A prospective cohort study on antioxidant and folate intake and male lung cancer risk.

Many studies have reported inverse associations between vegetable and fruit consumption and lung cancer risk. The aim of the present study was to elucidate the role of several antioxidants and folate in this relationship. In the Netherlands Cohort Study on Diet and Cancer, 58,279 men of ages 55-69 years at baseline in 1986 returned a questionnaire including a 150-item food frequency questionnaire. After 6.3 years of follow-up, 939 male lung cancer cases were registered. A new Dutch carotenoid database was used to estimate intake of alpha-carotene, beta-carotene, lutein + zeaxanthin, beta-cryptoxanthin, and lycopene, completed with the antioxidant vitamins C and E and folate. Using case-cohort analysis, rate ratios were calculated, adjusted for age, smoking, educational level, and family history of lung cancer. Protective effects on lung cancer incidence were found for lutein + zeaxanthin, beta-cryptoxanthin, folate, and vitamin C. Other carotenoids (alpha-carotene, beta-carotene, and lycopene) and vitamin E did not show significant associations. After adjustment for vitamin C, only folate remained inversely associated, and after adjustment for folate, only beta-cryptoxanthin and vitamin C remained significantly associated. Inverse associations were strongest among current smokers and weaker for former smokers at baseline. Inverse associations with carotenes, lutein + zeaxanthin, and beta-cryptoxanthin seemed to be limited to small cell and squamous cell carcinomas. Only folate and vitamin C intake appeared to be inversely related to small cell and squamous cell carcinomas and adenocarcinomas. Folate, vitamin C, and beta-cryptoxanthin might be better protective agents against lung cancer in smokers than alpha-carotene, beta-carotene, lutein + zeaxanthin, and lycopene.     

Dietary carotenoids and risk of lung cancer in a pooled analysis of seven cohort studies.

Intervention trials with supplemental beta-carotene have observed either no effect or a harmful effect on lung cancer risk. Because food composition databases for specific carotenoids have only become available recently, epidemiological evidence relating usual dietary levels of these carotenoids with lung cancer risk is limited. We analyzed the association between lung cancer risk and intakes of specific carotenoids using the primary data from seven cohort studies in North America and Europe. Carotenoid intakes were estimated from dietary questionnaires administered at baseline in each study. We calculated study-specific multivariate relative risks (RRs) and combined these using a random-effects model. The multivariate models included smoking history and other potential risk factors. During follow-up of up to 7-16 years across studies, 3,155 incident lung cancer cases were diagnosed among 399,765 participants. beta-Carotene intake was not associated with lung cancer risk (pooled multivariate RR = 0.98; 95% confidence interval, 0.87-1.11; highest versus lowest quintile). The RRs for alpha-carotene, lutein/zeaxanthin, and lycopene were also close to unity. beta-Cryptoxanthin intake was inversely associated with lung cancer risk (RR = 0.76; 95% confidence interval, 0.67-0.86; highest versus lowest quintile). These results did not change after adjustment for intakes of vitamin C (with or without supplements), folate (with or without supplements), and other carotenoids and multivitamin use. The associations generally were similar among never, past, or current smokers and by histological type. Although smoking is the strongest risk factor for lung cancer, greater intake of foods high in beta-cryptoxanthin, such as citrus fruit, may modestly lower the risk.     

Intakes of fruits and vegetables,carotenoids and vitamins A,E, C in relation to the risk of bladder cancer in the ATBC cohort study

We examined the relation between dietary fruit and vegetables, carotenoids and vitamin intakes and the risk of bladder cancer among male smokers in a prospective cohort study. Over a median of 11 years, we followed 27 111 male smokers aged 50-69 years who were initially enrolled in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study. During this period, 344 men developed bladder cancer. All of these men had completed a 276-food item dietary questionnaire at baseline. Cox proportional hazards models were used to estimate the relative risks and 95% confidence intervals and to simultaneously adjust for age, smoking history, energy intake and intervention group. Consumption of fruits and vegetables was not associated with the risk of bladder cancer (relative risk=1.28; 95% confidence intervals CI: 0.89-1.84, for highest vs lowest quintile). Similarly, no associations were observed for groups of fruits or vegetables (berries and cruciferous vegetables), or for specific fruits and vegetables. Dietary intakes of alpha-carotene, beta-carotene, lycopene, lutein/zeaxanthin, beta-cryptoxanthin, vitamins A, E, and C, and folate were not related to the risk of bladder cancer. These findings suggest that fruit and vegetable intakes are not likely to be associated with bladder cancer risk. However, these results may not be generalisable to non-smokers.     

