Review of Clinical Studies Showing Lycopene and Reduced Risk of Prostate Cancer

• #59
  Clinton SK, Emenhiser C, Schwartz SJ, Bostwick DG, Williams AW, Moore BJ, Erdman JW Jr
  Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115-6084, USA.
  cis-trans lycopene isomers, carotenoids, and retinol in the human prostate.
  Cancer Epidemiol Biomarkers Prev 1996 Oct;5(10):823-833
  An evaluation of the Health Professionals Follow-Up Study has detected a lower prostate cancer risk associated with the greater consumption of tomatoes and related food products. Tomatoes are the primary dietary source of lycopene, a non-provitamin A carotenoid with potent antioxidant activity. Our goal was to define the concentrations of lycopene, other carotenoids, and retinol in paired benign and malignant prostate tissue from 25 men, ages 53 to 74, undergoing prostatectomy for localized prostate cancer. The concentrations of specific carotenoids in the benign and malignant prostate tissue from the same subject are highly correlated. Lycopene and all-trans beta-carotene are the predominant carotenoids observed, with means +/- SE of 0.80 +/- 0.08 nmol/g and 0.54 +/- 0.09, respectively. Lycopene concentrations range from 0 to 2.58 nmol/g, and all-trans beta-carotene concentrations range from 0.09 to 1.70 nmol/g. The 9-cis beta-carotene isomer, alpha-carotene, lutein, alpha-cryptoxanthin, zeaxanthin, and beta-cryptoxanthin are consistently detectable in prostate tissue. No significant correlations between the concentration of lycopene and the concentrations of any other carotenoid are observed. In contrast, strong correlations between prostate beta-carotene and alpha-carotene are noted (correlation coefficient, 0.88; P < 0.0001), as are correlations between several other carotenoid pairs, which reflects their similar dietary origins. Mean vitamin A concentration in the prostate is 1.52 nmol/g, with a range of 0.71 to 3.30 nmol/g. We further evaluated tomato-based food products, serum, and prostate tissue for the presence of geometric lycopene isomers using high-performance liquid chromatography with a polymeric C30 reversed phase column. All-trans lycopene accounts for 79 to 91% and cis lycopene isomers for 9 to 21% of total lycopene in tomatoes, tomato paste, and tomato soup. Lycopene concentrations in the serum of men range between 0.60 and 1.9 nmol/ml, with 27 to 42% all-trans lycopene and 58 to 73% cis-isomers distributed among 12 to 13 peaks, depending upon their chromatographic resolution. In striking contrast with foods, all-trans lycopene accounts for only 12 to 21% and cis isomers for 79 to 88% of total lycopene in benign or malignant prostate tissues. cis Isomers of lycopene within the prostate are distributed among 14 to 18 peaks. We conclude that a diverse array of carotenoids are found in the human prostate with significant intra-individual variation. The presence of lycopene in the prostate at concentrations that are biologically active in laboratory studies supports the hypothesis that lycopene may have direct effects within the prostate and contribute to the reduced prostate cancer risk associated with the reduced prostate cancer risk associated with the consumption of tomato-based foods. The future identification and characterization of geometric lycopene isomers may lead to the development of novel agents for chemoprevention studies.
  
  
• #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 RT, Sharpe SJ, Skeaff CM
  Department of Community Health, University of Auckland, New Zealand.
  Prostate cancer and dietary carotenoids.
  Am J Epidemiol 2000 Jan 15;151(2):119-23
  This population-based case-control study investigated associations between prostate cancer risk and dietary intake of the carotenoids beta-carotene and lycopene and their major plant food sources, including carrots, green leafy vegetables, and tomato-based foods. The study was carried out in Auckland, New Zealand, during 1996-1997 and recruited 317 prostate cancer cases and 480 controls. The authors found that dietary intake of beta-carotene and its main vegetable sources was largely unassociated with prostate cancer risk, whereas intake of lycopene and tomato-based foods was weakly associated with a reduced risk. These results suggest that in contrast to the findings regarding many types of cancers, vegetables rich in beta-carotene are not protective against prostate cancer. However, lycopene from tomato-based foods was found to be associated with a small reduction in risk.
  
  
• #363
  Grant WB
  Calcium, lycopene, vitamin D and prostate cancer.
  Prostate 2000 Feb 15;42(3):243
  No abstract.
  
  
• #381
  Clinton SK
  The dietary antioxidant network and prostate carcinoma.
  Cancer 1999 Nov 1;86(9):1629-31
  No abstract.
  
  
• #439
  Guttenplan JB, Chen M, Kosinska W, Thompson S, Zhao Z, Cohen LA
  Division of Basic Sciences/Biochemistry, New York University, Dental Center, 345 E. 24th St., New York, 10100, NY, USA
  Effects of a lycopene-rich diet on spontaneous and benzo[a]pyrene induced mutagenesis in porstate, colon, and lung of the lac Z mouse.
  Cancer Lett 2001 Mar 10;164(1):1-6
  Consumption of lycopene has been associated with reduced risk of prostate cancer. We have investigated the effects of lycopene, fed as a lycopene-rich tomato oleoresin (LTO) at two doses, on in vivo mutagenesis in prostate, colon, and lungs of lacZ mice. Both short-term benzo[a]pyrene (BaP)- induced and long-term spontaneous mutagenesis were monitored. Non-significant inhibition of spontaneous mutagenesis in prostate and colon was observed at the higher dose of LTO, and the observation of inhibition in colon was facilitated by an unusually high spontaneous mutagenesis rate. BaP-induced mutagenesis was slightly inhibited by LTO in prostate. However, enhancement of BaP-induced-mutagenesis was observed in colon and lung. These results indicate that any antimutagenic effects of LTO may be organospecific.
  
  
• #444
  Cristoni A, Di Pierro F, Bombardelli E
  Scientific Department, Indena S.p.A., Viale Ortles 12, 20139, Milan, Italy
  Botanical derivatives for the prostate.
  Fitoterapia 2000 Aug;71 Suppl 1:S21-S28
  The prostate, after the age of 45 years, may undergo benign hyperplasia (BPH). Its etiology has not yet been completely explained, but different factors play a major role in its occurrence, among them, the sexual hormones (with a fundamental role of 5 alpha reductase). The 5-alpha reductase activity and inflammatory aspects in the prostate tissue can be effectively controlled with the use of highly standardized plant extracts (Pygeum africanum, Serenoa repens, etc.), which yield excellent results in the prophylaxis and treatment of the symptoms linked to prostate hypertrophy. The prostate tissue is not affected only by benign diseases but may also be subject to neoplastic transformation. From an epidemiological point of view, a vegetable derivative, lycopene, was linked with a lower occurrence of prostate carcinoma. A recent clinical study demonstrated that lycopene might not only prevent prostate cancer but also have therapeutic effects.
  
