Dietary carotenoids and risk of breast cancer

BACKGROUND: Many studies of fruit and vegetable consumption showed inverse associations with breast cancer risk, suggesting the potential importance of carotenoids (and other phytochemicals) contained in these foods. To date, however, only one prospective cohort study has examined dietary carotenoids other than beta-carotene in relation to breast cancer risk. OBJECTIVE: Our aim was to examine the relations between dietary intakes of beta-carotene, alpha-carotene, beta-cryptoxanthin, lycopene, and lutein + zeaxanthin and breast cancer risk in a large cohort study of Canadian women. DESIGN: A case-cohort analysis was undertaken in a cohort of 56 837 women who were enrolled in the Canadian National Breast Screening Study and who completed a self-administered dietary questionnaire. During follow-up to the end of 1993 a total of 1589 women were diagnosed with biopsy-confirmed incident breast cancer. For comparison, a subcohort of 5681 women was randomly selected. After exclusions for various reasons, the analyses were based on 1452 cases and 5239 noncases. RESULTS: We found no clear association between intakes of any of the studied carotenoids and breast cancer risk in the study population as a whole or in subgroups defined by smoking status; relative body weight (assessed by body mass index); intakes of total fat, energy, alcohol, or folic acid; family history of breast cancer; or menopausal status. CONCLUSIONS: Our data do not support any association between dietary intakes of the studied carotenoids and breast cancer risk. However, prospective cohort studies of carotenoids in relation to breast cancer are scarce and further studies are warranted.     

Dietary carotenoids and risk of breast cancer in Chinese women

There has been considerable interest in the role of carotenoids in the chemoprevention of cancer. However, the protective effect of carotenoids on breast cancer has been inconclusive. To investigate whether intake of lycopene, alpha-carotene, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin is inversely associated with breast cancer risk, a case-control study was conducted in China during 2004-2005. The cases were 122 female patients aged 24-87 years with histopathologically confirmed breast cancer. 632 healthy women age-matched were randomly recruited from outpatient clinics. Habitual dietary intake and lifestyle were collected by face-to-face interview using a validated and reliable food frequency questionnaire. The USDA nutrient composition database was used to calculate intake of the specific carotenoids. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), accounting for age, locality, education, body mass index, smoking, passive smoking, physical activity, number of children breastfed, menopausal status, oral contraceptive use, biopsy-confirmed benign breast diseases, family history of breast cancer, and total energy intake. Compared with the highest versus lowest quartile of intake, the adjusted ORs were 0.26 (95% CI 0.14-0.46) for lycopene, 0.38 (95% CI 0.21-0.71) for beta-carotene, 0.43 (95% CI 0.23-0.82) for beta-cryptoxanthin, and 0.37 (95% CI 0.20-0.68) for total carotenoids, with statistically significant tests for trend. There was no association with breast cancer for alpha-carotene and lutein/zeaxanthin. It is concluded that higher intake of lycopene, beta-carotene and beta-cryptoxanthin is associated to a lower risk of breast cancer among Chinese women. More research to examine the relationship between carotenoids and breast cancer risk is warranted.     

Plasma carotenoids, retinol, and tocopherols and risk of breast cancer

The roles of carotenoids, retinol, and tocopherols in breast cancer etiology have been inconclusive. The authors prospectively assessed the relations between plasma alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, lutein/zeaxanthin, retinol, alpha-tocopherol, and gamma-tocopherol and breast cancer risk by conducting a nested case-control study using plasma collected from women enrolled in the Nurses' Health Study. A total of 969 cases of breast cancer diagnosed after blood draw and prior to June 1, 1998, were individually matched to controls. The multivariate risk of breast cancer was 25-35% less for women with the highest quintile compared with that for women with the lowest quintile of alpha-carotene (odds ratio (OR) = 0.64, 95% confidence interval (CI): 0.47, 0.88; p(trend) = 0.01), beta-carotene (OR = 0.73, 95% CI: 0.53, 1.02; p(trend) = 0.01), lutein/zeaxanthin (OR = 0.74, 95% CI: 0.55, 1.01; p(trend) = 0.04), and total carotenoids (OR = 0.76, 95% CI: 0.55, 1.05; p(trend) = 0.05). The inverse association observed with alpha-carotene and breast cancer was greater for invasive cancers with nodal metastasis. The authors conclude that some carotenoids are inversely associated with breast cancer. Although the association was strongest for alpha-carotene, the high degree of collinearity among plasma carotenoids limits our ability to conclude that this association is specific to any individual carotenoid.     

