The Prostate 52:213 ^235 (2002) Hormones and Prostate Cancer: Current Perspectives and Future Directions Ann W. Hsing, 1 * Juergen K.V. Reichardt, 2 and Frank Z. Stanczyk 3 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 2 Institute for Genetic Medicine, Department of Biochemistry and Molecular Biology and Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles,California 3 Departments of Obstetrics and Gynecology and Preventive Medicine,University of Southern California, Los Angeles,California Prostate cancer is the most commonly diagnosed non-skin cancer in men in most western countries. Despite the high morbidity and mortality from prostate cancer, its etiology remains obscure. Although compelling laboratory data suggest a role for androgens in prostate carci- nogenesis, most epidemiologic data on humans are inconclusive. To provide insights and directions for future epidemiologic research on hormones and prostate cancer, this review focuses on current perspectives of serum-based studies and polymorphisms in relevant hormone-related genes. We highlight the importance of methodologic studies and investiga- tions of hormone levels in the prostatic tissue to help clarify the often-contradictory data on serologic studies. We recommend careful analysis and cautious interpretation of studies of genetic markers, including repeats and single nucleotide polymorphisms (SNPs), as false positive and negative results may arise in many current and future studies with limited statistical power and non-representative samples from the population. The review also high- lights the reasons to perform functional analyses of SNPs, a critical and often under- appreciated component of molecular epidemiologic investigations. The time is ripe for large-scale multidisciplinary investigations that incorporate molecular genetics, biochemistry, histopathology, and endocrinology into traditional epidemiologic studies. Such collaboration will lead to a deeper understanding of the etiologic pathways of prostate cancer, ultimately yielding better preventive, diagnostic, and therapeutic strategies. Prostate 52: 213–235, 2002. Published 2002 Wiley-Liss, Inc. { KEY WORDS: prostate cancer; hormones; genetic polymorphisms; epidemiology INTRODUCTION There is a striking difference in prostate cancer risk between different racial and ethnic groups, with African American men having reported incidence rates that are 40- to 60-fold higher than those reported for Asian men [1,2]. Although the reasons for this large disparity in risk are mostly unclear, population differ- ences in androgen levels have been implicated as a possible explanation. Abundant biological data suggest that androgens play an important role in the development of prostate cancer. For example, the growth and maintenance of the prostate are dependent on androgens, prostate cancer regresses after androgen ablation or anti-androgen therapy, and administration of testosterone induces prostate tumors in laboratory animals [3 –5]. However, epidemiologic studies addressing the role of andro- gens in prostate cancer have produced conflicting data [6,7], due, in part to methodologic limitations, includ- ing intra-subject and intra-laboratory variations. With *Correspondence to: Ann W. Hsing, Ph.D., National Cancer Institute, EPS-MSC 7234, 6120 Executive Blvd., Bethesda, MD 20852-7234. E-mail: hsinga@exchange.nih.gov Received 28 January 2002; Accepted 5 March 2002 DOI 10.1002/pros.10108 Published 2002 Wiley-Liss, Inc. { This article is a US Government work and, as such, is in the public domain in the United States of America.