  
• #483
  Imaida K, Tamano S, Kato K, Ikeda Y, Asamoto M, Takahashi S, Nir Z, Murakoshi M, Nishino H, Shirai T
  1st Department of Pathology Nagoya City University Medical School, 1-Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan. imaida@med.nagoya-cu.ac.jp
  Lack of chemopreventive effects of lycopene and curcumin on experimental rat prostate carcinogenesis.
  Carcinogenesis 2001 Mar;22(3):467-72
  The chemopreventive efficacy of lycopene and curcumin with regard to prostate carcinogenesis was investigated using 3,2'-dimethyl-4-aminobiphenol (DMAB)- and 2-amino-1-methylimidazo[4,5-b]pyridine (PhIP)-induced rat ventral prostate cancer models. Three 60 week experiments with male F344 rats were carried out. In the first DMAB was given for the first 20 weeks and lycopene or curcumin were administered concomitantly or subsequently at dietary doses of 15 and 500 p.p.m., respectively. In the second experiment lycopene and curcumin were given to rats pretreated with DMAB at doses of 5, 15 or 45 p.p.m. or 100 or 500 p.p.m. In the third PhIP was selected as an initiator for prostate carcinogenesis and administered for 20 weeks. Rats were then fed a diet containing lycopene at a dose of 45 p.p.m. or curcumin at a dose of 500 p.p.m. or both together. Chemopreventive effects of lycopene and curcumin on development of DMAB-induced ventral prostate carcinomas were observed only in the first experiment and no confirmation of inhibition potential was obtained in the following studies. Neither summational nor synergistic chemoprevention was evident. It is concluded from the present data that, overall, neither lycopene nor curcumin can consistently prevent rat prostate carcinogenesis.
  
  
• #550
  Mucci LA, Tamimi R, Lagiou P, Trichopoulou A, Benetou V, Spanos E, Trichopoulos D.
  Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA, Department of Hygiene and Epidemiology, University of Athens Medical School, and Biomed International Diagnostic Center, Athens, Greece.
  Are dietary influences on the risk of prostate cancer mediated through the insulin-like growth factor system?
  BJU Int 2001 Jun;87(9):814-20
  OBJECTIVES: To investigate whether dietary factors that appear to affect the risk of prostate cancer may be similarly associated with serum levels of insulin-like growth factor 1 (IGF-1). Patients and methods In the context of a case-control study, 112 men were admitted to three teaching hospitals in Athens, Greece, for disorders other than cancer. Sociodemographic data and detailed histories of smoking, alcohol and coffee consumption were recorded. A validated food-frequency questionnaire was administered by an interviewer and serological measurements of IGF-1 and its binding protein-3 conducted. RESULTS: IGF-1 declined significantly by almost 25% among men aged >75 years and there was a small reduction in IGF-1 levels with increased alcohol intake, with a mean (95% confidence interval, CI) change of -1.6 (- 2.2 to -0.9)% for an increment of one drink per day. There was no evidence for an effect of either smoking or coffee consumption on IGF-1 level. Among foods, the consumption of cooked tomatoes was substantially and significantly inversely associated with IGF-1 levels, with a mean (95% CI) change of -31.5 (- 49.1 to -7.9)% for an increment of one serving per day. CONCLUSIONS: The strongest known dietary risk factor for prostate cancer (lycopene deficit, as reflected in a reduced intake of cooked tomatoes) and an important endocrine factor in the aetiology of this disease (IGF-1) seem to be related in a way that suggests that at least one, and perhaps more, exogenous factors in the development of prostate cancer may be mediated through the IGF-1 system.
  
  
• #559
  Matlaga BR, Hall MC, Stindt D, Torti FM.
  Department of Urology and Comprehensive Cancer Center, Wake Forest University School of Medicine, Winston-Salem, North Carolina.
  Response of hormone refractory prostate cancer to lycopene.
  J Urol 2001 Aug;166(2):613
  No abstract.
  
  
• #564
  Lu QY, Hung JC, Heber D, Go VL, Reuter VE, Cordon-Cardo C, Scher HI, Marshall JR, Zhang ZF.
  Center for Human Nutrition, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095, USA. qlu@mednet.ucla.edu
  Inverse associations between plasma lycopene and other carotenoids and prostate cancer.
  Cancer Epidemiol Biomarkers Prev 2001 Jul;10(7):749-56
  Although dietary intake of tomatoes and tomato products containing lycopene has been reported to reduce the risk of prostate cancer, few studies have been done on the relationship between plasma lycopene and other carotenoids and prostate cancer. This case-control study was conducted to investigate the effects of plasma lycopene, other carotenoids, and retinol, as well as alpha- and gamma-tocopherols on the risk of prostate cancer. The study included 65 patients with prostate cancer and 132 cancer-free controls; all of them were interviewed using a standard epidemiological questionnaire at the Memorial Sloan-Kettering Cancer Center from 1993 to 1997. Plasma levels of carotenoids, retinol, and tocopherols were measured by high performance liquid chromatography. An unconditional logistic regression model was used in bivariate and multivariate analyses using Statistical Analysis System (SAS). After adjusting for age, race, years of education, daily caloric intake, pack-years of smoking, alcohol consumption, and family history of prostate cancer, significantly inverse associations with prostate cancer were observed with plasma concentrations of the following carotenoids: lycopene [odds ratio (OR), 0.17; 95% confidence interval (CI), 0.04-0.78; P for trend, 0.0052] and zeaxanthin (OR, 0.22; 95% CI, 0.06-0.83; P for trend, 0.0028) when comparing highest with lowest quartiles. Borderline associations were found for lutein (OR, 0.30; 95% CI, 0.09-1.03; P for trend, 0.0064) and beta-cryptoxanthin (OR, 0.31; 95% CI, 0.08-1.24; P for trend, 0.0666). No obvious associations were found for alpha- and beta-carotenes, retinol, and alpha- and gamma-tocopherols. Our study confirmed the inverse associations between lycopene, other carotenoids such as zeaxanthin, lutein, and beta-cryptoxanthin, and prostate cancer. This study provides justification for further research on the associations between lycopene and other antioxidants and the risk of prostate cancer.
  
  
• #567
  de la Taille, A.; Katz, A.; Vacherot, F.; Saint, F.; Salomon, L.; Cicco, A.; Abbou, C. C.; Chopin, D. K.
  Centre de Recherche chirurgicale, Service d'Urologie, H .pital Henri Mondor, 54, boulevard du Mar .chal de Lattre de Tassigny, F94100 Cr.teil. ad399@hotmail.com
  Cancer of the prostate: influence of nutritional factors. Vitamins, antioxidants and trace elements.
  Presse Med VOL. 30 NO. 11 2001 Mar 24 PP. 557-60
  CANCER OF THE PROSTATE AND VITAMINS: Four vitamins have been studied, vitamins A, E, D and C. the results of these studies have been contradictory. Vitamin A and vitamin E would have a protective effect. ANTIOXIDANTS: Carotenes have an activity similar to that of vitamin A. Beta-carotene was positively associated with risk of cancer of the prostate in one study while two others were unable to demonstrate any relationship. Lycopene, the red color in fruits and vegetables, particularly tomatoes, would contribute to a lower risk of prostate cancer. TRACE ELEMENTS: Cadmium would increase the risk of cancer while selenium would have a protective effect. However studies concerning selenium carry certain methodological biases.
  