Plasma and dietary carotenoids are associated with reduced oxidative stress in women previously treated for breast cancer.

Dietary carotenoids show numerous biological activities, including antioxidant activity, induction of apoptosis, and inhibition of mammary cell proliferation. Studies examining the role of carotenoid consumption in relation to breast cancer recurrence are limited and report mixed results. We tested the hypothesis that breast cancer survivors with high dietary and plasma carotenoids would show significantly lower levels of oxidative stress than breast cancer survivors with low dietary and plasma carotenoid levels. Two hundred seven postmenopausal breast cancer survivors from the Women's Healthy Eating and Living Study volunteered for this ancillary study. Dietary data were analyzed by the Arizona Food Frequency Questionnaire and plasma carotenoids alpha-carotene, beta-carotene, lutein plus zeaxanthin, lycopene, and beta-cryptoxanthin and quantified with high-performance liquid chromatography, and immunoaffinity chromatography-monoclonal antibody-based ELISAs were used to analyze the urine samples for 8-hydroxy-2'-deoxyguanosine (8-OhdG) and 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha). The correlations between dietary and plasma carotenoids were 0.34 for beta-carotene, 0.46 for alpha-carotene, 0.39 for beta-cryptoxanthin, 0.27 for lycopene, 0.30 for lutein plus zeaxanthin, and 0.30 for total carotenoids. The 8-OHdG oxidative stress biomarker was significantly reduced at the highest quartile of total plasma carotenoid concentrations (P = 0.001) and 8-iso-PGF2alpha was moderately reduced (P = 0.088). Dietary carotenoid levels were not significantly associated with oxidative, stress indicators, although dietary lycopene and lutein/zeaxanthin were modestly associated with 8-OHdG levels (P = 0.054 and 0.088, respectively). Key findings include a significant inverse association between total plasma carotenoid concentrations and oxidative stress as measured by urinary 8-OHdG and a moderately significant inverse association with 8-iso-PGF2alpha, a protective association that was not shown for dietary carotenoid intake.     

Carotenoid Intake and Esophageal Cancer Risk: a Meta-analysis

This meta-analysis was conducted to evaluate the association between intake of carotenoids and risk ofesophageal cancer. A systematic search using PubMed, Cochrane Library, Web of Science, Scopus, CNKI, andCBM (updated to 6 May 2012) identified ten articles meeting the inclusion criteria with 1,958 cases of esophagealcancer and 4,529 controls. Higher intake of beta-carotene, alpha-carotene, lycopene, beta-cryptoxanthin, lutein,and zeaxanthin reduced esophageal cancer risk with pooled ORs of 0.58 (95% CI 0.44, 0.77), 0.81 (95% CI 0.70,0.94), 0.75 (95% CI 0.64, 0.86), 0.80 (95% CI 0.66, 0.97), and 0.71 (95% CI 0.59, 0.87), respectively. In subgroupanalyses, beta-carotene showed protective effects against esophageal adenocarcinoma in studies located in Europeand North America. Alpha-carotene, lycopene, and beta-cryptoxanthin showed protection against esophagealsquamous cell cancer. This meta-analysis suggested that higher intake of carotenoids (beta-carotene, alphacarotene,lycopene, beta-cryptoxanthin, lutein, and zeaxanthin) is associated with lower risk of esophageal cancer.Further research with large-sample studies need to be conducted to better clarify the potentially protectivemechanisms of carotenoid associations risk of different types of esophageal cancer.     

Prediagnostic levels of serum beta-cryptoxanthin and retinol predict smoking-related lung cancer risk in Shanghai, China.

