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SRD5A2 and HSD3B2 polymorphisms are associated with prostate cancer risk and aggressiveness
Author(s) -
NeslundDudas Christine,
Bock Cathryn H.,
Monaghan Kristin,
Nock Nora L.,
Yang James J.,
Rundle Andrew,
Tang Deliang,
Rybicki Benjamin A.
Publication year - 2007
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20625
Subject(s) - prostate cancer , medicine , allele , prostate , endocrinology , allele frequency , genotype , dihydrotestosterone , oncology , biology , genetics , cancer , androgen , gene , hormone
BACKGROUND Dihydrotestosterone (DHT) is believed to play an important role in prostate carcinogenesis. Five alpha reductase type II ( SRD5A2 ) and 3 beta‐hydroxysteroid dehydrogenase type II ( HSD3B2 ) are responsible for the biosynthesis and degradation of DHT in the prostate. Two polymorphisms, a valine (V) for leucine (L) substitution at the 89 codon of the SRD5A2 gene and a (TG)n,(TA)n,(CA)n repeat polymorphism within the third intron of the HSD3B2 gene were evaluated with regard to prostate cancer risk. METHODS Blood samples were collected for 637 prostate cancer cases and 244 age and race frequency matched controls. In analysis, the SRD5A2 VL and LL genotypes were combined into one group and the HSD3B2 repeat polymorphism was dichotomized into short (<283) and long (≥283) alleles. RESULTS The SRD5A2 V89L polymorphism was not independently associated with prostate cancer risk. Carriage of at least one HSD3B2 intron 3 intron 3 short allele was associated with a significant increased risk for prostate cancer among all subjects (OR = 2.07, 95% CI = 1.08–3.95, P = 0.03) and Caucasians (OR = 2.80, CI = 2.80–7.43, P = 0.04), but not in African Americans (OR = 1.50, CI = 0.62–3.60, P = 0.37). Stratified analyses revealed that most of the prostate cancer risk associated with the intron 3 HSD3B2 short allele was confined to the SRD5A2 89L variant subgroup and indicated that in combination these polymorphisms may be associated with increased risk of aggressive (Gleason >7) disease (Gleason >7). CONCLUSIONS In Caucasians, the HSD3B2 (TG)n,(TA)n,(CA)n intron 3 length polymorphism is associated with both prostate cancer risk and aggressiveness and the SRD5A2 V89L polymorphism may modify the risk conferred by this polymorphism. Prostate 67: 1654–1663, 2007. © 2007 Wiley‐Liss, Inc.