  
• #570
  Schroder, Fritz H.; Kranse, Ries; Dijk, Mathilde A.; Blom, Jan H. M.; van Kemenade, Monique; Dagnelie, Pieter C.; Tijburg, Lianne M.; Weststrate, Jan A.
  Rotterdam, Netherlands
  Dietary intervention in prostate cancer patients. Results of a randomized, double blind placebo controlled cross-over study.
  Journal of Urology VOL. 165 NO. 5 Supplement May, 2001 PP. 65.
  June 02-07, 2001 Annual Meeting of the American Urological Association, Inc.
  
  
• #597
  Kucuk O, Sarkar FH, Sakr W, Djuric Z, Pollak MN, Khachik F, Li YW, Banerjee M, Grignon D, Bertram JS, Crissman JD, Pontes EJ, Wood DP Jr.
  Division of Hematology and Oncology, Wayne State University, and Barbara Ann
  Karmanos Cancer Institute, Detroit, MI 48201, USA. kucuko@karmanos.org
  Phase II randomized clinical trial of lycopene supplementation before radical prostatectomy.
  Cancer Epidemiol Biomarkers Prev 2001 Aug;10(8):861-868
  An inverse association has been observed between dietary intake of lycopene and the risk of prostate cancer. We investigated the effects of lycopene supplementation in patients with prostate cancer. Twenty-six men with newly diagnosed, clinically localized (14 T(1) and 12 T(2)) prostate cancer were randomly assigned to receive 15 mg of lycopene (n = 15) twice daily or no supplementation (n=11) for 3 weeks before radical prostatectomy. Biomarkers of differentiation and apoptosis were assessed by Western blot analysis on benign and malignant parts of the prostate gland. Prostatectomy specimens were entirely embedded, step-sectioned, and evaluated for pathological stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1 (IGF-1), IGF binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. Eleven (73%) subjects in the intervention group and two (18%) subjects in the control group had no involvement of surgical margins and/or extra-prostatic tissues with cancer (P=0.02). Twelve (84%) subjects in the lycopene group and five (45%) subjects in the control group had tumors <4 ml in size (P=0.22). Diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia was present in 10 (67%) subjects in the intervention group and in 11 (100%) subjects in the control group (P=0.05). Plasma prostate-specific antigen levels decreased by 18% in the intervention group, whereas they increased by 14% in the control group (P=0.25). Expression of connexin 43 in cancerous prostate tissue was 0.63 0.19 absorbance in the lycopene group compared with 0.25 0.08 in the control group (P=0.13). Expression of bcl-2 and bax did not differ significantly between the two study groups. IGF-1 levels decreased in both groups (P = 0.0002 and P = 0.0003, respectively). The results suggest that lycopene supplementation may decrease the growth of prostate cancer. However, no firm conclusions can be drawn at this time because of the small sample size.
  
  
• #622
  Bowen, P. E. University of Illinois, Chicago, IL, 60612: pbowen@uic.edu, USA
  Tomato sauce supplementation reduces DNA damage in men with prostate cancer. Abstracts of Papers American Chemical Society VOL. 222 NO. 1-2,2001 PP.
  AGFD129.
  American Chemical Society CONFERENCE DATE August 26-30, 2001
  CONFERENCE TITLE: 222nd National Meeting of the American Chemical Society
  No abstract.
  
  
• #636
  Kotake-Nara E, Kushiro M, Zhang H, Sugawara T, Miyashita K, Nagao A.
  Department of Bioresources Chemistry, Graduate School of Fisheries Science, Hokkaido University, 3-1-1 Hakodate 041-8611, Japan and. National Food Research Institute, 2-1-12 Kannondai, Tsukuba, Ibaraki 305-8642, Japan.
  Carotenoids Affect Proliferation of Human Prostate Cancer Cells.
  J Nutr 2001 Dec;131(12):3303-3306
  We investigated whether various carotenoids present in foodstuffs were potentially involved in cancer-preventing action on human prostate cancer. The effects of 15 kinds of carotenoids on the viability of three lines of human prostate cancer cells, PC-3, DU 145 and LNCaP, were evaluated. When the prostate cancer cells were cultured in a carotenoid-supplemented medium for 72 h at 20 &mgr;mol/L, 5,6-monoepoxy carotenoids, namely, neoxanthin from spinach and fucoxanthin from brown algae, significantly reduced cell viability to 10.9 and 14.9% for PC-3, 15.0 and 5.0% for DU 145, and nearly zero and 9.8% for LNCaP, respectively. Acyclic carotenoids such as phytofluene, zeta-carotene and lycopene, all of which are present in tomato, also significantly reduced cell viability. On the other hand, phytoene, canthaxanthin, beta-cryptoxanthin and zeaxanthin did not affect the growth of the prostate cancer cells. DNA fragmentation of nuclei in neoxanthin- and fucoxanthin-treated cells was detected by in situ TdT-mediated dUTP nick end labeling (TUNEL) assay. Neoxanthin and fucoxanthin were found to reduce cell viability through apoptosis induction in the human prostate cancer cells. These results suggest that ingestion of leafy green vegetables and edible brown algae rich in neoxanthin and fucoxanthin might have the potential to reduce the risk of prostate cancer.
  
  
• #643
  Kucuk O, Wood DP Jr.
  Re: Response of hormone refractory prostate cancer to lycopene.
  J Urol 2002 Feb;167(2 Pt 1):651
  No abstract available.
  
  
• #658
  van Breemen RB, Xu X, Viana MA, Chen L, Stacewicz-Sapuntzakis M, Duncan C, Bowen PE, Sharifi R.
  Department of Medicinal Chemistry and Pharmacognosy, General Clinical Research Center, and Department of Human Nutrition and Dietetics, University of Illinois at Chicago, Chicago, Illinois 60612, and Department of Urology, University of Illinois at Chicago and Westside Veterans Administration Hospital, Chicago, Illinois 60612.
  Liquid Chromatography-Mass Spectrometry of cis- and all-trans-Lycopene in Human Serum and Prostate Tissue after Dietary Supplementation with Tomato Sauce.
  J Agric Food Chem 2002 Apr 10;50(8):2214-2219
  Several epidemiological studies suggest a lower incidence of prostate cancer in men who routinely consume tomato products. Tomatoes are the primary dietary source of lycopene, which is among the most potent antioxidants of the carotenoids. Men with clinical stage T1 or T2 prostate adenocarcinoma were recruited (n = 32) and consumed tomato sauce based pasta dishes for 3 weeks (equivalent to 30 mg of lycopene per day) before radical prostectomy. Prostate tissue from needle biopsy just before intervention and prostectomy after supplementation from a subset of 11 subjects was evaluated for both total lycopene and lycopene geometrical isomer ratios. A gradient HPLC system using a C(18) column with UV-vis absorbance detection was used to measure total lycopene. Because the absorbance detector was insufficiently sensitive, HPLC with a C(30) column and positive ion atmospheric pressure chemical ionization mass spectrometric (LC-MS) detection was developed as a new assay to measure the ratio of lycopene cis/trans isomers in these samples. The limit of detection of the LC-MS method was determined to be 0.93 pmol of lycopene on-column, and a linear response was obtained over 3 orders of magnitude. Total lycopene in serum increased 2.0-fold from 35.6 to 69.9 &mgr;g/dL (from 0.664 to 1.30 &mgr;M) as a result of dietary supplementation with tomato sauce, whereas total lycopene in prostate tissue increased 3.0-fold from 0.196 to 0.582 ng/mg of tissue (from 0.365 to 1.09 pmol/mg). all-trans-Lycopene and at least 14 cis-isomer peaks were detected in prostate tissue and serum. The mean proportion of all-trans-lycopene in prostate tissue was approximately 12.4% of total lycopene before supplementation but increased to 22.7% after dietary intervention with tomato sauce. In serum there was only a 2.8% but statistically significant increase in the proportion of all-trans-lycopene after intervention. These results indicate that short-term supplementation with tomato sauce containing primarily all-trans-lycopene (83% of total lycopene) results in substantial increases in total lycopene in serum and prostate and a substantial increase in all-trans-lycopene in prostate but relatively less in serum.
  
