Familial aggregation of bothersome benign prostatic hyperplasia symptoms.
OBJECTIVE
To evaluate familial aggregation and the mode of inheritance of bothersome benign prostatic hyperplasia (BPH).


METHODS
During an extension of the North American Finasteride Trial, 301 of 895 patients and 158 spousal controls completed a family history questionnaire. Segregation analysis was performed to examine the mode of inheritance in first-degree relatives of the 301 probands.


RESULTS
The lifetime cumulative probability of bothersome BPH was similar in relatives of those with BPH (0.35; 95% confidence interval [CI] 0.28 to 0.44) and spousal controls (0.36; 95% CI 0.22 to 0.56), but the age of onset was significantly earlier in relatives of cases than controls (P = 0.001). Fathers of those with BPH had a significantly elevated risk of bothersome BPH (unadjusted odds ratio [OR] 2.1; 95% CI 1.2 to 3.8) and brothers had a significantly elevated risk of both bothersome BPH (OR 3.5; 95% CI 1.7 to 7.3) and transurethral resection of the prostate (OR 3.6; 95% CI 1.4 to 8.8). After adjusting for family size, the risk of bothersome BPH increased approximately twofold with each additional affected first-degree relative (0 relatives, OR 1.0; 1 relative, OR 1.7; 2 relatives, OR 4.7). Segregation analysis suggested a rare autosomal codominant allele (frequency 0.0004).


CONCLUSIONS
These findings confirm previous findings that family history and early age of onset are associated with an increased risk of BPH and that the most likely mode of inheritance is autosomal dominant or codominant. Bothersome BPH appears to have a weaker genetic component than more restrictive definitions of hereditary BPH. Thus, linkage studies are more likely to be successful if they focus on stricter definitions of hereditary BPH (eg, early onset, large volume, strong family history) rather than symptomatic or clinical BPH.
Pearson
Jay D
JD
Department of Epidemiology, Merck Research Laboratories, Merck and Co., Inc., West Point, Pennsylvania 19486-0004, USA.
Lei
Hsien-Hsien
HH
Beaty
Terri H
TH
Wiley
Kathleen E
KE
Isaacs
Sarah D
SD
Isaacs
William B
WB
Stoner
Elizabeth
E
Walsh
Patrick C
PC
D000328:Adult; D017668:Age of Onset; D000368:Aged; D016022:Case-Control Studies; D005192:Family Health; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D011470:Prostatic Hyperplasia / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics / Q000601:surgery; D012044:Regression Analysis; D016019:Survival Analysis; D020728:Transurethral Resection of Prostate / Q000706:statistics & numerical data