REVIEW of Clinical Studies Showing Lycopene
and Reduced Risk of PROSTATE CANCER

#92 Book World Cancer Research Fund/American Institute for Cancer Research Food Nutrition and Prevention of Cancer: a global perspective. American Institute for Cancer Research, Washington DC, 1997. No Abstract.

#151 Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC Channing Laboratory, Department of Medicine, Harvard Medical School, Boston, MA 02115, USA. Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl Cancer Inst 1995 Dec 6;87(23):1767-1776 BACKGROUND: Several human studies have observed a direct association between retinol (vitamin A) intake and risk of prostate cancer; other studies have found either an inverse association or no association of intake of beta-carotene (the major provitamin A) with risk of prostate cancer. Data regarding carotenoids other than beta-carotene in relation to prostate cancer risk are sparse. PURPOSE: We concluded a prospective cohort study to examine the relationship between the intake of various carotenoids, retinol, fruits, and vegetables and the risk of prostate cancer. METHODS: Using responses to a validated, semiquantitative food-frequency questionnaire mailed to participants in the Health Professionals Follow-up Study in 1986, we assessed dietary intake for a 1-year period for a cohort of 47,894 eligible subjects initially free of diagnosed cancer. Follow-up questionnaires were sent to the entire cohort in 1988, 1990, and 1992. We calculated the relative risk (RR) for each of the upper categories of intake of a specific food or nutrient by dividing the incidence rate of prostate cancer among men in each of these categories by the rate among men in the lowest intake level. All P values resulted from two-sided tests. RESULTS: Between 1986 and 1992, 812 new cases of prostate cancer, including 773 non-stage A1 cases, were documented. Intakes of the carotenoids beta-carotene, alpha-carotene, lutein, and beta-cryptoxanthin were not associated with risk of non-stage A1 prostate cancer; only lycopene intake was related to lower risk (age- and energy-adjusted RR = 0.79; 95% confidence interval [CI] = 0.64-0.99 for high versus low quintile of intake; P for trend = .04). Of 46 vegetables and fruits or related products, four were significantly associated with lower prostate cancer risk; of the four--tomato sauce (P for trend = .001), tomatoes (P for trend = .03), and pizza (P for trend = .05), but not strawberries--were primary sources of lycopene. Combined intake of tomatoes, tomato sauce, tomato juice, and pizza (which accounted for 82% of lycopene intake) was inversely associated with risk of prostate cancer (multivariate RR = 0.65; 95% CI = 0.44-0.95, for consumption frequency greater than 10 versus less than 1.5 servings per week; P for trend = .01) and advanced (stages C and D) prostate cancers (multivariate RR = 0.47; 95% CI = 0.22-1.00; P for trend = .03). No consistent association was observed for dietary retinol and risk of prostate cancer. CONCLUSIONS: These findings suggest that intake of lycopene or other compounds in tomatoes may reduce prostate cancer risk, but other measured carotenoids are unrelated to risk. IMPLICATIONS: Our findings support recommendations to increase vegetable and fruit consumption to reduce cancer incidence but suggest that tomato-based foods may be especially beneficial regarding prostate cancer risk.

#152 Mills PK, Beeson WL, Phillips RL, Fraser GE Department of Preventive Medicine, Loma Linda University School of Medicine, CA 92350. Cohort study of diet, lifestyle, and prostate cancer in Adventist men. Cancer 1989 Aug 1;64(3):598-604 Dietary and lifestyle characteristics were evaluated in relation to subsequent prostatic cancer risk in a cohort of approximately 14,000 Seventh-day Adventist men who completed a detailed lifestyle questionnaire in 1976 and who were monitored for cancer incidence until the end of 1982. During the 6-year follow-up period, 180 histologically confirmed prostatic cancers were detected among some 78,000 man-years of follow-up. Increasing educational attainment was associated with significantly decreased risk of prostate cancer in this study; age at first marriage was also inversely associated with risk, although this was not significant. There was no relationship between body mass index (as measured by Quetelet's Index) and risk. A history of prostate "trouble" was associated with a 60% increase in risk which was highly significant. Although there were suggestive relationships between increasing animal product consumption and increased risk, these results did not persist after accounting for the influence of fruit and vegetable consumption. Nor was exposure to the vegetarian lifestyle during the childhood years associated with alterations in subsequent risk. However, increasing consumption of beans, lentils and peas, tomatoes, raisin, dates, and other dried fruit were all associated with significantly decreased prostate cancer risk.