  
• #670
  Giovannucci E, Rimm EB, Liu Y, Stampfer MJ, Willett WC.
  Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA. edward.giovannucci@channing.harvard.edu
  A prospective study of tomato products, lycopene, and prostate cancer risk.
  J Natl Cancer Inst 2002 Mar 6;94(5):391-8
  BACKGROUND: Some data, including our findings from the Health Professionals
  Follow-Up Study (HPFS) from 1986 through January 31, 1992, suggest that frequent intake of tomato products or lycopene, a carotenoid from tomatoes, is associated with reduced risk of prostate cancer. Overall, however, the data are inconclusive. We evaluated additional data from the HPFS to determine if the association would persist. METHODS: We ascertained prostate cancer cases from 1986 through January 31, 1998, among 47 365 HPFS participants who completed dietary questionnaires in 1986, 1990, and 1994. We used pooled logistic regression to compute multivariate relative risks (RR) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: From 1986 through January 31, 1998, 2481 men in the study developed prostate cancer. Results for the period from 1992 through 1998 confirmed our previous findings---that frequent tomato or lycopene intake was associated with a reduced risk of prostate cancer. Similarly, for the entire period of 1986 through 1998, using the cumulative average of the three dietary questionnaires, lycopene intake was associated with reduced risk of prostate cancer (RR for high versus low quintiles = 0.84; 95% CI = 0.73 to 0.96; P(trend) =.003); intake of tomato sauce, the primary source of bioavailable lycopene, was associated with an even greater reduction in prostate cancer risk (RR for 2+ servings/week versus <1 serving/month = 0.77; 95% CI = 0.66 to 0.90; P(trend)<.001), especially for extraprostatic cancers (RR = 0.65; 95% CI = 0.42 to 0.99). These associations persisted in analyses controlling for fruit and vegetable consumption and for olive oil use (a marker for Mediterranean diet) and were observed separately in men of Southern European or other Caucasian ancestry. CONCLUSION: Frequent consumption of tomato products is associated with a lower risk of prostate cancer. The magnitude of the association was moderate enough that it could be missed in a small study or one with substantial errors in measurement or based on a single dietary assessment.
  
  
• #682
  Vogt TM, Mayne ST, Graubard BI, Swanson CA, Sowell AL, Schoenberg JB, Swanson
  GM, Greenberg RS, Hoover RN, Hayes RB, Ziegler RG.
  Department of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA. vogtt@exchange.nih.gov
  Serum lycopene, other serum carotenoids, and risk of prostate cancer in US Blacks and Whites.
  Am J Epidemiol 2002 Jun 1;155(11):1023-32
  Epidemiologic studies investigating the relation between individual carotenoids and risk of prostate cancer have produced inconsistent results. To further explore these associations and to search for reasons prostate cancer incidence is over 50% higher in US Blacks than Whites, the authors analyzed the serum levels of individual carotenoids in 209 cases and 228 controls in a US multicenter, population-based case-control study (1986-1989) that included comparable numbers of Black men and White men aged 40-79 years. Lycopene was inversely associated with prostate cancer risk (comparing highest with lowest quartiles, odds ratio (OR) = 0.65, 95% confidence interval (CI): 0.36, 1.15; test for trend, p = 0.09), particularly for aggressive disease (comparing extreme quartiles, OR = 0.37, 95% CI: 0.15, 0.94; test for trend, p = 0.04). Other carotenoids were positively associated with risk. For all carotenoids, patterns were similar for Blacks and Whites. However, in both the controls and the Third National Health and Nutrition Examination Survey, serum lycopene concentrations were significantly lower in Blacks than in Whites, raising the possibility that differences in lycopene exposure may contribute to the racial disparity in incidence. In conclusion, the results, though not statistically significant, suggest that serum lycopene is inversely related to prostate cancer risk in US Blacks and Whites.
  
  
• #687
  Kotake-Nara E, Kim SJ, Kobori M, Miyashita K, Nagao A.
  Department of Bioresources Chemistry, Graduate School of Fisheries Science, Hokkaido University, Japan.
  Acyclo-retinoic acid induces apoptosis in human prostate cancer cells.
  Anticancer Res 2002 Mar-Apr;22(2A):689-95
  Acyclo-retinoic acid, a novel acyclic analogue of all-trans-retinoic acid, has been previously isolated as one of the in vitro oxidation products of lycopene. The effect of acyclo-retinoic acid on the growth of human prostate cancer cells was compared with those of the four retinoids: all-trans-retinoic acid, geranylgeranoic acid, 9-cis-retinoic acid and N-(4-hydroxyphenyl)retinamide. When prostate cancer cells, PC-3, DU 145 and LNCaP, were cultured in a retinoid-supplemented medium, acyclo-retinoic acid remarkably reduced the viability of the cells except for LNCaP. This effect was significantly higher than that of geranylgeranoic acid, all-trans-retinoic acid and 9-cis-retinoic acid, but was comparable to that of N-(4-hydroxyphenyl)retinamide. DNA fragmentations of nuclei in PC-3 and DU 145 cells treated with acyclo-retinoic acid were detected by in situ TUNEL assay. Furthermore, an apoptotic DNA ladder was observed in PC-3 cells. These results showed that acyclo-retinoic acid reduced cell viability by inducing apoptosis in human prostate cancer cells.
  
  
• #699
  McMILLAN DC, Talwar D, Sattar N, Underwood M, St J O'Reilly D, McARDLE C.
  University Department of Surgery, Glasgow
  The relationship between reduced vitamin antioxidant concentrations and the systemic inflammatory response in patients with common solid tumours.
  Clin Nutr 2002 Apr;21(2):161-164
  Background and Aims: The majority of patients with advanced cancer have reduced circulating concentrations of the vitamin antioxidants including retinol, alpha-tocopherol and carotenoids. However, the basis of this reduction is not known. Vitamin antioxidant concentrations have been reported to be correlated with a systemic inflammatory response (as evidenced by C-reactive protein) in normal subjects and in patients with lung cancer. In order to determine whether this relationship was independent of tumour type patients other common solid tumours were studied. Methods: Fasting circulating concentrations of vitamin antioxidants and C-reactive protein were measured in normal subjects (n=30) and patients with breast (n=15), prostate (n=l5) and colorectal cancer (n=11). Results: Concentrations of C-reactive protein were higher (P<0.0001) and vitamin antioxidants lower (P<0.0001) in the cancer patients. In normal subjects and cancer patients, C-reactive protein concentrations were inversely correlated with circulating concentrations of retinol (r(2)=0.162), alpha-tocopherol (r(2)=0.297), lutein (r(2)=0.256), lycopene (r(2)=-0.171), alpha-(r(2)=0.140) and beta-carotene (r(2)=0.254): (all P<0.001). Conclusions: Concentrations of retinol, alpha -tocopherol and carotenoids are inversely associated with the magnitude of the systemic inflammatory response. These relationships appear to be independent of the presence and type of cancer.
  
