BACKGROUND: Given the international variations in breast cancer incidence rates
and the changes in breast cancer incidence among migrant populations, it has
been hypothesized that diet is a factor influencing risk of this disease. Many
studies indicate that a diet high in vegetables and fruits may protect against
breast cancer. PURPOSE: We conducted a case-control study of diet, including the
intake of non-food supplements, and premenopausal breast cancer risk. We
evaluated in detail usual intake of vegetables and fruits (each measured as the
total reported grams consumed for all queried vegetables and fruit), vitamins C
and E, folic acid, individual carotenoids, and dietary fiber with its
components. METHODS: Case patients (n=297) were identified through pathology
records from hospitals in Erie and Niagara counties in western New York. They
consisted of premenopausal women 40 years of age or oder who were diagnosed with
breast cancer from November 1986 through April 1991. Control subjects (n=311),
frequency-matched to case patients on the basis of age and county of residence,
were randomly selected from New York State Department of Motor Vehicles records.
In-person interviews included detailed reports of usual diet in the period 2
years before the interview. Unconditional logistic regression was used to
estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: There
was a reduction in risk associated with high intake of several nutrients. With
the lowest quartile of intake as the referent, adjusted ORs for the highest
quartile of intake for specific nutrients were as follows: vitamin C (OR=0.53;
95% CI=0.33-0.86), alpha-tocopheral (OR=0.55; 95% CI=0.34-0.88), folic acid
(OR=0.50; 95% CI=0.31-0.82), alpha-carotene (OR=0.67; 95% CI=0.42-1.08) and
beta-carotene (OR=0.46; 95% CI=0.28-0.74), lutein + zeaxanthin (OR=0.47; 95%
CI=0.28.0-77), and dietary fiber from vegetables and fruits (OR=0.48; 95%
CI=0.30-0.78). No association with risk was found for beta-cryptoxanthin,
lycopene, or grain fiber. Fruits were weakly associated with a reduction in risk
(fourth quartile OR=0.67; 95% CI=0.42-1.09). No association was found between
breast cancer risk and intake of vitamins C and E and folic acid taken as
supplements. A strong inverse association between total vegetable intake and
risk was observed (fourth quartile OR=0.46; 95% CI=0.28-0.74). This inverse
association was found to be independent of vitamin C,alpha-tocopherol, folic
acid, dietary fiber, and alpha-carotene.Adjusting for beta-carotene or lutein +
zeaxanthin somewhat attenuated the inverse association with vegetable intake.
CONCLUSIONS: In this population, intake of vegetables appears to decrease
premenopausal breast cancer risk. This effect may be related, in part, to
beta-carotene and lutein + zeaxanthin in vegetables. It appears, however, that,
of the nutrients and food components examined, no single dietary factor explains the effect. Evaluated components found together in vegetables may have a synergistic effect on breast cancer risk; alternatively, other unmeasured
factors in these foods may also influence risk.

The incidence of adenocarcinomas of the esophagus and gastric cardia (ACEGC) has been increasing for the past 10-15 years in the United States. The reason for this increase is unknown. This hospital-based case-control study was conducted to assess the effects of dietary and nutritional factors on the risk of ACECG. A total of 95 incident cases with pathological diagnosis and 132 cancer-free controls were included in the study. Patients were recruited at Memorial Sloan-Kettering Cancer Center from 1 November 1992 to 1 November 1994. Epidemiologic data were collected by a modified National Cancer Institute Health Habits History Questionnaire. Nutritional and dietary factors were analyzed using a logistic regression model. Increased risk of ACEGC was significantly related to higher intake of dietary calories and fat after controlling for several potential confounding factors. Decreased risk of ACEGC was significantly associated with high ingestion of dietary fiber, lutein, niacin, vitamin B6, iron, and zinc. Higher intakes of vitamin A, beta-carotene, vitamin E, folate,
phosphorus, and potassium were associated with a decreased risk of the disease, but these were not statistically significant. The study suggests that ACEGC can be preventable through dietary interventions.

