incident prostate cancer who were
treated by radical prostatectomy. We assessed the relationship of the
A49T and V89L polymorphisms at
SRD5A2 with clinical and pathological tumor
characteristics of these patients. We found no association of
V89L genotypes with any of the characteristics studied.
The presence of the A49T variant was associated with a
greater frequency of extracapsular disease [odds ratio (OR), 3.16;
95% confidence interval (CI), 1.03–9.68] and a higher pathological
tumor-lymph node-metastasis (pTNM) stage (OR, 3.11; 95% CI,
1.01–9.65). In addition, the A49T variant was
overrepresented in two poor prognostic groups, which have been
correlated with reduced rates of biochemical disease-free survival. One
group included men with at least two of the following poor prognostic
variables: (a) stage T3 tumor; (b) PSA
level >10; and/or (c) Gleason score, 7–10 (OR, 3.46;
95% CI, 1.04–11.49). The second group included men with positive
margins and high Gleason score (OR, 6.28; 95% CI, 1.05–37.73).
Our results suggest that the A49T mutation may influence
the pathological characteristics of prostate cancers and, thus, may
affect the prognosis of these patients.
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