Epidemiologic Reviews Copyright © 2001 by the Johns Hopkins University Bloomberg School of Public Health All rights reserved Vol. 23, No. 1 Printed in U.S.A. Potential Agents for Prostate Cancer Chemoprevention Otis W. Brawley 1 and Shakia T. Barnes 2 INTRODUCTION Studies of the incidence and mortality of prostate cancer in various countries suggest that changeable environmental elements are important in its etiology (1). Several studies have demonstrated that migration from areas of low risk to areas of high risk is associated with an increased risk of prostate cancer in the migrants compared with men remain- ing in the low-risk country of origin (1). In migration stud- ies done before the prostate-specific antigen screening era, Japanese migrants to the United States were shown to have a marked increase in prostate cancer, although the rates of Japanese-Americans remain less than those of whites (2). Prostate cancer incidence rates are very low in eastern Europe and Russia, but Polish migrants to the United States acquire higher rates upon migration. While population studies do suggest that there may be a genetic component to some prostate cancers, there are likely to be numerous environmental components to prostate carcinogenesis and prostate cancer prevention (3). Nutritional factors in defined populations, especially in those with high animal fat and high dairy intake, have been correlated with a greater risk of disease (4). It has been suggested that populations with higher circulating levels of androgens and insulin-like growth factors tend to have higher risk of prostate cancer (5, 6). Both circulating androgens and insulin-like growth factor levels are associ- ated with diet (7, 8). In at least one case-control study with age-adjusted analyses, there were positive associations of prostate cancer (all stages combined) risk with total energy intake as well as intake of total fat (saturated and monoun- saturated) (9). There are also correlations between popula- tions with higher consumption of selenium and vitamin E, fructose/fruits, and tomatoes and lower risk of prostate cancer (10). These observations combined with an improved understanding of the biology of prostate cancer Received for publication December 5, 2000, and accepted for publication May 25, 2001. Abbreviations: NSAIDs, non-steroidal anti-inflammatory drugs; SELECT, Selenium and Vitamin E Comparison Trial. 1 Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA. 2 Office of the Director, National Cancer Institute, Bethesda, MD. Reprint requests to Dr. Otis W. Brawley, Winship Cancer Institute, Emory University School of Medicine, Emory Clinic Building B, Suite B4100,1365-B Clifton Road, Atlanta, GA 30322 (e-mail: otis_brawley@ emory.org). provide numerous leads in the effort to find workable prostate cancer chemoprevention (11). CONCEPT OF CHEMOPREVENTION Chemoprevention is the administration of agents to pre- vent induction and inhibit or delay progression of cancers. Important to chemoprevention is the fact that carcinogene- sis is a process over time involving cellular growth and division. Inhibition of or slowing this process can poten- tially prevent cancers from becoming clinically significant (12). While chemoprevention of cancer is a relatively new concept, the chemoprevention of other diseases is common although often not called chemoprevention. The prevention of heart disease with lipid lowering drugs is widely accepted, as is the prevention of tooth decay with flouride or prevention of osteoporosis in postmenopausal women with estrogen (13). These are all examples of chemopre- vention of disease. Chemoprevention involves the treatment of healthy subjects. As such, chemopreventive agents must have low toxicity in order to be clinically useful (14-16). Because their purpose is to keep something from occurring, defin- itive clinical studies to demonstrate their efficacy are necessarily randomized, blinded, long-term, and large in size. It has been suggested that androgen is an important pro- moter of prostate cancer. It has long been appreciated that prostate cancer is an androgen-driven illness. Removal of androgenic stimulation has been used to treat metastatic disease for some time (17). Populations with impaired androgen metabolism, such as congenital 5oc-reductase defi- ciency, do not develop prostate cancer. There is also the sug- gestion that populations with higher circulating levels of androgen or higher sensitivity to androgens are at greater risk of prostate cancer (18, 19). Oxidative stress has been proposed as a promoter of the process of carcinogenesis. Oxidation can lead to genetic mutations which can, in turn, lead to malignancy. Antioxidants have been suggested as potential preventative agents for a number of cancers (4). DIET AND PROSTATE CANCER Dietary intervention is not classically considered chemoprevention, but it could be very important in the prevention of prostate cancer. Some dietary elements may cause prostate cancer, whereas elements in other diets may 168 Downloaded from https://academic.oup.com/epirev/article-abstract/23/1/168/434766 by guest on 08 February 2019