  
• #704
  Miller EC, Giovannucci E, Erdman JW Jr, Bahnson R, Schwartz SJ, Clinton SK.
  Division of Hematology and Oncology, James Cancer Hospital, Solove Research Institute, Ohio State University Medical Center, Columbus, OH, USA.
  Tomato products, lycopene, and prostate cancer risk.
  Urol Clin North Am 2002 Feb;29(1):83-93
  Several case-control and large prospective studies focusing on dietary assessment suggest that the intake of tomatoes and tomato products may be associated with a lower risk of prostate cancer [18]. Although less certain at present, the accumulated data suggest that the benefit may be most pronounced in the protection against more advanced or aggressive prostate cancer. It is possible that lycopene is one of the compounds in raw and processed tomato products that may contribute to a lower risk of prostate cancer; however, this hypothesis remains to be further investigated. Other carotenoids and phytochemicals in tomato products may also contribute to the proposed health benefits. Food processing does not seem to reduce the benefits but may, in fact, enhance the bioavailability of beneficial components. The reported correlations or associations between the consumption of tomato products and prostate cancer risk should not be interpreted as causal until additional data are available from a variety of studies in different populations. Ideally, randomized controlled intervention studies would provide an ultimate test of the tomato/lycopene hypothesis; however, the expense, long duration of exposure, and the near universal consumption of tomato products among Americans make a dietary intervention study difficult to undertake. It is reasonable to recommend to the general population the consumption of tomato products at approximately one serving per day or five servings per week as part of an overall healthy dietary pattern that may reduce the risks of prostate cancer, other malignancies, or other chronic diseases. This recommendation is consistent with current dietary guidelines to increase fruit and vegetable consumption to lower the risk of heart disease and many types of cancer [38]. Nutritional prevention of prostate cancer is very different from the use of dietary or nutritional treatments for established prostate cancer. The use of lycopene and other extracts for the treatment of prostate cancer is a separate issue that warrants individual attention and investigation.
  
  
• #706
  Cohen LA.
  American Health Foundation, Valhalla, New York 10595, USA. Lcohen@AHF.org
  Nutrition and prostate cancer: a review.
  Ann N Y Acad Sci 2002 Jun;963:148-55
  Despite intense efforts, little is known about the etiology of prostate cancer, and treatment of advanced forms of the disease has had limited success. Nonetheless, epidemiologic studies combined with animal model and in vitro experiments indicate that natural components of the diet, including n-3 PUFA, the carotenoid lycopene, and the trace element selenium, may serve as chemopreventive agents that suppress the growth and dissemination of neoplastic prostate cells. Until further study, however, soy isoflavones should be viewed with some caution, especially as adjuvant's to chemotherapy, in patients with hormone-refractory prostate cancer. Future studies, using different forms and doses of selenium and tomato carotenoids, may shed new light on the etiology and prevention of prostate cancer.
  
  
• #710
  Schuurman AG, Goldbohm RA, Brants HA, van den Brandt PA.
  Department of Epidemiology, Maastricht University, PO Box 616, 6200 MD
  Maastricht, The Netherlands.
  A prospective cohort study on intake of retinol, vitamins C and E, and carotenoids and prostate cancer risk (Netherlands). Cancer Causes Control 2002 Aug;13(6):573-82
  OBJECTIVES: The roles of retinol, vitamins C and E, and carotenoids as risk factors for prostate carcinoma are still questionable. We evaluated these in the Netherlands Cohort Study. METHODS: The cohort study consisted of 58,279 men ages 55-69 years at baseline in 1986. After 6.3 years of follow-up, 642 incident prostate carcinoma cases were available for analysis. Intakes of retinol, vitamins C and E, and several carotenoids were measured by means of a 150-item semi-quantitative food-frequency questionnaire. RESULTS: In multivariate analyses a positive association with prostate cancer risk was observed for intake of beta-cryptoxanthin. Rate ratios (RRs) in increasing quintiles were 1.00 (ref), 0.94, 1.01, 1.16, 1.41; p-trend < 0.01. For intake of retinol, vitamins C and E and other carotenoids (alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin) no effect on overall prostate cancer risk was found. RRs for vitamin supplement use were decreased, but not significantly. Among nondrinkers, nonsignificant inverse associations were observed for intake of retinol, alpha-carotene, and beta-carotene (RRs, highest vs lowest quintile, were 0.23, 0.60, and 0.76, respectively). Among drinkers, beta-cryptoxanthin was positively associated (RR highest vs lowest quintile = 1.40). CONCLUSIONS: These data show a positive association between beta-cryptoxanthin and prostate cancer risk. Our study also shows inverse associations for retinol, alpha-carotene, and beta-carotene among nondrinkers; this suggests an interaction between vitamins and alcohol consumption, which needs confirmation. Lycopene was not associated with prostate cancer.
  
  
• #746
  van Gils CH, Bostick RM, Stern MC, Taylor JA.
  Molecular and Genetic Epidemiology Section, Laboratory of Molecular Carcinogenesis. National Institute of Environmental Health Sciences, NIH, Research Triangle Park, North Carolina 27709, USA.
  Differences in base excision repair capacity may modulate the effect of dietary antioxidant intake on prostate cancer risk: an example of polymorphisms in the XRCC1 gene. Cancer Epidemiol Biomarkers Prev 2002 Nov;11(11):1279-84
  We propose a hypothesis that differences in base excision repair capacity modulate the effect of dietary antioxidant intake on prostate cancer risk. As a preliminary test of this hypothesis, we conducted a pilot case-control study to evaluate prostate cancer risk in men with polymorphisms in the XRCC1 gene, a key player in base excision repair, across different strata of antioxidant intake. Seventy-seven prostate cancer patients and 183 community controls, for whom we have detailed dietary information, were frequency matched on age and race. We found a somewhat lower prostate cancer risk for men with one or two copies of the variant alleles at the XRCC1 codons 194 and 399 than for those who were homozygous for the common allele [codon 194: odds ratio (OR) = 0.8; 95% confidence interval (CI), 0.4-1.8 and codon 399: OR = 0.8; 95% CI, 0.5-1.3]. The variant at codon 280 was associated with a slightly increased prostate cancer risk (OR = 1.5; 95% CI, 0.7-3.6). Only the codon 399 polymorphism occurred frequently enough to investigate its joint effect with antioxidant intake. Prostate cancer risk was highest among men who were homozygous for the common allele at codon 399 and had low dietary intake of vitamin E (OR = 2.4; 95% CI, 1.0-5.6) or lycopene (OR = 2.0; 95% CI, 0.8-4.9), whereas low intake of these antioxidants in men without this genotype hardly increased prostate cancer risk. The polymorphism did not modulate risk associated with low intake of vitamin C, A, or beta-carotene. The data give some support for our hypothesis but should be regarded as preliminary, because it is limited by small sample size. We discuss what kind of data and what kind of studies are needed for future evaluation of this hypothesis.
  