#153 Hsing AW, Comstock GW, Abbey H, Polk BF Department of Epidemiology, School of Hygiene and Public Health, Johns Hopkins University, Baltimore, MD. Serologic precursors of cancer. Retinol, carotenoids, and tocopherol and risk of prostate cancer. J Natl Cancer Inst 1990 Jun 6;82(11):941-946 We investigated the associations of serum retinol, the carotenoids beta-carotene and lycopene, and tocopherol (vitamin E) with the risk of prostate cancer in a nested case-control study. For the study, serum obtained in 1974 from 25,802 persons in Washington County, MD, was used. Serum levels of the nutrients in 103 men who developed prostate cancer during the subsequent 13 years were compared with levels in 103 control subjects matched for age and race. Although no significant associations were observed with beta-carotene, lycopene, or tocopherol, the data suggested an inverse relationship between serum retinol and risk of prostate cancer. We analyzed data on the distribution of serum retinol by quartiles, using the lowest quartile as the reference value. Odds ratios were 0.67, 0.39, and 0.40 for the second, third, and highest quartiles, respectively.

#154 Nomura AM, Stemmermann GN, Lee J, Craft NE Japan-Hawaii Cancer Study, Kuakini Medical Center, Honolulu, Hawaii 96817, USA. Serum micronutrients and prostate cancer in Japanese Americans in Hawaii. Cancer Epidemiol Biomarkers Prev 1997 Jul;6(7):487-491 Numerous dietary studies and several serum micronutrient studies have produced equivocal results on the relation of vitamins A and E to prostate cancer risk. To evaluate this association further, we conducted a nested case-control study in a cohort of 6860 Japanese-American men examined from 1971 to 1975. At the time of examination, a single blood specimen was obtained, and the serum was frozen. After a surveillance period of more than 20 years, 142 tissue-confirmed incident cases of prostate cancer were identified. Their stored sera and those of 142 matched controls were measured by high-performance liquid chromatography for the following: total carotenoids, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha-carotene, beta-carotene, total retinoids, retinol, total tocopherols, alpha-tocopherol, delta-tocopherol, and gamma-tocopherol. Odds ratios for prostate cancer, based on quartiles of serum micronutrient levels, were determined using conditional logistic regression analysis. The odds ratio for the highest quartiles were 1.8 (95% confidence interval, 0.9-3.9) for beta-cryptoxanthin, 1.6 (0.8-3.5) for beta-carotene, 0.8 (0.4-1.5) for retinol, and 0.7 (0.3-1.5) for gamma-tocopherol, but none of the differences was statistically significant. For the other micronutrients, the results were also unremarkable. The findings of this study indicate that none of the micronutrients is strongly associated with prostate cancer risk.

#169 Olson KB, Pienta KJ Vitamins A and E: further clues for prostate cancer prevention. J Natl Cancer Inst 1998 Mar 18;90(6):414-415 No Abstract Comment on: J Natl Cancer Inst 1998 Mar 18;90(6):440-6

#176 Giovannucci E, Rimm EB, Stampfer MJ, Colditz GA, Willett WC Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA 02115, USA. Diabetes mellitus and risk of prostate cancer (United States). Cancer Causes Control 1998 Jan;9(1):3-9 A lower risk of prostate cancer among diabetics has been suggested by several but not all studies. However, the studies have not always accounted for time since diagnosis of diabetes mellitus, or have not examined confounding factors such as diet and diagnostic bias. We thus examined this relationship in the Health Professionals Follow-Up Study from 1986 and 1994, in which 1,369 new cases of non-stage A1 prostate cancer were documented in 47,781 men. A prior history of a diagnosis of diabetes (mostly adult-onset) was associated with a reduced risk of prostate cancer (multivariate relative risk [RR] = 0.75; 95 percent confidence interval [CI] = 0.59-0.95) controlling for age, body mass index (wt/ht2) at age 21, and, in 1986, race, vasectomy, and intakes of total energy, total fat, calcium, fructose, and lycopene. After excluding the first year of follow-up after the diagnosis of diabetes, the RR was 0.63 (CI = 0.54-0.89). Prostate cancer was not reduced in the first five years after diagnosis (RR = 1.24, CI = 0.87-1.77), but was lower in the next five years (RR = 0.66, CI = 0.39-1.10) and lowest after 10 years (RR = 0.54, CI = 0.37-0.78); P-value for trend across time = 0.004. Similar associations were noted for advanced cases. Detection bias was unlikely to account for our findings. The basis of this relationship is unclear but may reflect hormonal changes related to diabetes, perhaps low testosterone levels.

