Prostate cancer is the most common non-cutaneous malignancy in American men.10 It is also primarily a disease of men beyond their reproductive years, thereby severely limiting the evolutionary selective process against cancer.11 Observational data suggest that environment plays an important role in determining the risk of prostate cancer. First, there is tremendous species specificity of prostate cancer, with a significant incidence of spontaneous prostate cancer observed only in humans and dogs.11 None of man's closest primate relatives are susceptible to carcinoma of the prostate. Second, there is tissue specificity for cancer among men's reproductive organs. Despite sharing similar genetics and microenvironments, the human vas defer-ens and seminal vesicle rarely undergo malignant transformation. In addition, ethnic and geographical variations exist in the incidence of prostate cancer. Compared to the USA, the risk of prostate cancer is as much as tenfold less in Asian countries, a tendency that is lost upon immigration and adoption of a Western diet.11'12 Lastly, there is a high incidence of early pathological changes in the prostate epithelium of both American and Asian men, suggesting that differences in molecular promotion and not initiation explain the observed variations in incidence and mortality.11,13 Taken together, these data support the influence of the environment and epigenetic events on the clinical progression of prostate cancer.
The prostate originates from solid epithelial outgrowths that emerge from the endodermal urogenital sinus below the developing bladder at approximately 10 weeks gestation. The prostatic buds grow into the adjacent mesenchyme, lengthen to form ducts, arborize and canalize.14 By 13 weeks approximately 70 primary ducts exist, which exhibit secretory cyto-differentiation.15 Further embryonic growth involves ductal proliferation and the establishment of prostate zonal anatomy. Considerable cellular heterogeneity exists across the prostatic ductal epithelium (Fig. 10.1). Signals derived from the developing prostatic stroma are believed to control the rate and fate of proliferating prostate epithelial cells.16
The human prostate is known to undergo several growth phases: fetal growth, followed by limited regression after birth and growth cessation, then ultimately prostatic regrowth accompanying the androgen surge of puberty until adulthood at which time the process stops17 (Fig. 10.2). In man and dog, prostatic growth is reiterated during aging as part of benign or neoplastic proliferative processes. This has led McNeal to theorize a 'reawakening' of embryonic growth within the prostate.18 Studies of prostatic cellular proliferation demonstrate that prostate epithelial growth occurs early in a man's life, peaking in men 30-40 years old when prostate doubling times are 4-5 years. However, clinical benign prostatic hyperplasia (BPH) and prostate cancer are much more common during the seventh and eighth decades of life, when prostate epithelial growth is minimal and doubling times are significantly longer.17,19 These data suggest that for chemopreventative strategies to be maximally effective, they must be applied to men much younger than those typically at risk for developing prostate cancer.
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