Genetic Susceptibility of Benign Prostatic Hyperplasia

Abstract

In an effort to provide new insight into the etiology of benign prostatic hyperplasia (BPH), an evaluation of genetic factors was performed. Recognizing that early age of onset is a marker for hereditary disease, we performed a case-control study of men with early onset of significant BPH. Men in the youngest quartile (less than 64 years old) with a large prostate (greater than 37 gm. resected tissue) who underwent surgery for BPH were identified as case probands from 909 consecutive prostatectomies for BPH. Control probands, selected because of the ability to distinguish treatment for benign prostate disease from treatment for malignant prostate disease, were women whose spouses underwent radical prostatectomy during the same interval. Male relatives of men with early onset of BPH had a 66% cumulative lifetime risk of prostatectomy for BPH, compared to a 17% cumulative risk among control relatives (p = 0.001). A 4-fold increase in age-specific risk of prostatectomy for BPH was present among relatives of men who had undergone prostatectomy for BPH (p = 0.0003), while brothers of these affected cases had a 6-fold increase in risk (p = 0.0089) compared to controls. To determine the likelihood that genetic factors account for this familial aggregation of BPH, segregation analysis was done. Although the small sample size prevented rigorous exclusion of nongenetic models, direct comparison of mendelian and nongenetic models showed that mendelian transmission provided the best overall explanation of the observed familial aggregation. The optimal model suggested mendelian dominant inheritance of a gene associated with early age at onset of BPH. These findings identify family history of BPH as a risk factor for clinical BPH and suggest the presence of a predisposing gene in patients with early onset BPH. Evidence of dominant mendelian transmission of this allele provides a framework for genetic studies to characterize this gene and elucidate the development of BPH in general.

Voiding dysfunction in men: pathophysiology and risk factors

“…The exact mechanism is still unknown, but there is a predisposition to younger age of onset and larger glands in patients with a family history of BPH. This is supported by the Sanda et al 28 study where a fourfold greater risk of prostatectomy in the first-degree relatives of study subjects was found. These individuals had a family history positively …”

α1a‐Adrenoceptor polymorphism: pharmacological characterization and association with benign prostatic hypertrophy

“…high level of serum cholesterol or phospholipid), geriatric disease, such as coronary heart disease, cerebrovascular disease, hypertension, diabetes mellitus to the onset of BPH (Rotkin, 1983). Also, the genetic susceptibility of BPH has been reported in recent years (Sanda et al, 1994). However, the molecular pathogenesis of this disorder is still poorly understood.…”

Lipids in the Pathogenesis of Benign Prostatic Hyperplasia: Emerging Connections

“…BPH is rarely fatal, but affects the quality of life, and if left untreated, serious lifethreatening complications may arise. Prostatic growth and development are governed by the genetic (Sanda et al, 1994), hormonal (Marker et al, 2003) and dietary factors (Bravi et al, 2006). Although, its etiology is not well understood, several theories have been proposed to explain the pathogenesis of BPH (Alberto et al, 2009;Bosch, 1991;Srinivasan et al, 1995).…”