To examine whether dietary fiber modifies breast cancer risk, a case-control
study involving 351 newly diagnosed patients with breast cancer and 356
hospitalized controls was conducted in Uruguay. Dietary patterns were assessed in detail by use of a food frequency questionnaire on 64 items, which allowed the calculation of total energy intake. Nutrient residuals were calculated
through regression analysis. After adjustment for potential confounders (which
included age, residence, family history of breast cancer, prior history of
benign breast disease, parity, total energy, red meat, lutein/zeaxanthin and
quercetin intake, and menopausal status), dietary fiber and total nonstarch
polysaccharides were associated with a strong reduction in risk of breast cancer
(odds ratio for uppermost quartile of total dietary fiber = 0.51, 95% confidence
limit = 0.31-0.82). Also the dose-response pattern was highly significant (p <
0.001). The inverse association was observed in pre- and post-menopausal women and was similar for soluble and insoluble fiber. Furthermore, dietary fiber
displayed a strong joint effect with fat, quercetin, and lutein/zeaxanthin.

We determined whether intakes of the main dietary carotenoids (alpha-carotene,
beta-carotene, beta-cryptoxanthin, lutein plus zeaxanthin, and lycopene) and of
vitamins A, C, and E were associated with the prevalence of colorectal adenomas among male and female members of a prepaid health plan in Los Angeles who underwent sigmoidoscopy (n = 488 matched pairs). Participants, ages 50-74 years, completed a 126-item semiquantitative food-frequency questionnaire and a non-dietary questionnaire from 1991 to 1993. In the univariate-matched analysis, alpha-carotene, beta-carotene (with and without supplements), beta-cryptoxanthin, lutein plus zeaxanthin, vitamin A (with and without supplements), and vitamin C (with and without supplements) were associated with a decreased prevalence of colorectal adenomas. After adjustment for intake of calories, saturated fat, folate, fiber, and alcohol, and for current smoking status, body mass index, race, physical activity, and use of nonsteroidal anti-inflammatory drugs, only beta-carotene including supplements was inversely associated with adenomas (odds ratio (OR), 0.6; 95% confidence interval (CI), 0.41.1; trend, P= 0.04; ORs compare highest to lowest quartiles0; vitamin C showed a weaker inverse association (OR, 0.8; 95% CI, 0.5-1.5; trend, P = 0.08); and the remaining compounds were no longer clearly associated with risk. After including beta-carotene with supplements and vitamin C simultaneously in the mutivariate model, the association of beta-carotene with supplements with adenomas was weakened (OR, 0.8; 95% CI, 0.5-1.3; trend P = 0.15), and vitamin C was no longer associated with risk. These data provide only modest support for a protective association of beta-carotene with colorectal adenomatous polyps.

High intakes of antioxidants in fruit, vegetables and wine are thought to
protect against coronary heart disease (CHD). Because people in Toulouse have a much lower incidence of CHD compared with Belfast, the plasma concentrations of antioxidant vitamins and carotenoids in the two populations have been compared. The major difference was in some of the plasma carotenoids. Hydroxy-carotenoids were twice as high in Toulouse in both sexes, notably lutein which occurs principally in dark green vegetables and beta-cryptoxanthin which occurs chiefly in citrus fruits. In addition, alpha-carotene was 50% higher in Toulouse, gamma-tocopherol was 50% higher in Belfast. Other plasma vitamins and carotenoids were not significantly different. If antioxidants play a role in preventing CHD, then the hydroxy-carotenoids are major candidates for further investigation.

