Understanding the Epidemiology, Natural History, and Key Pathways Involved in Prostate Cancer

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Prostate cancer accounts for about 25% of all the newly diagnosed cancers in American men and was projected to cause >28 000 deaths in 2008. Black men are disproportionately affected; their incidence rate is about 1.6 times greater than the rate for white men. As the population ages, the number of new cases per year is expected to increase by >60% and reach 300 000 by 2015. This high incidence, coupled with the protracted onset of the disease, makes PCa a particularly appropriate candidate for prevention and early intervention strategies. Potential disease precursors, particularly high-grade prostatic intraepithelial neoplasia, might help identify men at high risk of developing PCa. Dihydrotestosterone, a product converted from testosterone by 5α-reductases, plays an important role in normal prostate growth and in the development of PCa. The 5α-reductase levels, particularly type 1, appear to increase during the disease course of prostatic intraepithelial neoplasia and PCa, with greater expression occurring as the disease progresses. Therefore, the inhibition of 5α-reductase could potentially reduce the risk of PCa development, slow or prevent disease progression, and/or treat existing disease. A substantial research effort has recently focused on understanding the pathways involved in the disease's emergence and progression, particularly the 5α-reductase pathway.

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Prevalence and Incidence

Globally, prostate cancer (PCa) is highly prevalent. It is the most common noncutaneous cancer in men.1, 2 An estimated 782 600 new cases and 254 000 deaths caused by the disease occurred in 2007.3 The mortality rates for PCa have been decreasing in many developed countries (eg, the United States, the United Kingdom, and Canada), which has been attributed to improved treatment and early detection.3, 4 In contrast, PCa mortality has been increasing in some Asian countries (eg, Japan, Singapore).

Natural History

Our understanding and narrative of PCa's natural history is far from complete. This is partly because the disease is heterogeneous in both morphology and clinical behavior.15 About one third of all American men >50 years old have histologic evidence of PCa; however, most of these cases remain clinically “silent.” Multiple genetic changes appear to be necessary for clinically aggressive PCa to develop.16

How the disease develops when localized varies. Lower grade tumors (ie, highly or moderately

Current Understanding of Prostate Growth: Role of Dihydrotestosterone

Testosterone is the main circulating androgen in men.24 In the prostate and other organs, testosterone functions as a prohormone; it is converted to dihydrotestosterone (DHT) in the prostatic stromal and basal cells by 5α-reductase (5AR), an intracellular enzyme present in the prostate, skin, and liver.24, 25 In serum, the ratio of testosterone to DHT is approximately 10:1. This ratio is reversed in the prostate.26

DHT is the primary prostatic androgen and plays an essential role in prostate

Conclusions

PCa is a highly prevalent disease that imposes a significant burden on patients and the public healthcare system. The incidence of PCa is expected to increase as the U.S. population continues to age. Black men appear to be disproportionately affected; white men are significantly less likely to develop the disease; and Hispanic and Asian-American men have lower rates than white men. The natural history of PCa is far from completely understood, but our picture of the development and progression

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  • Cited by (0)

    E. D. Crawford serves as a consultant and speaker for GlaxoSmithKline, Sanofi-Aventis, and AstraZeneca and receives grant support from the National Institutes of Health and Endocare.

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