TY - JOUR
T1 - Association of Prostate Cancer Risk and Aggressiveness to Androgen Pathway Genes
T2 - SRD5A2, CYP17, and the AR
AU - Cicek, Mine S.
AU - Conti, David V.
AU - Curran, Anthony
AU - Neville, Phillippa J.
AU - Paris, Pamela L.
AU - Casey, Graham
AU - Witte, John S.
PY - 2004/4/1
Y1 - 2004/4/1
N2 - 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.
AB - 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.
KW - Androgens
KW - Cancer
KW - Candidate genes
KW - Case-control study
KW - Prostatic neoplasms
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U2 - 10.1002/pros.10358
DO - 10.1002/pros.10358
M3 - Article
C2 - 14991867
AN - SCOPUS:1642284253
SN - 0270-4137
VL - 59
SP - 69
EP - 76
JO - Prostate
JF - Prostate
IS - 1
ER -