Higher blood levels of beta-carotene have been found to be associated with reduced risk of lung cancer, but large intervention trials have failed to demonstrate reduced lung cancer incidence after prolonged high-dose beta-carotene supplementation. Data on blood levels of specific carotenoids other than beta-carotene in relation to lung cancer are scarce. Little is known about the relationship between prediagnostic serum levels of carotenoids, retinol, and tocopherols, and risk of lung cancer especially in non-Western populations. Between January 1986 and September 1989, 18,244 men ages 45-64 years participated in a prospective study of diet and cancer in Shanghai, China. Information on tobacco smoking and other lifestyle factors was obtained through in-person interviews. A serum sample was collected from each study participant at baseline. During the first 12 years of follow-up, 209 lung cancer cases, excluding those diagnosed within 2 years of enrollment, were identified. For each cancer case, three cancer-free control subjects were randomly selected from the cohort and matched to the index case by age (within 2 years), month and year of blood sample collection, and neighborhood of residence. Serum concentrations of retinol, alpha- and gamma-tocopherols, and specific carotenoids including alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were determined on the 209 cases and 622 matched controls by high-performance liquid chromatography methods. A high prediagnostic serum level of beta-cryptoxanthin was significantly associated with reduced risk of lung cancer; relative to the lowest quartile, the smoking-adjusted relative risks (95% confidence intervals) for the 2nd, 3rd, and 4th quartile categories were 0.72 (0.41-1.26), 0.42 (0.21-0.84), and 0.45 (0.22-0.92), respectively (P for trend = 0.02). Increased serum levels of other specific carotenoids including alpha-carotene, beta-carotene, lycopene, and lutein/zeaxanthin were related to reduced risk of lung cancer although the inverse associations were no longer statistically significant after adjustment for smoking. A statistically significant 37% reduction in risk of lung cancer was noted in smokers with above versus below median level of total carotenoids. Serum retinol levels showed a threshold effect on lung cancer risk. Compared with the lowest quartile (<40 microg/dl), the smoking-adjusted relative risk (95% confidence interval) was 0.60 (0.39-0.92) for men in the 2nd-4th quartiles of retinol values combined; no additional decrease in risk was observed between individuals from the 2nd to 4th quartiles. There were no associations between prediagnostic serum levels of alpha- and gamma-tocopherols and lung cancer (all Ps for trend > or =0.4). The present data indicate that higher prediagnostic serum levels of total carotenoids and beta-cryptoxanthin were associated with lower smoking-related lung cancer risk in middle-aged and older men in Shanghai, China. Low level of serum retinol (with a threshold effect) is associated with increased lung cancer risk in this oriental population.     

Prospective study of vitamins C, E, and A and carotenoids and risk of oral premalignant lesions in men

Case-control studies indicate that vitamins C, E, A and carotenoids decrease risk of oral premalignant lesions (OPLs) and oral cancer, but clinical trials have failed to find protective effects of beta-carotene and suggest that vitamin E may increase risk. The authors prospectively evaluated the association between intake of vitamins C, E, A and carotenoids and incidence of OPL. Participants were 42,340 men in the Health Professionals Follow-up Study who provided information on supplement use and diet every 2-4 years by food frequency questionnaire. The authors confirmed 207 clinically or histopathologically diagnosed OPL events occurring between 1986 and 2002 by medical record review. Multivariate-adjusted relative risks (RR) of OPL were calculated with proportional hazards models. Total intake of vitamin C, vitamin A or carotenoids was not significantly associated with OPL risk. Dietary vitamin C was significantly associated with reduced risk (quintile 5 vs. 1, RR = 0.52, 95% CI 0.31-0.85, p(trend) = 0.04), but no association with supplemental vitamin C was observed. Inverse associations were apparent for beta-cryptoxanthin and alpha-carotene intake. No clear relationship emerged with beta-carotene, lycopene or lutein/zeaxanthin. Vitamin E was associated with increased risk (quintile 5 vs. 1, RR = 1.86, 95% CI 1.06-3.19), particularly among current smokers and with supplemental intake (current-smokers, supplement dose tertile 3 vs. 1, RR = 3.07, 95% CI 1.28-7.34, p(trend) = 0.01). For current smokers, beta-carotene also increased risk. Vitamin C from dietary sources, but not supplements, was associated with a reduced risk of OPL. The observed increased risk for current smokers with high vitamin E or beta-carotene intake should be explored further.     

