A randomized trial of lycopene supplementation in Tobago men with high prostate cancer risk. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. Tea and lycopene protect against prostate cancer. Lycopene as a chemopreventive agent in the treatment of high-grade prostate intraepithelial neoplasia. The association between baseline vitamin E, selenium, and prostate cancer in the alpha-tocopherol, beta-carotene cancer prevention study. Risk factors for lung cancer and for intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. Predictors of serum selenium in cigarette smokers and the lack of association with lung and prostate cancer risk. A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet. Association of energy and fat intake with prostate carcinoma risk: results from The Netherlands Cohort Study.
This unblinded, randomized, Phase I clinical trial was conducted to determine whether lycopene supplementation lowered serum prostate specific antigen (PSA), surrogate endpoint for prostate cancer initiation or progression, in men with elevated prostate cancer risk. Afro-Caribbean men (n=81) with high-grade prostatic intraepithelial neoplasia, atypical foci or repeated non-cancerous biopsies, ascertained in a population-based screening program, were randomized to four months intervention with 30 mg/day lycopene (Lyc-O-Mato) plus a multivitamin, or to multivitamin, only. Serum PSA and lycopene were compared at randomization, 1, and 4 mo using two-sided chi2 and t-tests for independent samples. Treatment groups were similar at baseline. Serum lycopene levels approximately doubled in the lycopene intervention group. Serum PSA declined during the first month of treatment, but returned to randomization level by month 4. The PSA response was nearly identical in both treatment groups. No adverse effects attributed to lycopene supplementation were documented. We conclude that the PSA lowering response to antioxidant supplementation observed in previous 3-wk studies in men awaiting prostatectomy may have been a transient response, perhaps not specific to lycopene. Lowering of serum PSA may not be an appropriate endpoint for the long-term studies needed to evaluate lycopene supplementation for reducing prostate cancer initiation or progression. Lycopene is a promising nutritional component for chemoprevention of prostate cancer (PCa). A possibly beneficial role of lycopene in patients diagnosed with benign prostate hyperplasia (BPH), who are at increased risk of developing PCa, has been suggested, although clinical data are lacking. Therefore, this pilot study aimed to investigate the effects of lycopene supplementation in elderly men diagnosed with BPH. A total of 40 patients with histologically proven BPH free of PCa were randomized to receive either lycopene at a dose of 15 mg/d or placebo for 6 mo. The effects of the intervention on carotenoid status, clinical diagnostic markers of prostate proliferation, and symptoms of the disease were assessed. The primary endpoint of the study was the inhibition or reduction of increased serum prostate-specific antigen (PSA) levels. The 6-mo lycopene supplementation decreased PSA levels in men (P < 0.05), whereas there was no change in the placebo group. The plasma lycopene concentration increased in the group taking lycopene (P < 0.0001) but other plasma carotenoids were not affected. Whereas progression of prostate enlargement occurred in the placebo group as assessed by trans-rectal ultrasonography (P < 0.05) and digital rectal examination (P < 0.01), the prostate did not enlarge in the lycopene group. Symptoms of the disease, as assessed via the International Prostate Symptom Score questionnaire, were improved in both groups with a significantly greater effect in men taking lycopene supplements. In conclusion, lycopene inhibited progression of BPH. Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. Its long latency and geographical variation suggest the possibility of prevention or postponement of onset by dietary modification. To investigate the possible joint effect of lycopene and green tea on prostate cancer risk, a case-control study was conducted in Hangzhou, China, with 130 prostate cancer patients and 274 hospital controls. Information on tea and dietary intakes, and possible confounders was collected using a structured questionnaire. The risk of prostate cancer for the intake of tea and lycopene and their joint effect were assessed using multivariate logistic regression models. Prostate cancer risk was reduced with increased consumption of green tea. The protective effect of green tea was significant (odds ratio 0.14, 95% CI: 0.06-0.35) for the highest quartile relative to the lowest after adjusting for total vegetables and fruits intakes and other potential confounding factors. Intakes of vegetables and fruits rich in lycopene were also inversely associated with prostate cancer risk (odds ratio 0.18, 95% CI 0.08-0.39). Interaction analysis showed that the protective effect from tea and lycopene consumption was synergistic (p<0.01). This study suggests that habitual drinking tea and intakes of vegetables and fruits rich in lycopene could lead to a reduced risk of prostate cancer in Chinese men. Together they have a stronger preventive effect than either component taken separately. This is the first epidemiological study to investigate the joint effect between tea drinking and lycopene intake. Because of its long latency, slow growing nature, and high prevalence, prostate cancer is the best model for chemoprevention. High-grade prostate intraepithelial neoplasia (HGPIN) is a precursor of prostate cancer. Chemoprevention with lycopene has shown definite results in prostate cancer. We undertook a study to use lycopene as a chemopreventive agent in the treatment of HGPIN for preventing prostate cancer from developing in this vulnerable group of patients.
                A total of 40 patients with HGPIN were randomized into 2 groups: one received 4 mg lycopene twice a day for one year, and the other was periodically followed up. Total follow-up was one year.
                Our results show that lycopene can delay or prevent HGPIN from developing into occult prostate cancer, and there exists an inverse relationship between lycopene and prostate-specific antigen. Being a vegetable carotenoid, lycopene is a safe drug to be used for a longer period without any adverse reaction.