Among patients with breast cancer, tumors that contain estrogen receptors (ER)
are associated with improved survival and better response to hormone therapy
than those not expressing these receptors. The purpose of these case comparison studies was to examine the relationship between carotenoids, vitamin A, and the tumor ER status in women at diagnosis of primary breast cancer. The focus of the first study was the relationship between dietary intake and ER status, and the focus of the second study was the relationship between ER status and the plasma carotenoid, retinol, and tocopherol concentrations. We evaluated tumor ER status and self-reported dietary intake in 142 women and plasma concentrations of carotenoids, retinol, and tocopherols in 149 women, at diagnosis of breast cancer, before any medical or surgical treatment. In the first study the overall odds of ER-positive status were increased in relation to number of mammograms in the past five years, number of breast-fed babies, dietary carotenoid intake, and more frequent intake of yellow and green vegetables. Overall odds of ER-positive status were decreased in relation to years of oral contraceptive use and preformed vitamin A intake. In the second study older women, women with higher plasma lutein concentration, and women not using beta-carotene supplements were more likely to be ER positive, when data were adjusted for body mass index and factors that may influence breast cancer risk or hormonal status. Significant independent relationships between plasma retinol or tocopherol concentrations and ER status were not observed. The strong and independent relationships between carotenoid intake, plasma lutein concentration, and ER status may relate to observations linking a carotenoid-rich diet with improved prognosis after diagnosis of breast cancer.

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.

Epidemiologic data indicate that individuals with low plasma concentrations of
carotenoids and antioxidant vitamins and those who smoke cigarettes are at
increased risk for age-related macular degeneration (AMD). Laboratory data show that carotenoids and antioxidant vitamins help to protect the retina from
oxidative damage initiated in part by absorption of light. Primate retinas
accumulate two carotenoids, lutein and zeaxanthin, as the macular pigment, which is most dense at the center of the fovea and declines rapidly in more peripheral regions. The retina also distributes alpha-tocopherol (vitamin E) in a
nonuniform spatial pattern. The region of monkey retinas where carotenoids and
vitamin E are both low corresponds with a locus where early signs of AMD often
appear in humans. The combination of evidence suggests that carotenoids and
antioxidant vitamins may help to retard some of the destructive processes in the
retina and the retinal pigment epithelium that lead to age-related degeneration
of the macula.

Incidence rates of lung cancer have been markedly lower for Fiji than for other
South Pacific countries, despite similar rates of smoking. We conducted
population-based surveys in several island nations of the South Pacific (Cook
Islands, Fiji, Tahiti and New Caledonia) and used data from Caucasian, Japanese, Hawaiian, Filipino and Chinese controls in a case-control study of lung cancer in Hawaii to investigate the role of diet in explaining differences in lung cancer incidence among 20 ethnic-sex groups. In a stepwise linear regression of lung cancer rates on smoking, diet and other variables, smoking, as expected, explained the majority (61%) of the variability in incidence. However, several dietary components also explained significant portions of the variance. Lutein intake explained 14% and vitamin E intake, cholesterol intake and height explained 5-7% each of the remaining variance in incidence. Associations with lutein and vitamin E were inverse, whereas those with cholesterol and height were direct. Dietary beta-carotene intake was not associated with lung cancer incidence. These ecological data provide evidence for a protective effect of lutein against lung cancer. A protective effect of dietary vitamin E and a risk-enhancing effect of dietary cholesterol are also suggested.

Epidemiological investigations have shown that cancer risk is inversely related
to the consumption of green and yellow vegetables and fruits. Since
beta-carotene is present in abundance in these vegetables and fruits, it has
been investigated extensively as a possible cancer preventive agent. However,
various carotenoids that coexist with beta-carotene in vegetables and fruits
also have anticarcinogenic activity. Some of them, such as alpha-carotene,
showed higher potency than beta-carotene in suppressing experimental
carcinogenesis. Thus, we have carried out more extensive studies on
cancer-preventive activities of natural carotenoids, which found that lycopene
and lutein had potent anticarcinogenic activity. In the present study, the
cancer-preventive activity of phytoene was also confirmed biotechnologically
when mammalian cells producing phytoene were resistant to H-ras-induced cell
transformation. Further studies on various natural carotenoids besides
beta-carotene should be continued to obtain more information about the potential of natural carotenoids in the field of cancer prevention.