Serum carotenoids and risk of cervical intraepithelial neoplasia in Southwestern American Indian women.

The objective of this research was to evaluate the association between serum carotenoids and cervical intraepithelial neoplasia (CIN) among Southwestern American Indian women. Cases were American Indian women with biopsy-proven CIN II/III cervical lesions (n = 81) diagnosed between November 1994 and October 1997. Controls were American Indian women from the same clinics with normal cervical epithelium (n = 160). All of the subjects underwent interviews and laboratory evaluations. Interviews evaluated demographic information, sexual history, and cigarette smoking. Serum concentrations of alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin were measured by high performance liquid chromatography. Cervical human papillomavirus infection was detected using a PCR-based test. Increasing levels of alpha-carotene, beta-cryptoxanthin, and lutein/zeaxanthin were associated with decreasing risk of CIN II/III. In addition, the highest tertiles of beta-cryptoxanthin (odds ratio = 0.39, 95% confidence interval = 0.17-0.91) and lutein/zeaxanthin (odds ratio = 0.40, 95% confidence interval = 0.17-0.95) were associated with the lowest risk of CIN. In conclusion, specially targeted intervention efforts to increase consumption of fruits and vegetables may protect Southwestern American Indian women from developing CIN.     

Differential Effects of Cigarette Smoking and Alcohol Consumption on the Plasma Levels of Carotenoids in Middle-aged Japanese Men

Although several studies have reported that cigarette smoking and alcohol consumption are inversely associated with the plasma level of beta-carotene even after adjustment for dietary carotene intake, their effects on other carotenoids have not been examined extensively. The authors examined the associations of smoking and alcohol with plasma levels of the five principal carotenoids (beta-carotene, alpha-carotene, lutein, lycopene, and zeaxanthin). The subjects were 634 apparently healthy men aged 40–49 years who were sampled randomly from five areas in Japan with varying rates of mortality from gastric cancer. Multiple linear regression analysis controlling for age, serum total cholesterol, serum triglycerides, body mass index, and consumption frequencies of green vegetables, yellow vegetables and fruit, showed that both smoking and alcohol had a significant inverse association with the plasma levels of beta-carotene and alpha-carotene; only smoking reduced the level of lutein, and neither smoking nor alcohol significantly affected the level of lycopene or zeaxanthin. With regard to the reduction of beta-carotene and alpha-carotene, the effect of smoking was smaller in drinkers than in nondrinkers, and the effect of alcohol was smaller in smokers than in nonsmokers, and significant interactions between smoking and alcohol were observed (P=0.034 for beta-carotene and 0.026 for alpha-carotene). The results indicate that the differential effects of smoking and alcohol should be considered when the health effects of plasma carotenoids are examined.     

Do dietary lycopene and other carotenoids protect against prostate cancer?

To determine whether dietary intake of lycopene and other carotenoids has an etiological association with prostate cancer, a case-control study was conducted in Hangzhou, southeast China during 2001-2002. The cases were 130 incident patients with histologically confirmed adenocarcinoma of the prostate. The controls were 274 hospital inpatients without prostate cancer or any other malignant diseases. Information on usual food consumption, including vegetables and fruits, was collected by face-to-face interviews using a structured food frequency questionnaire. The risks of prostate cancer for the intake of carotenoids and selected vegetables and fruits rich in carotenoids were assessed using multivariate logistic regression, adjusting for age, locality, education, income, body mass index, marital status, number of children, family history of prostate cancer, tea drinking, total fat and caloric intake. The prostate cancer risk declined with increasing consumption of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein and zeaxanthin. Intake of tomatoes, pumpkin, spinach, watermelon and citrus fruits were also inversely associated with the prostate cancer risk. The adjusted odds ratios for the highest versus the lowest quartiles of intake were 0.18 (95% CI: 0.08-0.41) for lycopene, 0.43 (95% CI: 0.21-0.85) for alpha-carotene, 0.34 (95% CI: 0.17-0.69) for beta-carotene, 0.15 (95% CI: 0.06-0.34) for beta-cryptoxanthin and 0.02 (95% CI: 0.01-0.10) for lutein and zeaxanthin. The corresponding dose-response relationships were also significant, suggesting that vegetables and fruits rich in lycopene and other carotenoids may be protective against prostate cancer.     