#210 Rentzepis MJ; Newmark H; Lipkin M; Fair WR; Tomassi M; Huryk R; Heston WDW Lycopene does not inhibit the growth of subcutaneously implanted LNCaP tumor cells in nude mice: Implications for chemoprevention. JOURNAL OF UROLOGY 1998, Vol 159, Iss 5, pp 13-13 NO ABSTRACT

#223 Giovannucci E, Clinton SK Harvard Medical School, Channing Laboratory, Boston, Massachusetts 02115, USA. Tomatoes, lycopene, and prostate cancer. Proc Soc Exp Biol Med 1998 Jun;218(2):129-139 NO ABSTRACT

#236 Yoshizawa K, Willett WC, Morris SJ, Stampfer MJ, Spiegelman D, Rimm EB, Giovannucci E Department of Nutrition, Harvard School of Public Health, Boston, MA, USA. Study of prediagnostic selenium level in toenails and the risk of advanced prostate cancer. J Natl Cancer Inst 1998 Aug 19;90(16):1219-1224 BACKGROUND: In a recent randomized intervention trial, the risk of prostate cancer for men receiving a daily supplement of 200 microg selenium was one third of that for men receiving placebo. By use of a nested case-control design within a prospective study, i.e., the Health Professionals Follow-Up Study, we investigated the association between risk of prostate cancer and prediagnostic level of selenium in toenails, a measure of long-term selenium intake. METHODS: In 1986, 51,529 male health professionals aged 40-75 years responded to a mailed questionnaire to form the prospective study. In 1987, 33,737 cohort members provided toenail clippings. In 1988, 1990, 1992, and 1994, follow-up questionnaires were mailed. From 1989 through 1994, 181 new cases of advanced prostate cancer were reported. Case and control subjects were matched by age, smoking status, and month of toenail return. Selenium levels were determined by neutron activation. All P values are two-sided. RESULTS: The selenium level in toenails varied substantially among men, with quintile medians ranging from 0.66 to 1.14 microg/g for control subjects. When matched case-control data were analyzed, higher selenium levels were associated with a reduced risk of advanced prostate cancer (odds ratio [OR] for comparison of highest to lowest quintile = 0.49; 95% confidence interval [CI] = 0.25-0.96; P for trend = .11). After additionally controlling for family history of prostate cancer, body mass index, calcium intake, lycopene intake, saturated fat intake, vasectomy, and geographical region, the OR was 0.35 (95% CI = 0.16-0.78; P for trend = .03). CONCLUSIONS: Our results support earlier findings that higher selenium intakes may reduce the risk of prostate cancer. Further prospective studies and randomized trials of this relationship should be conducted. Comment in: J Natl Cancer Inst 1998 Aug 19;90(16):1184-5