  
• #753
  Bowen P, Chen L, Stacewicz-Sapuntzakis M, Duncan C, Sharifi R, Ghosh L, Kim HS, Christov-Tzelkov K, van Breemen R.
  Department of Human Nutrition and Dietetics, m/c 517, University of Illinois, 1919 West Taylor Street, Chicago, IL 60612, USA. pbowen@uic.edu
  Tomato sauce supplementation and prostate cancer: lycopene accumulation and modulation of biomarkers of carcinogenesis.
  Exp Biol Med (Maywood) 2002 Nov;227(10):886-93
  As part of a randomized placebo-controlled study to evaluate the effect of lycopene supplementation on DNA damage in men with prostate cancer, a nonrandomized 5th arm using tomato sauce was included and reported here. Thirty-two patients with localized prostate adenocarcinoma consumed tomato sauce-based pasta dishes for 3 weeks (30 mg of lycopene/day) before their scheduled radical prostatectomy. Prostate tissue was obtained as biopsies at baseline and as resected tissue at the time of the prostatectomy. Serum and prostate lycopene, serum prostate specific antigen (PSA) concentrations, and leukocyte DNA 8-OH-deoxyguanosine/deoxyguanosine (8OHdG) were measured at baseline and at the end of the intervention. Cancer cells in paraffin sections of prostate biopsies and postintervention resected tissue were compared for 8OHdG staining and for apoptosis. Adherence to the daily consumption of tomato-based entrees was 81.6% of the intended dose, and serum and prostate lycopene concentrations increased 1.97- and 2.92-fold (P < 0.001), respectively. Mean serum PSA concentrations decreased by 17.5% (P < 0.002) and leukocyte 8OHdG decreased by 21.3% (P < 0.005) after tomato sauce consumption. Resected tissues from tomato sauce-supplemented patients had 28.3% lower prostate 8OHdG compared with the nonstudy control group (P < 0.03). Cancer cell 8OHdG staining of Gleason Score-matched resected prostate sections was reduced by 40.5% in mean nuclear density (P < 0.005) and by 36.4% in mean area (P < 0.018) compared with the presupplementation biopsy. Apoptotic index was higher in hyperplastic and neoplastic cells in the resected tissue after supplementation. These data taken as a whole indicate significant uptake of lycopene into prostate tissue and a reduction in DNA damage in both leukocyte and prostate tissue. Whether reduction in DNA damage to prostate cancer cells is beneficial awaits further research, although reduction in serum PSA concentrations is promising.
  
  
• #754
  Kucuk O, Sarkar FH, Djuric Z, Sakr W, Pollak MN, Khachik F, Banerjee M, Bertram JS, Wood DP Jr.
  Division of Hematology and Oncology, 3990 John R, Barbara Ann Karmanos Cancer
  Institute, Wayne State University, 5 Hudson, Detroit, MI 48201, USA.
  kucuko@karmanos.org
  Effects of lycopene supplementation in patients with localized prostate cancer.
  Exp Biol Med (Maywood) 2002 Nov;227(10):881-5
  Epidemiological studies have shown an inverse association between dietary intake of lycopene and prostate cancer risk. We conducted a clinical trial to investigate the biological and clinical effects of lycopene supplementation in patients with localized prostate cancer. Twenty-six men with newly diagnosed prostate cancer were randomly assigned to receive a tomato oleoresin extract containing 30 mg of lycopene (n = 15) or no supplementation (n = 11) for 3 weeks before radical prostatectomy. Biomarkers of cell proliferation and apoptosis were assessed by Western blot analysis in benign and cancerous prostate tissues. Oxidative stress was assessed by measuring the peripheral blood lymphocyte DNA oxidation product 5-hydroxymethyl-deoxyuridine (5-OH-mdU). Usual dietary intake of nutrients was assessed by a food frequency questionnaire at baseline. Prostatectomy specimens were evaluated for pathologic stage, Gleason score, volume of cancer, and extent of high-grade prostatic intraepithelial neoplasia. Plasma levels of lycopene, insulin-like growth factor-1, insulin-like growth factor binding protein-3, and prostate-specific antigen were measured at baseline and after 3 weeks of supplementation or observation. After intervention, subjects in the intervention group had smaller tumors (80% vs 45%, less than 4 ml), less involvement of surgical margins and/or extra-prostatic tissues with cancer (73% vs 18%, organ-confined disease), and less diffuse involvement of the prostate by high-grade prostatic intraepithelial neoplasia (33% vs 0%, focal involvement) compared with subjects in the control group. Mean plasma prostate-specific antigen levels were lower in the intervention group compared with the control group. This pilot study suggests that lycopene may have beneficial effects in prostate cancer. Larger clinical trials are warranted to investigate the potential preventive and/or therapeutic role of lycopene in prostate cancer.
  
  
• #755
  Hadley CW, Miller EC, Schwartz SJ, Clinton SK.
  Department of Food Science and Technology, Division of Hematology and Oncology, The James Cancer Hospital and Solove Research Institute, The Ohio State University, 320 W. 10th Avenue, Columbus, OH 43210, USA.
  Tomatoes, lycopene, and prostate cancer: progress and promise.
  Exp Biol Med (Maywood) 2002 Nov;227(10):869-80
  Prostate cancer has emerged as a major public health problem in nations that have an affluent culture with an aging population. The search for etiologic risk factors and an emphasis on the development of chemopreventive agents has gained momentum over the last decade. Among the landmark epidemiologic findings during this period has been the association between the consumption of tomato products and a lower risk of prostate cancer. The traditional reductionist scientific approach has led many investigators to propose that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Thus, many laboratory and clinical studies are now underway with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate and other malignancies. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound could possibly reduce prostate cancer risk. In contrast to the pharmacologic approach with pure lycopene, many nutritional scientists direct their attention upon the diverse array of tomato products as a complex mixture of biologically active phytochemicals that together may have anti-prostate cancer benefits beyond those of any single constituent. These contrasting approaches will continue to be explored in clinical, laboratory and epidemiologic studies in the near future, providing hope that the next generation will benefit from this knowledge and experience a lower risk of prostate cancer.
  