Serum carotenoids and vitamins and risk of cervical dysplasia from a case-control study in Japan

The relationships between risk of cervical dysplasia and dietary and serum carotenoids and vitamins were investigated in a case-control study. Cases were 156 women who attended Papanicolaou test screening in nine institutes affiliated with Japan Study Group of Human Papillomavirus (HPV) and Cervical Cancer and had cervical dysplasia newly histologically confirmed. Age-matched controls were selected from women with normal cervical cytology attending the same clinic. Blood sample and cervical exfoliated cells were obtained for measuring serum retinol, alpha-carotene, beta-carotene, zeaxanthin/lutein, cryptoxanthin, lycopene and alpha-tocopherol and for HPV detection. Higher serum level of alpha-carotene was significantly associated with decreased risk of cervical dysplasia after controlling for HPV infection and smoking status (odds ratio (OR) = 0.16, 95% confidence interval (CI) 0.04-0.62 for the highest as compared with the lowest tertile). Decreased risk for the highest tertile of serum lycopene (OR = 0.28) was marginally significant. Decreased risks observed for the highest tertiles of beta-carotene (OR = 0.65) and zeaxanthin/lutein (OR = 0.53), were not statistically significant.     

Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis

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.     

Serum lycopene, other carotenoids, and prostate cancer risk: a nested case-control study in the prostate, lung, colorectal, and ovarian cancer screening trial.

BACKGROUND: Reports from several studies have suggested that carotenoids, and in particular lycopene, could be prostate cancer-preventive agents. This has stimulated extensive laboratory and clinical research, as well as much commercial and public enthusiasm. However, the epidemiologic evidence remains inconclusive. MATERIALS AND METHODS: We investigated the association between prediagnostic serum carotenoids (lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein, and zeaxanthin) and risk of prostate cancer in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, a multicenter study designed to examine methods of early detection and risk factors for cancer. The study included 692 incident prostate cancer cases, diagnosed 1 to 8 years after study entry, including 270 aggressive cases, with regional or distant stage (n = 90) or Gleason score >or=7 (n = 235), and 844 randomly selected, matched controls. As study participants were selected from those who were assigned to annual standardized screening for prostate cancer, results are unlikely to be biased by differential screening, a circumstance that is difficult to attain under non-trial conditions. RESULTS: No association was observed between serum lycopene and total prostate cancer [odds ratios (OR), 1.14; 95% confidence intervals (95% CI), 0.82-1.58 for highest versus lowest quintile; P for trend, 0.28] or aggressive prostate cancer (OR, 0.99; 95% CI, 0.62-1.57 for highest versus lowest quintile; P for trend, 0.433). beta-Carotene was associated with an increased risk of aggressive prostate cancer (OR, 1.67; 95% CI, 1.03-2.72 for highest versus lowest quintile; P for trend, 0.13); in particular, regional or distant stage disease (OR, 3.16; 95% CI, 1.37-7.31 for highest versus lowest quintile; P for trend, 0.02); other carotenoids were not associated with risk. CONCLUSION: In this large prospective study, high serum beta-carotene concentrations were associated with increased risk for aggressive, clinically relevant prostate cancer. Lycopene and other carotenoids were unrelated to prostate cancer. Consistent with other recent publications, these results suggest that lycopene or tomato-based regimens will not be effective for prostate cancer prevention.     

Vitamins, carotenoids, dietary fiber, and the risk of gastric carcinoma: results from a prospective study after 6.3 years of follow-up