Serum fatty acids and breast cancer incidence

Fatty acid composition of the diet may be essential to the development of breast cancer. We studied the ability of several fatty acids of serum total lipids to predict breast cancer incidence in a case-control study nested within a longitudinal population study. The proportions of fatty acids in serum total lipids were determined from stored serum samples collected at baseline for 127 incident breast cancer cases and 242 matched controls. Women with a higher proportion of total polyunsaturated fatty acids (PUFAs) in serum had a reduced risk of breast cancer. The odds ratio (OR) between the highest and lowest tertiles of serum PUFA was 0.31 (95% confidence interval, CI = 0.12-0.77). This association was mainly due to n-6 PUFAs and especially to linoleic acid. The ORs were 0.35 (CI = 0.14-0.84) and 0.29 (CI = 0.12-0.73), respectively. Of the monounsaturated fatty acids (MUFAs), higher trans-11-18:1 levels were related to an increased breast cancer risk (OR = 3.69, CI = 1.35-10.06). The association was stronger in postmenopausal than in premenopausal women. The present study suggests that higher serum proportions of the n-6 PUFA linoleic acid and lower proportions of the MUFA trans-11-18:1 fatty acid predict a reduced incidence of breast cancer.     

Skin carotenoids are inversely associated with adiposity in breast cancer survivors

Carotenoids are antioxidants which may mitigate some of the adverse effects of obesity, a condition associated with poor outcomes in breast cancer patients. We hypothesized that baseline skin carotenoids would be inversely associated with adiposity in breast cancer survivors and would increase with weight loss. Skin carotenoid score (SCS) was assessed by resonance Raman spectroscopy in breast cancer survivors (body mass index ≥25 kg/m²) enrolled in a 6-month randomized controlled weight loss trial (n = 47). Measurements included total body fat using dual-energy X-ray absorptiometry, height, weight, waist and hip circumference, dietary intake, and serum biomarkers. Associations between SCS, adiposity measures, and serum biomarkers were assessed at baseline, as was the change in SCS from baseline to 6 months, in the intervention and usual care groups. At baseline, SCS was inversely correlated with all adiposity measures (P ≤ .05). In multivariate analyses, baseline percent body fat had the strongest association with baseline SCS (partial R²= 0.20). Baseline SCS was significantly inversely associated with log C-reactive protein levels (regression coefficient β ± SE: −0.051± 0.019; P = .011) and log leptin (β ± SE: −0.019± 0.009; P = .046), but the associations were no longer significant after adjustment for adiposity. Over the 6-month study, the intervention group had a 17.6% increase in SCS compared to a 1.5% decrease in the usual care group (P = .28). In our study of overweight and obese breast cancer survivors, dual-energy X-ray absorptiometry–measured body fat explained a large portion of the variation in skin carotenoids at baseline, suggesting a stronger association than that previously seen in studies using less accurate measures of adiposity.     

Prostate cancer and dietary carotenoids

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.     

Serum carotenoids and markers of inflammation in nonsmokers

One explanation for discrepant results between epidemiologic studies and randomized trials of beta-carotene and cardiovascular disease may be a failure to consider inflammation as a confounder. To evaluate the potential for such confounding, the authors relate the serum concentrations of five carotenoids (alpha-carotene, beta-carotene, beta-cryptoxanthin, lycopene, and lutein/zeaxanthin) to levels of three inflammatory markers (C-reactive protein, fibrinogen, and white blood cell count) measured during the Third National Health and Nutrition Survey, 1988-1994. The analysis included 4,557 nonsmoking participants aged 25-55 years. Adjusted concentrations of all five carotenoids were significantly lower in those with C-reactive protein levels above 0.88 mg/dl (p = 0.001). There was a trend toward lower adjusted beta-cryptoxanthin concentrations with increasing level of fibrinogen (p value test for trend = 0.01), but other carotenoids were not related. Many of the carotenoid concentrations were lower among participants with high white blood cell counts. After log transformation, only adjusted mean beta-carotene levels were significantly lower in those with white blood cell counts above 7.85 x 10(9)/liter (p < 0.01). These cross-sectional data do not clarify the biologic relation between carotenoids and C-reactive protein but, to the extent that the carotenoids are associated with C-reactive protein levels, a carotenoid-heart disease association may be, in part, an inflammation-heart disease association.     

