Androgen Metabolism and Prostate Cancer: Establishing a Model of Genetic SusceptibilityRoss R.K. · Coetzee G.A. · Pearce C.L. · Reichardt J.K.V. · Bretsky P. · Kolonel L.N. · Henderson B.E. · Lander E. · Altshuler D. · Daley G.
Departments of aPreventive Medicine, bUrology; cInstitute for Genetic Medicine, USC School of Medicine, Los Angeles, Calif.; dEpidemiology Program, University of Hawaii at Manoa Cancer Research Center, Honolulu, Hawaii; eWhitehead Institute/MIT, Center for Genome Research, fDepartment of Biology, MIT, and gDepartment of Medicine, Massachusetts General Hospital, Boston, Mass., USA
The prostate is an androgen-regulated organ, which has led to longstanding interest in the role of androgens in prostate carcinogenesis. Although evidence of a hormonal etiology for prostate cancer is strong, it is almost entirely circumstantial. Much of the problem in proving a causal relationship relates to the continued difficulties in reliably measuring human tissue-specific exposure to endogenous steroid hormones. The international and racial-ethnic variations in prostate cancer incidence, combined with the effects of migration on risk patterns, have suggested that genetic factors play a central role in determining prostate cancer risk. We are developing a polygenic model of prostate carcinogenesis, focused around a series of genes involved in androgen biosynthesis, transport and metabolism. We have begun to develop this model by utilizing sequence variants to study how polymorphic markers in two genes (SRD5A2 and AR) are related to prostate cancer risk within and between racial-ethnic groups. We are now collaborating with the Whitehead Institute/MIT, Center for Genome Research, to screen for single nucleotide polymorphisms in additional genes relevant to the androgen pathway and prostate cell growth. The model when fully developed can potentially provide a basis for targeting populations for screening interventions and for implementing primary preventive strategies.
Brian E. Henderson, MD
USC/Norris Comprehensive Cancer Center
1441 Eastlake Ave., #4425
Los Angeles, CA 90033-0800 (USA)
Tel. +1 323 865 0419, Fax +1 323 865 0427, E-Mail firstname.lastname@example.org
Number of Print Pages : 7
Number of Figures : 1, Number of Tables : 1, Number of References : 38
Official Organ of the European Association of Urology
Vol. 35, No. 5-6, Year 1999 (Cover Date: May-June 1999)
Journal Editor: C.C. Schulman, Brussels
ISSN: 0302–2838 (Print), eISSN: 1421–993X (Online)
For additional information: http://www.karger.ch/journals/eur