                Lycopene is an effective chemopreventive agent in the treatment of HGPIN, with no toxicity and good patient tolerance. The association between prostate cancer and baseline vitamin E and selenium was evaluated in the trial-based cohort of the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (n = 29,133). During up to 9 years of follow-up, 317 men developed incident prostate cancer. Multivariate Cox proportional hazards models that adjusted for intervention group, benign prostatic hyperplasia, age, smoking, and urban residence were used to evaluate associations between prostate cancer and exposures of interest. There were no significant associations between baseline serum alpha-tocopherol, dietary vitamin E, or selenium and prostate cancer overall. The associations between prostate cancer and vitamin E and some of the baseline dietary tocopherols differed significantly by alpha-tocopherol intervention status, with the suggestion of a protective effect for total vitamin E among those who received the alpha-tocopherol intervention (relative risk was 1.00, 0.68, 0.80, and 0.52 for increasing quartiles; P = 0.07). Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality.
                We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention.
                CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests.
                According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations.
                CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland. Epidemiological studies have suggested that low levels of selenium are associated with a higher incidence of both lung and prostate cancer. We analyzed the selenium serum concentration in 356 Carotene and Retinol Efficacy Trial (CARET) participants who later developed lung cancer and 356 matched controls and in 235 prostate cancer cases and 456 matched controls. Serum samples were obtained a mean of 4.7 years before diagnosis for both tumor types. Controls were matched to cases by year of randomization, age, smoking status, treatment arm, exposure population (asbestos workers or cigarette smokers), and year of blood draw. In the control population (n = 820), significant predictors of low serum selenium concentration were current smoking status and East Coast locations of the study center. Overall, there was no significant difference in mean serum selenium in lung cancer cases versus controls (11.91 microg/dl versus 11.77 microg/dl) or prostate cancer cases versus controls (11.48 microg/dl versus 11.43 microg/dl). No statistically significant trend in odds ratio was seen across quartiles of serum selenium for lung cancer (P = 0.49) or prostate cancer (P = 0.69). In a subpopulation of 174 prostate cancer patients who had clinical and pathological staging material reviewed, there was no association between serum selenium and Gleason score or clinical or pathological stage. In the CARET population of current and former smokers consuming an ad libitum diet, the serum concentration of selenium was not a risk factor for either lung cancer or prostate cancer. The age-adjusted incidence of prostate cancer is low in Japan, and it has been suggested that the traditional Japanese diet, which includes many soy products, plays a preventive role against prostate cancer. We performed a case-control study on dietary factors and prostate cancer in order to assess the hypothesis that the traditional Japanese diet reduces the risk of prostate cancer. Four geographical areas (Ibaraki, Fukuoka, Nara, and Hokkaido) of Japan were selected for the survey. Average daily intake of food from 5 years before the diagnosis was measured by means of a semi-quantitative food frequency questionnaire. We studied 140 cases and 140 individually age ( +/- 5 years)-matched hospital controls for analysis. Estimates of age-adjusted odds ratios (ORs) and linear trends were calculated by conditional logistic regression models with adjustment for cigarette smoking and total energy intake as confounding factors. Consumption of fish, all soybean products, tofu (bean curds), and natto (fermented soybeans) was associated with decreased risk. ORs of the fourth vs. first quartile and 95% confidence intervals (95%CIs) were 0.45 (0.20-1.02) for fish, 0.53 (0.24-1.14) for all soybean products, 0.47 (0.20-1.08) for tofu, and 0.25 (0.05-1.24) for natto. Consumption of fish and natto showed significantly decreasing linear trends for risk (P < 0.05). Consumption of meat was significantly associated with increased risk (the OR of the second vs. first quartile was 2.19, 95%CI 1.00-4.81). Consumption of milk, fruits, all vegetables, green-yellow vegetables, and tomatoes showed no association. Our results provide support to the hypothesis that the traditional Japanese diet, which is rich in soybean products and fish, might be protective against prostate cancer. The roles of energy and fat intake as risk factors for prostate carcinoma are still questionable. Therefore, these factors were evaluated in the Netherlands Cohort Study described in this article.
                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. Intake of energy, fat, and separate fatty acids were measured by means of a self-administered questionnaire; fat intake was adjusted for energy by regression analysis. The case-cohort method was used to calculate rate ratios (RRs). Analyses were conducted for all prostate carcinoma cases together as well as for case subgroups (latent vs. nonlatent and localized vs. advanced).
                No associations were found in multivariate analyses between prostate carcinoma and intake of energy, total fat, total saturated fatty acids, or total trans unsaturated fatty acids (RR highest vs. lowest quintile: 0.99, 1.10, 1.19, and 0.99, respectively). Oleic acid intake showed a nonsignificant positive association (RR = 1.38, 95% CI: 0.88-2.19). Positive associations were also observed for intake of oleic acid in subgroup analyses. Linoleic (RR = 0.78, 95% CI: 0. 56-1.09) and linolenic (RR = 0.76, 95% CI: 0.66-1.04) acid intake were associated with nonsignificantly decreased risks; only for linolenic acid did these associations persist in subgroup analyses. No associations were found for intake of arachidonic acid, eicosapentaenoic acid, or docosahexaenoic acid.
                These data suggest that certain fatty acids might be involved in prostate carcinoma occurrence, although the possibility that these were chance findings cannot be ruled out.
                Copyright 1999 American Cancer Society.
Given that only three RCTs were included in this systematic review, and the high risk of bias in two of the three studies, there is insufficient evidence to either support, or refute, the use of lycopene for the prevention of prostate cancer. Similarly, there is no robust evidence from RCTs to identify the impact of lycopene consumption upon the incidence of prostate cancer, prostate symptoms, PSA levels or adverse events.