  
• #758
  Giovannucci E.
  Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 1812 Longwood Avenue, Boston, MA 02115, USA.
  Edward.giovannucci@channing.harvard.edu
  A review of epidemiologic studies of tomatoes, lycopene, and prostate cancer.
  Exp Biol Med (Maywood) 2002 Nov;227(10):852-9
  Prostate cancer is the most common cancer in American men. Preventable measures for this malignancy are not well established. Among potentially beneficial natural compounds is the carotenoid lycopene, which is derived largely from tomato-based products. Recent epidemiologic studies have suggested a potential benefit of this carotenoid against the risk of prostate cancer, particularly the more lethal forms of this cancer. Five studies support a 30% to 40% reduction in risk associated with high tomato or lycopene consumption, three are consistent with a 30% reduction in risk, but the results were not statistically significant, and seven were not supportive of an association. The largest relevant dietary study, a prospective study in male health professionals found that consumption of two to four servings of tomato sauce per week was associated with about a 35% risk reduction of total prostate cancer and a 50% reduction of advanced (extraprostatic) prostate cancer. Tomato sauce was by far the strongest predictor of plasma lycopene levels in this study. In the largest plasma-based study, very similar risk reductions were observed for total and advanced prostate cancer for the highest versus lowest quintile of lycopene. Other studies, mostly dietary case-control studies, have not been as supportive of this hypothesis. The reasons for these inconsistencies are unclear, but in three of the seven null studies, tomato consumption or serum lycopene level may have been too low to observe an effect. Because the concentration and bioavailability of lycopene vary greatly across the various food items, dietary questionnaires vary markedly in their usefulness of estimating the true variation in tissue lycopene concentrations across individuals. To optimize the interpretation of future findings, the usefulness of the questionnaire to measure lycopene levels in a population should be directly assessed. Although not definitive, the available data suggest that increased consumption of tomatoes and tomato-based products may be prudent.
  
  
• #768
  Fleshner N, Agarwal S, Rao V.
  University of Toronto, Ontario, Canada.
  Serum and tissue lycopene and biomarkers of oxidation in prostate cancer patients: a case control study.
  Prostate Cancer Prostatic Dis 2000 Dec;3(S1):S13
  
  
• #774
  Pathak SK, Sharma RA, Mellon JK.
  Cancer Biomarkers and Prevention Group, Department of Oncology, University of Leicester, Leicester, LE2 7LX, UK.
  Chemoprevention of prostate cancer by diet-derived antioxidant agents and hormonal manipulation (Review).
  Int J Oncol 2003 Jan;22(1):5-13
  Cancer of the prostate is the most commonly diagnosed solid malignancy and the second leading cause of cancer-related death in men living in developed countries. With an ageing population, the number of men living with early stages of prostate cancer is expected to increase. There is an increasing need to prevent the onset of cancer or delay the progression of carcinogenesis in this organ. Chemoprevention is the administration of pharmacological agents to prevent, delay or reverse carcinogenesis. An example is the reversal of high grade intraepithelial neoplasia by hormonal manipulation using anti-oestrogens in breast carcinogenesis or anti-androgens in prostate carcinogenesis. Epidemiological data showing ethnic and geographic variations in the incidence of, and mortality from, prostate cancer have suggested that the consumption of certain dietary factors, particularly anti-oxidants, may be protective. These factors include the vitamins D and E, soy, lycopene and selenium. The administration of 5-alpha reductase inhibitors to patients with benign prostatic hyperplasia may also constitute a potentially chemopreventive intervention. The efficacy of chemopreventive agents needs to be investigated in randomised, placebo-controlled trials in suitable cohorts of high-risk individuals. In parallel, reliable assays of potential biomarkers of the efficacy of intervention need to be developed and validated rigorously.
  
  
• #777
  Kucuk O.
  Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA. kucuko@karmanos.org
  Chemoprevention of prostate cancer.
  Cancer Metastasis Rev 2002;21(2):111-24
  Chemoprevention is prevention of cancer by administering natural or synthetic chemicals. Anti-androgens are among the promising chemopreventive agents for prostate cancer because prostate epithelium is androgen dependent. A National Cancer Institute supported large, randomized, clinical prostate cancer chemoprevention trial has been conducted to test the efficacy of finasteride, an inhibitor of 5-a-reductase, which converts testosterone to 5-hydroxy-testosterone. Now the focus is on micronutrients and phytochemicals, which have potential preventive effects against prostate cancer. Lycopene, soy isoflavones, vitamin E and selenium are among the most promising nutritional chemopreventive agents. Another NCI supported large clinical chemoprevention trial was recently started to investigate the efficacy of selenium and vitamin E, alone or in combination in the prevention of prostate cancer. Inclusion of appropriate biomarkers in clinical trials will help elucidate the mechanisms by which genetic and epigenetic pathways of carcinogenesis are modulated by nutrients and phytochemicals.
  
  
• #779
  Minorsky PV.
  Department of Natural Sciences, Mercy College, Dobbs Ferry, NY 10522, USA.
  Lycopene and the prevention of prostate cancer: the love apple lives up to its name.
  Plant Physiol 2002 Nov;130(3):1077
  
  
• #791
  Huang HY, Alberg AJ, Norkus EP, Hoffman SC, Comstock GW, Helzlsouer KJ.
  Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.
  Prospective study of antioxidant micronutrients in the blood and the risk of developing prostate cancer.
  Am J Epidemiol 2003 Feb 15;157(4):335-44
  Antioxidant micronutrients may have chemopreventive effects. The authors examined the associations between prediagnostic blood levels of micronutrients and prostate cancer risk in two nested case-control studies of 9,804 and 10,456 male residents of Washington County, Maryland, who donated blood in 1974 (CLUE I) and 1989 (CLUE II), respectively. Until 1996, 182 men for whom adequate serum remained for assays in the CLUE I cohort and 142 men in the CLUE II cohort developed prostate cancer. Each case was matched with two controls by age, gender, race, and date of blood donation. In both cohorts, cases and controls had similar concentrations of alpha-carotene, beta-carotene, total carotene, beta-cryptoxanthin, lutein, lycopene, retinol, and ascorbic acid; serum alpha-tocopherol was weakly associated with prostate cancer risk. Higher retinyl palmitate concentrations were associated with a lower risk in CLUE I but not CLUE II. In CLUE I, cases had lower concentrations of gamma-tocopherol than did controls (p = 0.02), but no dose-response trend was observed. A strong inverse association between gamma-tocopherol and prostate cancer risk was observed in CLUE II. Findings do not replicate previous reports of a protective association between lycopene and prostate cancer, but they suggest potential chemopreventive effects of gamma-tocopherol on prostate cancer.
  
  
• #796
  Kim L, Rao AV, Rao LG.
  Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada.
  Effect of Lycopene on Prostate LNCaP Cancer Cells in Culture.
  J Med Food 2002 Winter;5(4):181-7
  Epidemiological studies have shown an inverse relationship between serum lycopene levels and the risk of prostate cancer. The objective of this study was to measure the effect of lycopene on the proliferation of LNCaP human prostate cancer cells in culture. A new, water-dispersible lycopene in an appropriate vehicle was used. The stock solution was diluted in the medium to obtain lycopene concentrations of 10(-6), 10(-5), and 10(-4) M; their corresponding vehicles were similarly diluted to be used as controls. Cells were grown for 48 hours in RPMI-1640 medium supplemented with 10% fetal bovine serum and antibiotics. Lycopene was then added at different concentrations, and the cells were allowed to grow for 24, 48, 72, and 96 hours. Lycopene at concentrations of 10(-6) and 10(-5) M significantly reduced the growth of LNCaP cells after 48, 72, and 96 hours of incubation, by 24.4% to 42.8% (P <.05). The inhibitory effect of lycopene was significantly higher than that of the corresponding vehicle controls. In a follow-up experiment, a lower range of lycopene concentrations (10(-9) to 10(-7) M) was used to determine whether there was a dose-response effect. Lycopene significantly decreased the growth of cells in a dose-dependent manner when cells were incubated for 24, 48, 72, or 96 hours (F = 3.150, 11.27, 54.51, and 297.5, respectively; P <.05). The growth inhibitory effect of lycopene on human prostate cancer cells observed in this study suggests a possibly important role for lycopene as an antioxidant in human prostate cancer; however, investigations of other mechanisms are warranted.
  
