Friday, February 14, 2014

Is my BPH (benign prostatic hyperplasia) genetic?

One of the more common questions heard in urology clinic is, "Did I do something wrong to get a big prostate?"  The answer is an emphatic, "No."  We explain why below.


First, benign prostatic hyperplasia (BPH) and associated lower urinary tract symptoms (LUTS) are incredibly common:

  • Approximately 40% of 50-year old men with have histologic evidence of BPH at autopsy, this number increases to 80% for 80-year men.
  • Over the same time period, mean prostate volume increases 10-15 grams from an average baseline of 15-25 grams at age 50 to 25-40 grams at age 80.
  • The percentage of men with moderate-to-severe LUTS varies among studies and countries, but definitely increases with age.  [1]

Second, BPH is demonstrated to have a very strong heritable component.  Some of the seminal work on the inheritance of BPH is discussed next.


In 1994, Dr. Martin Sanda examined 909 consecutive patients who underwent simple prostatectomy for benign disease at the Johns Hopkins Hospital.  After investigating the families of these patients, he determined that:
  • Male relatives of men with early-onset BPH (<64 years-old) had a 66% lifetime risk of prostatectomy for BPH; compared to 17% for controls (p=0.001).
  • There was a 4-fold increase in age-specific risk of prostatectomy for BPH in men who underwent prostatectomy for BPH (p=0.003).
  • The risk of prostatectomy for BPH increased to 6-fold for brothers of affected men (p=0.0089).
  • Segregration analyses indicated a most-likely, autosomal dominant inheritance pattern. [2]
In the same year, Dr. Alan Partin examined 10,000 twins for benign prostatic disease.  He discovered:
  • The pairwise concordance for monozygotic (MZ, identical) twins was 14.7% and only 4.5% for dizygotic (DZ, fraternal) twins.  
  • The relative risk for MZ twins was therefore 3.3 (p=0.008).
  • Therefore, up to 49% of observed variance between twins could be attributed to genetic causes in covariance analyses. [3]
In 1997, Dr. Sanda defined the clinical and biological characteristics of familial BPH (which often presents with larger volume prostates at a younger age).  For men with familial BPH, mean prostate volume was 82.7 mL, while for men with sporadic BPH mean prostate volume was 55.5 mL (p<0.001). [4]

Journal of Urology, 1997; 157(3), 876-879.

Have any genes for BPH been identified?

Since the late 1990's, a number of studies have examined potential genes that cause BPH.  While a number of promising targets have been identified, no specific gene or genes have been identified.

So what should we know as patients and providers?

First, you have done nothing wrong to get a big prostate - this is incredibly common and can be normal condition, coincident with aging.
Second, more than likely, especially if you are young (<64 years-old), someone else in the family has a big prostate and symptoms like yours.
Third, we are very good at treating this disease and there are many options including observation, medical treatment and surgery if needed.

---

[1] Roehrborn, Claus G., MD.  Benign Prostatic Hyperplasia : Etiology, Pathophysiology, Epidemiology, and Natural History [Book] Campbell-Walsh Urology, chapter 91, Pages 2570-2610.e10 Copyright © 2012, 2007, 2002, 1998, 1992, 1986, 1978, 1970, 1963, 1954 by Saunders, an imprint of Elsevier Inc.

[2] Sanda MG, Beaty TH, Stutzman RE, Childs B, Walsh PC.Genetic susceptibility of benign prostatic hyperplasia.J Urol. 1994 Jul;152(1):115-9.

[3] Partin AW, Page WF, Lee BR, Sanda MG, Miller RN, Walsh PC.Concordance rates for benign prostatic disease among twins suggest hereditary influence.  Urology. 1994 Nov;44(5):646-50.

[4] Sanda MG, Doehring CB, Binkowitz B, Beaty TH, Partin AW, Hale E, Stoner E, Walsh PC.Clinical and biological characteristics of familial benign prostatic hyperplasia. J Urol. 1997 Mar;157(3):876-9. 

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