Prostate Cancer Prevention (PDQ®): Prevention - Health Professional Information [NCI] - Risk Factors for Prostate Cancer Development
Prostate cancer incidence escalates dramatically with increasing age. Although it is a very unusual disease in men younger than 50 years, rates increase exponentially thereafter. The registration rate by age cohort in England and Wales increased from eight per thousand population in men aged 50 to 56 years to 68 per thousand in men aged 60 to 64 years; 260 per thousand in men aged 70 to 74 years, and peaked at 406 per thousand in men aged 75 to 79 years. In this same population, the death rate per thousand in 1992 in cohorts of men aged 50 to 54 years, 60 to 64 years, and 70 to 74 years was 4, 37, and 166, respectively. At all ages, incidence of prostatecancer in blacks exceeds those of whites.
Approximately 15% of men with a diagnosis of prostate cancer will be found to have a first-degree male relative (e.g., brother, father) with prostate cancer, compared with approximately 8% of the U.S. population. Approximately 9% of all prostate cancers may result from heritable susceptibility genes. Several authors have completed segregation analyses, and though a single, rare autosomal gene has been suggested to cause cancer in some of these families, the burden of evidence suggests that the inheritance is considerably more complex.[5,6,7]
The development of the prostate is dependent upon the secretion of dihydrotestosterone (DHT) by the fetal testis. Testosterone causes normal virilization of the Wolffian duct structures and internal genitalia and is acted upon by the enzyme 5-alpha-reductase (5AR) to form DHT. DHT has a 4-fold to 50-fold greater affinity for the androgen receptor than testosterone, and it is DHT that leads to normal prostatic development. Children born with abnormal 5AR (due to a change in a single base pair in exon 5 of the normal type II 5AR gene), are born with ambiguous genitalia (variously described as hypospadias with a blind-ending vagina to a small phallus) but masculinize at puberty because of the surge of testosterone production at that time. Clinical, imaging, and histologic studies of kindreds born with 5AR deficiency have demonstrated a small, pancake-appearing prostate with an undetectable prostate-specific antigen (PSA) level and no evidence of prostatic epithelium. Long-term follow-up demonstrates that neither benign prostatic hyperplasia (BPH) nor prostate cancer develop.
Other evidence suggesting that the degree of cumulative exposure of the prostate to androgens is related to an increased risk of prostate cancer includes the following:
Neither BPH nor prostate cancer have been reported in men castrated prior to puberty.
Androgen deprivation in almost all forms leads to involution of the prostate, a fall in PSA levels, apoptosis of prostate cancer and epithelial cells, and a clinical response in prostate cancer patients.[10,11]
The results of two large-scale chemoprevention trials using 5AR inhibitors (finasteride and dutasteride) demonstrate that intraprostatic androgens modulate prostate cancer risk. In both studies, reductions in overall prostate cancer risk were identified although with increased risk of high-grade disease.[12,13]