BACKGROUND: Numerous components of fruit and vegetables are considered to decrease the risk of gastric carcinoma. In the current prospective study, the authors examined the association between the intake of vitamins, carotenoids, and dietary fiber and vitamin supplement use and the incidence rate of gastric carcinoma. METHODS: The Netherlands Cohort Study began in 1986 with 120,852 men and women ages 55-69 years. Data regarding diet and other covariates were collected by means of a self-administered questionnaire. After 6.3 years of follow-up, data regarding 282 incident cases of gastric carcinoma and 3123 subcohort members were available for case-cohort analyses. RESULTS: In analyses adjusted for age, gender, smoking history, education, stomach disorders, and family history of gastric carcinoma, an inverse association with vitamin C intake (relative risk [RR] for highest vs. lowest intake category, 0.7; 95% confidence interval [95% CI], 0.5-1.0) was observed, with a borderline significant trend across three intake categories (P = 0. 06). After the exclusion of cases diagnosed in the first and second follow-up years, the RR was 0.9 (95% CI, 0.6-1.2; P trend = 0.44). Intake of retinol and beta-carotene were associated positively with gastric carcinoma risk with highest versus lowest quintile RRs of 1. 6 (95% CI, 1.0-2.5; P trend = 0.02) and 1.6 (95% CI, 1.0-2.6; P trend = 0.13), respectively, after the exclusion of first-year and second-year cases. Intake of folate, vitamin E, alpha-carotene, lutein plus zeaxanthin, beta-cryptoxanthin, lycopene, and dietary fiber was not associated with gastric carcinoma. Patients who used vitamin A-containing supplements had a lower risk of gastric carcinoma than nonusers (RR = 0.4; 95% CI, 0.2-0.9). CONCLUSIONS: No clear inverse associations were found between the intake of vitamins, carotenoids, and dietary fiber and the risk of gastric carcinoma after adjustment for confounding variables and the exclusion of first-year and second-year cases.     

Inverse associations between plasma lycopene and other carotenoids and prostate cancer.

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.     

Intake of the major carotenoids and the risk of epithelial ovarian cancer in a pooled analysis of 10 cohort studies

Carotenoids, found in fruits and vegetables, have the potential to protect against cancer because of their properties, including their functions as precursors to vitamin A and as antioxidants. We examined the associations between intakes of alpha-carotene, beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin and lycopene and the risk of invasive epithelial ovarian cancer. The primary data from 10 prospective cohort studies in North America and Europe were analyzed and then pooled. Carotenoid intakes were estimated from a validated food frequency questionnaire administered at baseline in each study. Study-specific relative risks (RR) were estimated using the Cox proportional hazards model and then combined using a random-effects model. Among 521,911 women, 2,012 cases of ovarian cancer occurred during a follow-up of 7-22 years across studies. The major carotenoids were not significantly associated with the risk of ovarian cancer. The pooled multivariate RRs (95% confidence intervals) were 1.00 (0.95-1.05) for a 600 microg/day increase in alpha-carotene intake, 0.96 (0.93-1.03) for a 2,500 microg/day increase in beta-carotene intake, 0.99 (0.97-1.02) for a 100 microg/day increase in beta-cryptoxanthin intake, 0.98 (0.94-1.03) for a 2,500 microg/day increase in lutein/zeaxanthin intake and 1.01 (0.97-1.05) for a 4,000 microg/day increase in lycopene intake. These associations did not appreciably differ by study (p-values, tests for between-studies heterogeneity >0.17). Also, the observed associations did not vary substantially by subgroups of the population or by histological type of ovarian cancer. These results suggest that consumption of the major carotenoids during adulthood does not play a major role in the incidence of ovarian cancer.     

Vegetable consumption and lung cancer risk: a population-based case-control study in Hawaii

We conducted a population-based study of diet and lung cancer among the multiethnic population of Hawaii in 1983-1985. We completed interviews for 230 men and 102 women with lung cancer and 597 men and 268 women controls, frequency-matched to the patients by age and sex. A quantitative dietary history assessed the usual intake of foods rich in vitamins A and C and carotenoids. A clear dose-dependent negative association was demonstrated between dietary beta-carotene and lung cancer risk in both sexes. After adjusting for smoking and other covariates, the men in the lowest quartile of beta-carotene intake had an odds ratio of 1.9 (95% confidence interval, 1.1-3.2) compared to those in the highest quartile of intake. The corresponding odds ratio for women was 2.7 (95% confidence interval, 1.2-6.1). No clear association was found for retinol, vitamin C, folic acid, iron, dietary fiber, or fruits. All vegetables, dark green vegetables, cruciferous vegetables, and tomatoes showed stronger inverse associations with risk than beta-carotene. This observation suggests that other constituents of vegetables, such as lutein, lycopene, and indoles, and others, may also protect against lung cancer in humans.     