#248 Gann PH, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, Stampfer MJ Department of Preventive Medicine, Northwestern University Medical School, Chicago, Illinois 60611, USA. pgann@nwu.edu Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 1999 Mar 15;59(6):1225-30 Dietary consumption of the carotenoid lycopene (mostly from tomato products) has been associated with a lower risk of prostate cancer. Evidence relating other carotenoids, tocopherols, and retinol to prostate cancer risk has been equivocal. This prospective study was designed to examine the relationship between plasma concentrations of several major antioxidants and risk of prostate cancer. We conducted a nested case-control study using plasma samples obtained in 1982 from healthy men enrolled in the Physicians' Health Study, a randomized, placebo-controlled trial of aspirin and beta-carotene. Subjects included 578 men who developed prostate cancer within 13 years of follow-up and 1294 age- and smoking status-matched controls. We quantified the five major plasma carotenoid peaks (alpha- and beta-carotene, beta-cryptoxanthin, lutein, and lycopene) plus alpha- and gamma-tocopherol and retinol using high-performance liquid chromatography. Results for plasma beta-carotene are reported separately. Odds ratios (ORs), 95% confidence intervals (Cls), and Ps for trend were calculated for each quintile of plasma antioxidant using logistic regression models that allowed for adjustment of potential confounders and estimation of effect modification by assignment to either active beta-carotene or placebo in the trial. Lycopene was the only antioxidant found at significantly lower mean levels in cases than in matched controls (P = 0.04 for all cases). The ORs for all prostate cancers declined slightly with increasing quintile of plasma lycopene (5th quintile OR = 0.75, 95% CI = 0.54-1.06; P, trend = 0.12); there was a stronger inverse association for aggressive prostate cancers (5th quintile OR = 0.56, 95% CI = 0.34-0.91; P, trend = 0.05). In the placebo group, plasma lycopene was very strongly related to lower prostate cancer risk (5th quintile OR = 0.40; P, trend = 0.006 for aggressive cancer), whereas there was no evidence for a trend among those assigned to beta-carotene supplements. However, in the beta-carotene group, prostate cancer risk was reduced in each lycopene quintile relative to men with low lycopene and placebo. The only other notable association was a reduced risk of aggressive cancer with higher alpha-tocopherol levels that was not statistically significant. None of the associations for lycopene were confounded by age, smoking, body mass index, exercise, alcohol, multivitamin use, or plasma total cholesterol level. These results concur with a recent prospective dietary analysis, which identified lycopene as the carotenoid with the clearest inverse relation to the development of prostate cancer. The inverse association was particularly apparent for aggressive cancer and for men not consuming beta-carotene supplements. For men with low lycopene, beta-carotene supplements were associated with risk reductions comparable to those observed with high lycopene. These data provide further evidence that increased consumption of tomato products and other lycopene-containing foods might reduce the occurrence or progression of prostate cancer.

#257 Hayes RB, Ziegler RG, Gridley G, Swanson C, Greenberg RS, Swanson GM, Schoenberg JB, Silverman DT, Brown LM, Pottern LM, Liff J, Schwartz AG, Fraumeni JF Jr, Hoover RN Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, Maryland 20892, USA. hayesr@epndce.nci.nih.gov Dietary factors and risks for prostate cancer among blacks and whites in the United States. Cancer Epidemiol Biomarkers Prev 1999 Jan;8(1):25-34 Prostate cancer is the most common malignancy in men in the United States, with substantially higher rates among American blacks than whites. We carried out a population-based case-control study in three geographic areas of the United States to evaluate the reasons for the racial disparity in incidence rates. A total of 932 men (449 black men and 483 white men) who had been newly diagnosed with pathologically confirmed prostate cancer and 1201 controls (543 black men and 658 white men) were interviewed in person to elicit information on potential risk factors. This report evaluates the impact of dietary factors, particularly the consumption of animal products and animal fat, on the risk of prostate cancer among blacks and whites in the United States. Increased consumption (grams/day) of foods high in animal fat was linked to prostate cancer (independent of intake of other calories) among American blacks [by quartile of intake, odds ratio (OR) = 1.0 (referent), 1.5, 2.1, and 2.0; Ptrend = 0.007], but not among American whites [by quartile of intake, OR = 1.0 (referent), 1.6, 1.5, and 1.1; Ptrend = 0.90]. However, risks for advanced prostate cancer were higher with greater intake of foods high in animal fat among blacks [by quartile of intake, OR = 1.0 (referent), 2.2, 4.2, and 3.1; Ptrend = 0.006] and whites [by quartile of intake, OR = 1.0 (referent), 2.2, 2.6, and 2.4; Ptrend = 0.02]. Increased intake of animal fat as a proportion of total caloric intake also showed positive but weaker associations with advanced prostate cancer among blacks (Ptrend = 0.13) and whites (Ptrend = 0.08). No clear associations were found with vitamin A, calcium, or specific lycopene-rich foods. The study linked greater consumption of fat from animal sources to increased risk for prostate cancer among American blacks and to advanced prostate cancer among American blacks and whites. A reduction of fat from animal sources in the diet could lead to decreased incidence and mortality rates for prostate cancer, particularly among American blacks.

#287 Pastori M, Pfander H, Boscoboinik D, Azzi A Institute for Biochemistry and Molecular Biology, University of Bern, Bern, CH-3012, Switzerland. Lycopene in association with alpha-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochem Biophys Res Commun 1998 Sep 29;250(3):582-5 The effect of lycopene alone or in association with other antioxidants was studied on the growth of two different human prostate carcinoma cell lines (the androgen insensitive DU-145 and PC-3). It was found that lycopene alone was not a potent inhibitor of prostate carcinoma cell proliferation. However, the simultaneous addition of lycopene together with alpha-tocopherol, at physiological concentrations (less than 1 microM and 50 microM, respectively), resulted in a strong inhibitory effect of prostate carcinoma cell proliferation, which reached values close to 90 %. The effect of lycopene with alpha-tocopherol was synergistic and was not shared by beta-tocopherol, ascorbic acid and probucol.