Serum carotenoids, retinol, and tocopherols, and colorectal cancer risk in a Japanese cohort: effect modification by sex for carotenoids

To examine associations of serum carotenoids, retinol, and tocopherols with colorectal cancer risk, we conducted a case-control study nested within the Japan Collaborative Cohort Study. These micronutrients were measured in prediagnostic serum samples from 116 men and women who developed colorectal cancer during an 8-yr follow-up period and from 298 matched controls. In men, the higher level of serum total carotenoids was associated with a decreased risk: The multivariate-adjusted odds ratio (OR) for the highest vs. the lowest tertile was 0.34 (95% confidence interval [CI] = 0.11-1.00; trend P over tertiles = 0.040). In women, the higher levels of alpha- and and total carotenoids were instead related to an increased risk: The corresponding ORs were 4.72 (95% CI = 1.29-17.3), 2.00 (0.70-5.73), and 2.47 (0.73-8.34), respectively (trend P = 0.007, 0.040, and 0.064, respectively). We also found a somewhat decreasing risk with increased serum retinol in all subjects and alpha-tocopherol in men: The ORs (95% CI) for the highest tertiles were 0.29 (0.11-0.78; trend P over tertiles = 0.010) and 0.29 (0.07-1.17; trend P = 0.098), respectively. The effects of some carotenoids on colorectal cancer risk may be modified by sex or by factors associated with sex, including smoking and drinking habits.     

Serum carotenoids and pulmonary function in older community-dwelling women

Background and Objectives

Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake.

Subjects and Methods

We examined the relationship between serum ??-carotene, ??-carotene, ??-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV₁] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women??s Health and Aging Study I) in Baltimore, Maryland, USA.

Results

Higher serum ??-carotene and ??-carotene concentrations were positively associated with both FEV₁ and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between ??-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV₁ or FVC.

Conclusions

Higher serum ??-carotene and ??-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints.     

Serum lycopene,other serum carotenoids,and risk of prostate cancer in US Blacks and Whites

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.     

Intake of specific carotenoids and essential fatty acids and breast cancer risk in Montreal, Canada

BACKGROUND: Evidence from previous investigations into the possible role of dietary and serum carotenoid concentrations in the etiology of breast cancer is inconsistent. No study has examined the combined effect of carotenoids and essential fatty acids on the risk of breast cancer. OBJECTIVE: The objective was to assess the possible association between specific and total carotenoids and breast cancer risk and to evaluate the effect modification by diet-related fatty acids and lifestyle factors in the development of breast cancer. DESIGN: A population-based case-control study involving 414 incident cases and 429 controls was conducted in French Canadians in Montreal. Dietary intake was estimated with the use of a validated food-frequency questionnaire in face-to-face interviews. RESULTS: No significant association was apparent between any of the individual or total carotenoids and the risk of breast cancer after adjustment for major underlying determinants of breast cancer. In premenopausal women who ever smoked, an increased risk was related to alpha-carotene [odds ratio (OR) for the upper relative to the lowest quartiles of intake: 2.40; 95% CI: 0.90, 6.41; P for trend = 0.046]. Conversely, a reduced risk was related to beta-carotene (OR: 0.57; 95% CI: 0.26, 1.24; P for trend = 0.05) in women who never used hormone replacement therapy. In postmenopausal women, total carotenoids were positively associated with breast cancer risk in those with a high arachidonic acid intake (OR: 1.92; 95% CI: 0.93, 3.94; P = 0.028 for trend) and inversely associated in those with a high docosahexaenoic acid intake (OR: 0.52; 95% CI: 0.25, 1.07; P for trend = 0.054). CONCLUSION: These findings suggest that the combined high intake of total carotenoids and docosahexaenoic acid may reduce the risk of breast cancer.     

Plasma carotenoids are biomarkers of long-term high vegetable intake in women with breast cancer

We investigated predictors of change in plasma carotenoids from baseline to 3 y and examined plasma carotenoid concentrations at 1 and 3 y in response to a high vegetable diet. Participants were 56 women diagnosed with breast cancer and enrolled in a randomized feasibility study for a trial examining the effect of a diet high in vegetables and fruits on the risk of breast cancer recurrence. Independent t test analysis revealed that the intervention group had significantly higher vegetable and fruit servings and fiber at 12 mo and significantly higher vegetable servings at 36 mo compared with the control group (P < 0.05). Energy intake from fat was significantly lower in the intervention group at 12 and 36 mo. The intervention group had significantly higher consumption of beta-carotene, alpha-carotene, lutein and beta-cryptoxanthin at 12 mo (P < 0.05). beta-Carotene, alpha-carotene and lutein intakes also were significantly higher at 36 mo (P < 0.05). At 36 mo, the intervention group had significantly higher plasma concentrations of alpha-carotene and beta-carotene compared with the control group. Repeated-measures ANOVA revealed that the intervention group had significantly increased (P < 0.05 with Bonferroni correction) plasma beta-carotene, alpha-carotene, lutein and lycopene concentrations at 12 and 36 mo compared with baseline. Baseline carotenoid concentrations were significantly inversely predictive (P < 0.05) of plasma carotenoid change. In addition, change in body mass index (BMI) and plasma cholesterol concentrations were predictive of plasma carotenoid change from baseline to 3 y. Results of this study demonstrate that change in plasma carotenoid concentrations is associated with change in BMI, change in plasma cholesterol and baseline carotenoid concentrations. Plasma carotenoid response can be an indicator of long-term high vegetable intake for women at risk of breast cancer recurrence.     