Are retinol,vitamin C,vitamin E,folate and carotenoids intake associated with bladder cancer risk? Results from the Netherlands Cohort Study

In the Netherlands Cohort Study among 120 852 subjects aged 55-69 years at baseline (1986), the association between vitamins and carotenoids intake, vitamin supplement use, and bladder cancer incidence was examined. Exposure status was measured with a food-frequency questionnaire. After 6.3 years of follow-up, data from 569 cases and 3123 subcohort members were available for case-cohort analyses. The age-, sex-, and smoking-adjusted relative risks (RRs) for retinol, vitamin E, folate, a-carotene, b-carotene, lutein and zeaxanthin, and lycopene were 1.04, 0.98, 1.03, 0.99, 1.16, 1.11, and 1.08, respectively, comparing highest to lowest quintile of intake. Only vitamin C (RR: 0.81, 95% CI: 0.61-1.07, P-trend = 0.08), and b-cryptoxanthin intake (RR: 0.74, 95% CI: 0.53-1.03, P-trend < 0.01) were inversely associated with bladder cancer risk. The association with vitamin C disappeared after adjustment for b-cryptoxanthin but not vice versa. The RRs for supplemental use of vitamin A, C or E compared to no use were around unity. We conclude that dietary or supplemental intake of vitamin A, vitamin C, vitamin E, and intake of folate, and most carotenoids are not associated with bladder cancer. In this study, only b-cryptoxanthin intake appeared to be inversely associated.     

Vitamin and carotenoid intake and risk of squamous cell carcinoma of the skin

Our objective was to examine prospectively the intake of vitamins A (including retinol and total vitamin A), C and E; folate; total carotene; and several individual carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin and lutein/zeaxanthin) in relation to incidence of SCC of the skin in 2 large cohorts of men and women. We used a prospective cohort study design with up to 14 years of follow-up in women and 10 years in men. Diet was measured with FFQs every 2-4 years; cases of SCC of the skin were ascertained on biennial questionnaires and confirmed by medical records. Participants were female nurses and male health professionals, from the Nurses' Healthy Study and the Health Professionals Follow-up Study in the United States, without a history of any cancer in 1982 (n = 85,944 women) and 1986 (n = 43,867 men). Follow-up response was achieved for over 90% of potential person-years. Relative risks and 95% confidence intervals for development of SCC of the skin are reported. We recorded 369 cases of SCC in women and 305 cases in men. After multivariate adjustment for various known behavioral, sun-exposure and sun-sensitivity risk factors for SCC, there were no significant inverse associations between these dietary factors and SCC incidence. No evidence was found that vitamins A, C and E; folate; or carotenoids play an important protective role against incident SCC.     

Retinol, carotenoids and the risk of prostate cancer: a case-control study from Italy

Several studies have evaluated the possible association between intakes of retinoids and carotenoids and the risk of prostate cancer, but the evidence is still inconsistent. Further, only a few studies have investigated the role of specific carotenoids other than beta-carotene. We have thus considered the association between retinol and various carotenoids using data from a multicentric case-control study conducted in Italy between 1991 and 2002. This included 1,294 incident, histologically confirmed prostate cancer cases below age 75 years admitted to major teaching and general hospitals in the areas under study, and 1,451 controls below age 75 years selected among patients admitted to the same hospitals as cases for a wide spectrum of acute nonneoplastic conditions not related to long-term modifications of diet. Subjects' usual diet was investigated by means of a validated food-frequency questionnaire. Multivariate odds ratios and the corresponding 95% confidence intervals were estimated using unconditional logistic regression models. The risk of prostate cancer tended to decrease with increasing intake of retinol (OR=0.79 for the highest versus the lowest quintile of intake), carotene (OR=0.70), alpha-carotene (OR=0.85) and beta-carotene (OR=0.72), although the estimates were significant for carotene and beta-carotene only. No meaningful associations emerged for nonprovitamin A carotenoids, such as lycopene (OR=0.94) and lutein/zeaxanthin (OR=0.91). No systematic heterogeneity was observed across strata of age, education and body mass index. Thus, our study supports the hypothesis of a weak protective effect of carotene, particularly beta-carotene, on the risk of prostate cancer, while it indicates that other carotenoids, including lycopene, and retinol are not appreciably related to the risk of this neoplasm.