#304 Fleshner NE, Klotz LH Department of Surgery, Toronto Sunnybrook Regional Cancer Center, University of Toronto, Canada. neil.fleshner@utoronto.ca Diet, androgens, oxidative stress and prostate cancer susceptibility. Cancer Metastasis Rev 1998-99;17(4):325-30 Prostate cancer is the most common human malignancy and the second leading cause of cancer deaths among men in Western nations. Descriptive epidemiologic data suggest that androgens and/or environmental exposures, such as diet (in particular, dietary fat), play an important role in prostatic carcinogenesis. One plausible link between diet and prostate cancer is oxidative stress. This process refers to the generation of reactive oxygen species, which can then trigger a host of pro-carcinogenic processes. Recent studies also indicate that androgens increase oxidative stress within human prostate cancer cell lines. Recent data from our institution indicate that oxidative stress is higher within the benign epithelium of prostate cancer patients than men without the disease. This confirms our hypothesis and suggests that antioxidants such as lycopene, vitamin E, and selenium may play an important role in preventing disease progression. Large-scale clinical trials with some of these agents are currently in the design phase.

#315 Grant WB NASA Langley Research Center, Hampton, VA, USA. wbgrant@norfolk.infi.net An ecologic study of dietary links to prostate cancer. Altern Med Rev 1999 Jun;4(3):162-9 BACKGROUND: The etiology of prostate cancer has not been fully resolved in the scientific and medical literature, although the non-fat portion of milk and calcium are emerging as leading dietary risk factors, with lycopene (found in tomatoes) and vitamin D apparently being risk reduction factors. METHODS: The ecologic (multi-country statistical) approach is used to study dietary links to prostate cancer. Mortality data from 1986 for various age groups in 41 countries are compared with national consumer macronutrient supply values for 1983 and tomato supply values for 1985. RESULTS: For 28 countries with more than five Kcal/day of tomatoes in the consumer supply, a linear combination of non-fat milk (risk factor) and tomatoes (risk reduction factor) was found to have the highest statistical association with prostate cancer mortality rates for men over the age of 35, with the Pearson regression coefficient (R2) for those aged 65-74 years = 0.67 and p < 0.001. For the 13 countries with fewer than six Kcal/day of tomatoes, non-fat milk had the highest association (R2 = 0.92, p < 0.001 for men aged 65-74 years). For 41 countries combined, the non-fat portion of milk had the highest association with prostate cancer mortality rates (R2 = 0.73, p < 0.001 for men aged 65-74 years). CONCLUSIONS: These results support the results of several cohort studies which found the non-fat portion of milk to have the highest association with prostate cancer, likely due to the calcium, and tomatoes to reduce the risk of prostate cancer, most likely due to lycopene.

#319 Rao AV, Fleshner N, Agarwal S Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada. v.rao@utoronto.ca Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case-control study. Nutr Cancer 1999;33(2):159-64 Dietary intake of tomatoes and tomato products containing lycopene, an antioxidant carotenoid, has been shown in recent studies to reduce the risk of cancer. This study was conducted to investigate the serum and prostate tissue lycopene and other major carotenoid concentrations in cancer patients and their controls. Serum lipid and protein oxidation was also measured. Twelve prostate cancer patients and 12 age-matched subjects were used in the study. Significantly lower serum and tissue lycopene levels (44%, p = 0.04; 78%, p = 0.050, respectively) were observed in the cancer patients than in their controls. Serum and tissue beta-carotene and other major carotenoids did not differ between the two groups (p = 0.395 and p = 0.280, respectively). Although there was no difference (p = 0.760) in serum lipid peroxidation between cancer patients and their controls (7.09 +/- 0.74 and 6.81 +/- 0.56 mumol/l, respectively), serum protein thiol levels were significantly lower among the cancer patients (p = 0.026). This study demonstrates that the status of lycopene but not other carotenoids in prostate cancer patients is different from controls. The role of dietary lycopene in preventing oxidative damage of biomolecules and thereby reducing the risk of prostate cancer needs to be evaluated in future studies.