Retinoids, carotenoids, and human breast cancer cell cultures: a review of differential effects

Cancer of the breast is the most common incident cancer and cause of death from cancer in women. Several epidemiologic studies have reported a significant inverse relationship between the intake of vitamin A and/or provitamin A-rich foods and the incidence of certain cancers, including breast cancer. A large number of studies have been conducted to determine the effect of retinoids (all-trans-retinoic acid, in particular), and to a lesser extent of carotenoids, on breast cancer using cell culture models. In general, the results of these studies demonstrate beneficial effects of all-trans-retinoic acid on different breast cancer cells. This review compares studies conducted in different laboratories using retinoids and carotenoids as treatments for breast cancer cells and suggests what may be the underlying reasons for the differential effects of these compounds on the same cell lines.     

Serum vitamins A and E,beta-carotene,and selenium in patients with breast cancer.

A total of 89 subjects including 30 breast cancer patients with distal metastases, 29 patients with benign breast disease, and 30 healthy subjects were studied. Serum samples from these subjects were obtained from the National Cancer Institute (NCI) Breast Cancer Serum Bank, Bethesda. Serum concentrations of vitamin A and its transport proteins (prealbumin and retinol-binding protein [RBP]), beta-carotene, vitamin E, and selenium were determined. For each of these parameters the mean for the breast cancer patients was lower than that of the healthy subjects. The differences between healthy subjects and patients with either breast cancer or benign breast disease were, however, statistically significant only in the case of RBP (p less than 0.05). In the case of vitamin A and its transport proteins these differences were reduced by comparing the cancer patients with the benign breast disease patients rather than with the healthy controls. This indicates that the low serum levels for those three parameters may be merely a consequence of disease in general rather than a feature of cancer per se.     

Relationship between plasma carotenoids and prostate cancer

Carotenoids, particularly lycopene, are thought to decrease prostate cancer risk, but the relationship between plasma carotenoid concentrations and risk in various populations has not been well characterized. Comparing 118 non-Hispanic Caucasian men mainly from southeast Texas with nonmetastatic prostate cancer with 52 healthy men from the same area, we conducted a case-control analysis evaluating associations between risk and plasma levels of total carotenoids, beta-cryptoxanthin, alpha- and trans-beta-carotene, lutein and zeaxanthin, total lycopenes, trans-lycopene, total cis-lycopenes, and cis-lycopene isoforms 1, 2, 3, and 5. Risk for men with high plasma levels of alpha-carotene, trans-beta-carotene, beta-cryptoxanthin, and lutein and zeaxanthin was less than half that for those with lower levels. In contrast, we observed no significant associations for total lycopenes, all-trans-lycopene, and cis-lycopene isomer peaks 2, 3, and 5, although high levels of cis-lycopene isomer peak 1 were inversely associated with risk. Analysis of men with aggressive disease (Gleason scores of > or =7, n = 88) vs. less aggressive cases (Gleason scores of <7, n = 30) failed to reveal significant associations between carotenoid levels and the risk of diagnosis with aggressive disease. These findings suggest that, in these men, higher circulating levels of alpha-cryptoxanthin, alpha-carotene, trans-beta-carotene, and lutein and zeaxanthin may contribute to lower prostate cancer risk but not to disease progression.     

Costs of breast cancer and the cost-effectiveness of breast cancer screening.

Breast cancer is the second leading cause of death by cancer among women in the United States. The total cost of illness for breast cancer has been estimated to be $3.8 billion, of which $1.8 billion represents medical care costs. It has been estimated that breast cancer detected early is considerably less expensive than when the tumor is discovered at a later stage. Mass screening using mammography can improve early detection by as much as 15-35%. Cost-effectiveness studies have estimated that the costs of breast cancer screening range between $13,200 and $28,000 per year of life saved. The cost-effectiveness of breast cancer screening in the 40-49-year-old age group is controversial. Mass screening for breast cancer will probably increase total health care costs, but when all economic costs are included, screening appears to be more cost-effective than not screening.