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Association of prostate cancer risk and aggressiveness to androgen pathway genes: SRD5A2 , CYP17 , and the AR
Author(s) -
Cicek Mine S.,
Conti David V.,
Curran Anthony,
Neville Phillippa J.,
Paris Pamela L.,
Casey Graham,
Witte John S.
Publication year - 2003
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.10358
Subject(s) - prostate cancer , medicine , oncology , prostate , testosterone (patch) , disease , cancer , androgen , incidence (geometry) , risk factor , gynecology , hormone , physics , optics
BACKGROUND The prostate is an androgen‐regulated organ and polymorphisms in genes involved in testosterone synthesis, in particular, SRD5A2 (A49T and V89L variants ) , CYP17 (MspAI variant ) , and the AR (CAG, GGC repeats), represent candidate risk factors for prostate cancer incidence and aggressiveness. METHODS We evaluated the relationship between these five polymorphisms and prostate cancer risk in a family‐based case‐control study (N = 920). Cases were diagnosed at major medical institutions in Cleveland Ohio, and Detroit Michigan, and their unaffected brothers were used as controls. Associations were investigated with regard to prostate cancer risk, and clinical characteristics at diagnosis (i.e., tumor stage/grade, age, family history). RESULTS The SRD5A2 V89L variant was associated with an increased risk of prostate cancer (OR = 1.56, P = 0.02). This association was driven primarily by men diagnosed at an earlier age (OR = 2.35, P = 0.001), or with more aggressive disease (OR = 1.63, P = 0.06). None of the other variants exhibited noteworthy associations with disease. CONCLUSIONS These findings suggest that the SRD5A2 V89L variant may influence risk of developing prostate cancer, especially among men with a younger age of diagnosis or more aggressive disease. © 2003 Wiley‐Liss, Inc.