Androgen-metabolic genes in prostate cancer predisposition and progression

Abstract

Prostate cancer is the most common nonskin cancer and the second leading cause of cancer deaths among men in most Western countries, including the US and Australia. Despite its high morbidity and mortality, the etiology of prostate cancer remains elusive. Longstanding clinical and compelling laboratory data suggest a role for androgens in prostate carcinogenesis. This chapter reviews the status of research on hormones, particularly androgens, and prostate cancer and focuses first on hormone-related genetic loci in constitutional (germline) DNA. This set of loci has been investigated in a number of studies to date that will undoubtedly expand further. These data provide insights into susceptibility for prostate cancer. This review next explores the emerging field of somatic mutations in tumor ("somatic") DNA in androgen-metabolic genes, especially the androgen receptor and the type II steroid 5α-reductase. Integration of these forthcoming data with those on susceptibility may provide novel insights into the etiology and progression of prostate cancer. These lines of investigation may lead to the presymptomatic identification of high-risk individuals for active disease prevention, diagnostic improvements in affected men and personalized treatment. Current and future data on individual markers and genes should be integrated into a comprehensive, pathway-based picture that includes constitutional DNA (for prostate cancer susceptibility) and tumor DNA (for disease progression). These efforts may lead to a comprehensive genetically based risk and progression assessment algorithm. © 2009 Springer-Verlag New York.