  
• #798
  Willis MS, Wians FH.
  Department of Pathology, The University of Texas Southwestern Medical Center, Dallas, TX, USA
  The role of nutrition in preventing prostate cancer: a review of the proposed mechanism of action of various dietary substances.
  Clin Chim Acta 2003 Apr;330(1-2):57-83
  BACKGROUND: Dietary modifications to prevent prostate cancer (PCa) continue to gain attention as research demonstrates that various dietary nutrients/supplements are related to decreased risk of developing prostate cancer (PCa). Several studies have focused on the antioxidant and nonantioxidant effects of various dietary substances in the prevention of PCa. Research into the mechanisms by which PCa is prevented, or its disease severity is reduced by dietary micronutrients and vitamins continues to enrich our understanding of the mechanisms by which PCa is initiated and progresses. METHODS: We reviewed the literature on dietary nutrients with antioxidant properties that have been shown to have a positive effect in reducing the incidence or preventing the occurrence of PCa including carotenoids (e.g., lycopene), retinoids (e.g., vitamin A), vitamin E, vitamin C, selenium, and polyphenols. Other nutrients examined included vitamin D and calcium. RESULTS: Many dietary micronutrients have demonstrated significant and complex effects on PCa cell proliferation, differentiation, and signaling related to the initiation, progression, and regression of PCa. CONCLUSION: Understanding the mechanisms by which various dietary nutrients exert their effects on PCa may make it possible to design effective drugs for treating PCa and to promote better nutrition and lifestyle changes in those at risk for PCa.
  
  
• #802
  Oh WK, Small EJ.
  Lank Center for Genitourinary Oncology, Department of Adult Oncology, Dana-Farber Cancer Institute and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA.
  Complementary and alternative therapies in prostate cancer.
  Semin Oncol 2002 Dec;29(6):575-84
  Complementary and alternative therapies are used with increasing frequency in men with prostate cancer. However, little is known about the efficacy of such therapies for this cancer. While epidemiological data support the association between intake of certain micronutrients with development of prostate cancer, there exist limited prospective data that support the chemopreventative or therapeutic value of such nutritional agents in prostate cancer. To date, one of the most studied treatments has been PC-SPES, a combination of eight herbal therapies with activity against prostate cancer. Studies in cell lines of human prostate cancer demonstrate significant dose-dependent decreases in cellular viability after exposure to extracts of this agent. Clinical studies suggested that PC-SPES could reduce prostate specific antigen levels in patients with either androgen-dependent or androgen-independent prostate cancer. Toxicity was mild, although there was a low risk of thromboembolic events with such treatment. Manufacture of PC-SPES was recently halted, after revelations that the herbal combination was contaminated with warfarin, which led to a recall by the manufacturer. Subsequent analyses also revealed the presence of diethylstilbestrol (DES) and indomethacin in some lots of PC-SPES. Available data regarding other alternative therapies are reviewed as well.
  
  
• #827
  Pohar KS, Gong MC, Bahnson R, Miller EC, Clinton SK.
  Division of Urology, Department of Surgery, Ohio State University College of Medicine and Public Health, 4841 UHC, 456 West 10th Avenue, OH 43210, Columbus, USA, pohar-1@medctr.osu.edu
  Tomatoes, lycopene and prostate cancer: a clinician's guide for counseling those at risk for prostate cancer.
  World J Urol. 2003 May;21(1):9-14. Epub 2003 Mar 22.
  Prostate cancer has become a major public health issue and the search for etiologic risk factors and the development of chemopreventive agents has gained momentum over the last decade. An important epidemiologic finding has been the association between the consumption of tomato products and a lower risk of prostate cancer. Several investigators have proposed that lycopene, a carotenoid consumed largely from tomato products, may be the component responsible for lowering the risk of prostate cancer. Laboratory and clinical studies have been initiated with the goal of assessing the ability of pure lycopene to serve as a chemopreventive agent for prostate cancer. The focus on lycopene should continue, and an improved understanding of lycopene absorption, distribution, role in antioxidant reactions, and metabolism is critical in the quest to elucidate mechanisms whereby this compound may possibly reduce prostate cancer risk.
  
  
• #835
  Gallagher RP, Kutynec CL.
  Clinical Professor, Department of Health Care and Epidemiology, Faculty of Medicine, University of British Columbia, Vancouver, British Columbia.
  Diet, micronutrients and prostate cancer: a review of the evidence.
  Can J Urol. 1997 Jun;4(2 Supp 1):22-27.
  Prostate cancer is the most common life threatening cancer in males in Canada, however, relatively little is known about it etiology. Recent popular interest has focused on the role of diet. Information from a series of 13 analytic studies suggests that risk of the disease is positively related to intake of dietary fat. Furthermore, the relationship between fat consumption and prostate cancers of aggressive behavior appears to be stronger than that seen for all prostate cancers combined. Evidence from studies examining the relationship of beta-carotene and Vitamin A to prostate cancer is ambiguous with some investigations showing a direct association with risk and others showing no association. More recently, several studies have shown an inverse association between tomato products or lycopene consumption and prostate cancer. As well, indirect evidence suggests that consumption of soy based products (such as tofu) contains genistein and other isoflavones which may decrease risk of prostate cancer. Insufficient evidence is available on the relationship of prostate cancer to either lycopene or genistein to make dietary recommendations to prostate cancer patients or the general population. More research is urgently needed on the topic of dietary correlate of prostate cancer.
  
  
• #836
  Boyle P, Severi G, Giles GG.
  Division of Epidemiology and Biostatistics, European Institute of Oncology, Via
  Ripamonti 435, 20141 Milan, Italy. director.epi@ieo.it
  The epidemiology of prostate cancer.
  Urol Clin North Am. 2003 May;30(2):209-17.
  The etiology of prostate cancer remains virtually unknown. Although there are a number of new leads with regard to risk factors for prostate cancer, more research is required to confirm them. There is little purpose in conducting further case-control studies of prostate cancer-particularly since the use of PSA testing has become wide-spread. Instead, future epidemiologic studies should focus on prostate tumor subclassification, in terms of method of detection, markers of biological "aggressiveness," and genetic changes. Many of these new leads involve the possible influence of polymorphisms in key genes involved in important physiologic processes in the prostate. To fully explore the complexity of interrelationships between the several elements in these pathways will require large cohort studies in which blood is sampled prior to diagnosis. Such studies will be important for identifying which modifiable aspects of lifestyle (such as diet, alcohol, tobacco, physical activity) might be targeted for intervention, to reduce risk. The detection of early prostate cancers by PSA testing relatives of men with prostate cancer has affected t