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Polymorphisms in genes involved in sex hormone metabolism may increase risk of benign prostatic hyperplasia
Author(s) -
Roberts Rosebud O.,
Bergstralh Erik J.,
Farmer Sara A.,
Jacobson Debra J.,
Hebbring Scott J.,
Cunningham Julie M.,
Thibodeau Stephen N.,
Lieber Michael M.,
Jacobsen Steven J.
Publication year - 2005
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.20362
Subject(s) - medicine , hyperplasia , genotype , hazard ratio , prostate , endocrinology , lower urinary tract symptoms , prostate cancer , prostate specific antigen , sex hormone binding globulin , urinary system , confidence interval , gastroenterology , hormone , androgen , biology , gene , cancer , genetics
Background This study investigates associations between polymorphisms in genes involved in sex hormone metabolism and measures of benign prostatic hyperplasia (BPH). Methods Community‐dwelling Caucasian men (n = 510, median age 60 years in 2000) from the Olmsted County, MN, participated in a longitudinal study of BPH. From 1990 through 2000, urologic measures of BPH were assessed biennially from lower urinary tract symptom severity, peak flow rates, prostate volume, serum prostate specific antigen (PSA) level, acute urinary retention, and treatment for BPH. Men were genotyped for polymorphisms in genes involved in sex hormone metabolism. Results With the wildtype genotype as reference, men with HSD3B1 (c.1100 A/C) heterozygous genotype (hazard ratio (HR) = 0.7, 95% confidence intervals (CI) = 0.6, 0.9) were at decreased risk of an enlarged prostate and men with CYP19 ( TTTA ) n genotype homozygous for ≥175 TTTA repeats (HR = 1.5, 95% CI = 1.1, 2.1), and CYP19 (c.1531 C/T) homozygous T variant (HR = 1.6, 95% CI = 1.1, 2.2) were at increased risk of an enlarged prostate. The homozygous A variant of the PSA gene (g.‐252 G/A), was associated with treatment for BPH (HR = 2.3, 95% CI = 1.2, 4.4). In multivariate analyses, the homozygous variant genotypes of AKR1C3 (c.15 G/A and c.90 G/A) were associated with a decreased risk of an enlarged prostate (HR = 0.56, 95% CI = 0.35, 0.90 and HR = 0.57, 95% CI = 0.33, 0.98). Conclusions Polymorphisms in HSD3B1 , CYP19 , AKR1C3 genes may be associated with an enlarged prostate in older men. These data provide insights into genes that should be examined further for their potential role in the pathogenesis of BPH. © 2005 Wiley‐Liss, Inc.