#325 Kelloff GJ, Lieberman R, Steele VE, Boone CW, Lubet RA, Kopelovitch L, Malone WA, Crowell JA, Sigman CC National Cancer Institute, Division of Cancer Prevention, Chemoprevention Branch, Bethesda, MD 20892, USA. Chemoprevention of prostate cancer: concepts and strategies. Eur Urol 1999;35(5-6):342-50 Chemoprevention is the administration of agents to prevent induction and inhibit or delay progression of cancers. For prostate, as for other cancer targets, successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating chemopreventive efficacy. Agent requirements are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the observed chemopreventive activity. On this basis, promising chemopreventive drugs in prostate include retinoids, antiandrogens, antiestrogens, steroid aromatase inhibitors, 5alpha-reductase inhibitors, vitamins D and E, selenium, lycopene, and 2-difluoromethylornithine. Phase II trials are critical for evaluating chemopreventive efficacy. Cohorts in these trials should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen as endpoints. Many cohorts proposed for phase II trials are patients with previous cancers or premalignant lesions. For such patients, trials should be conducted within the context of standard treatment. Two cohorts currently used in phase II prostate cancer chemoprevention trials are patients with PIN and patients scheduled for prostate cancer surgery. Biomarkers should fit expected biological mechanisms, be assayed reliably and quantitatively, measured easily, and correlate to decreased cancer incidence. Protocols for adequately sampling tissue are essential. Changes in PIN provide prostate biomarkers with the ability to be quantified and a high correlation to cancer. PIN measurements include nuclear polymorphism, nucleolar size and number of nucleoli/nuclei, and DNA ploidy. Other potentially useful biomarkers are associated with cellular proliferation kinetics (e.g. PCNA and apoptosis), differentiation (e.g. blood group antigens, vimentin), genetic damage (e.g. LOH on chromosome 8), signal transduction (e.g. TGFalpha, TGFbeta, IGF-I, c-erbB-2 expression), angiogenesis, and biochemical changes (e.g. PSA levels).

#326 Thomas JA Department of Pharmacology, University of Texas Health Science Center, San Antonio, USA. Diet, micronutrients, and the prostate gland. Nutr Rev 1999 Apr;57(4):95-103 Diseases of the prostate gland, particularly adenocarcinoma and benign prostatic hyperplasia (BPH), are age-related. Prostate cancer is the most commonly occurring tumor in U.S. men. Differences in the incidence of this disease among ethnic populations are not due solely to genetic differences. Many efforts have been devoted to studying associations between nutrition and prostate cancer. The strongest association appears to be related to total fat intake and increased risk of this malignancy. Evidence also exists to suggest a role for certain micronutrients, such as zinc, selenium, vitamin E, lycopene, phytoestrogens, and phytosterols, although the role of nutrition and micronutrients in protection against prostate cancer is less convincing. Further research is necessary.

#340 Kumar NB, Besterman-Dahan K Department of Nutrition, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida 33612, USA. Nutrients in the Chemoprevention of Prostate Cancer: Current and Future Prospects. Cancer Control 1999 Nov;6(6):580-586 BACKGROUND: External factors such as diet and lifestyle may be important in the etiology of invasive prostate cancer. Specific features of prostate cancer, including high prevalence, long latency, and significant mortality and morbidity, provide the opportunities for chemoprevention. METHODS: The authors examine the experimental and epidemiological data demonstrating the chemopreventive activity, safety, and toxicity of chronic administration of these specific nutrients as chemopreventive agents in prostate cancer. RESULTS: Several nutrients have been identified as agents that inhibit mutagenesis and hyperproliferation or induce apoptosis or differentiation, which are critical characteristics for chemoprevention. Successful chemopreventive strategies require well-characterized agents, suitable cohorts, and reliable intermediate biomarkers of cancer for evaluating efficacy. Phytoestrogens/isoflavones, vitamins D and E, selenium, and lycopene have been identified as promising nutrients in the role of chemoprevention of prostate cancer. CONCLUSIONS: Clinical studies to evaluate the safety and effectiveness of these agents as future prospects in cancer chemoprevention, both individually and in combination, are warranted.

#360 Kristal AR, Cohen JH Cancer Prevention Research Program, Fred Hutchinson Cancer Research Center, Seattle, WA, USA. Invited commentary: tomatoes, lycopene, and prostate cancer. How strong is the evidence? Am J Epidemiol 2000 Jan 15;151(2):124-7; discussion 128-30 NO ABSTRACT

#361 Norrish AE, Jackson