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Life Extension Magazine

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May 2002

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Breast cancer/vitamin E

Does lack of tocopherols and tocotrienols put women at increased risk of breast cancer?

Breast cancer is the leading site of new cancers in women and the second leading cause (after lung cancer) of cancer mortality in women. Observational studies that have collected data for dietary exposure to alpha-tocopherol with or without the other related tocopherols and tocotrienols have suggested that vitamin E from dietary sources may provide women with modest protection from breast cancer. However, there is no evidence that vitamin E supplements confer any protection whatever against breast cancer. Observational studies that have assessed exposure to vitamin E by plasma or adipose tissue concentrations of alpha-tocopherol have failed to provide consistent support for the idea that alpha-tocopherol provides any protection against breast cancer. In addition, evidence from studies in experimental animals suggest that alpha-tocopherol supplementation alone has little effect on mammary tumors. In contrast, studies in breast cancer cells indicate that alpha- gamma-, and delta-tocotrienol, and to a lesser extent delta-tocopherol, have potent antiproliferative and proapoptotic effects that would be expected to reduce risk of breast cancer. Many vegetable sources of alpha-tocopherol also contain other tocopherols or tocotrienols. Thus, it seems plausible that the modest protection from breast cancer associated with dietary vitamin E may be due to the effects of the other tocopherols and the tocotrienols in the diet. Additional studies will be required to determine whether this may be the case, and to identify the most active tocopherol/tocotrienol.

J Nutr Biochem 2002 Jan;13(1):2-20

Diet and the risk of breast cancer in a case-control study: does the threat of disease have an influence on recall bias?

It has been suggested that recall bias may explain the discrepant results between case-control and cohort studies on diet and the risk of breast cancer. Two control groups were used for this case-control study of 25 to 75-year-old breast cancer cases (n = 310). The first group consisted of population controls drawn from the Finnish National Population Register (n = 454). The second group consisted of women who were referred to the same examinations as were the cases because of clinical suspicion of breast disease but who were later diagnosed as healthy (referral controls; n = 506). Because the diagnosis was unknown at the time of interview, it was possible to assess by comparing the two control groups whether the self-reporting of diet changed under the threat of disease. Dietary habits were examined using a validated, self-administered food-frequency questionnaire. Premenopausal women misreported their consumption of liquid milk products, tea and sugar. Reporting bias was also associated with the intake of fat and vitamins. Postmenopausal women misreported consumption of milk products. When recall bias was taken into consideration, milk was associated with increased risk of premenopausal breast cancer, whereas high consumption of poultry or high intake of monounsaturated fatty acids, n-3 fatty acids, n-6 fatty acids and vitamin E were related to lower risk. The study suggested that oil, milk, cheese, coffee and beta-carotene may act as protective factors in postmenopausal women, whereas butter and cream may be risk factors for breast cancer. In summary, it is possible that some food items may be overreported or underreported under the threat of disease in health-conscious population. However, most of the results in this study were not modified by recall bias.

J Clin Epidemiol 1999 May;52(5):429-39

Interaction of family history of breast cancer and dietary antioxidants with breast cancer risk (New York, United States).

We sought to determine if specific dietary antioxidants may be particularly effective in reducing breast cancer risk for women reporting family history (FH) of breast cancer in a first-degree relative. Interviews regarding usual diet, health and family histories were conducted with 262 premenopausal and 371 postmenopausal women with incident, primary breast cancer from western New York (United States). These women were frequency-matched by age and county of residence with community controls. Among premenopausal women, there was a significant interaction between FH and alpha-tocopherol; alpha-tocopherol was associated with significantly decreased risk among FH+ women (adjusted fourth-quartile odds ratio [OR] = 0.01, 95 percent confidence interval [CI] = 0.0-0.3). This association was much weaker for FH- women [OR = 0.7, CI = 0.4-1.2]. For FH- women, a significant inverse association was observed between beta-carotene and premenopausal breast-cancer risk (OR = 0.4, CI = 0.3-0.5), but not for FH+ women (OR = 0.5, CI = 0.1-4.0). Similar relationships, although not as strong, were noted among postmenopausal women. Although limited by small numbers, these results suggest that biologic mechanisms of tumorigenesis may differ in FH+ and FH- women, and that alpha-tocopherol may be a potential chemopreventive agent for women with a family history of breast cancer, particularly premenopausal women.

Cancer Causes Control 1995 Sep;6(5):407-15

Premenopausal breast cancer risk and intake of vegetables, fruits and related nutrients.

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.

J Natl Cancer Inst 1996 Mar 20;88(6):340-8

The role of fat, animal protein and some vitamin consumption in breast cancer: a case control study in southern France.

The role of the consumption of fat, animal protein and vitamins on breast-cancer risk was investigated in a hospital-based case-control study of 924 patients (409 cases and 515 controls) in Montpellier (France). A dietary history questionnaire, administered by interview, comprising 55 key food items as well as beverage consumption, and including food frequencies and portion sizes, was used to measure the intake of total fat and its constituents, animal protein, retinol, beta-carotene, vitamin E and alcohol consumption. The questionnaire also elicited information on relevant medical history and personal characteristics. All food items which showed significantly elevated odds ratio (high-fat cheese, desserts and chocolate and processed pork meat) in a multivariate analysis contained a high proportion of animal fat. This is reflected in the nutrient analysis, which showed a significant linear trend as well as an elevated odds ratio for the highest tertile of consumption of total fat [OR3 = 1.6 (1.1-2.2)], animal fat [OR3 = 1.6 (1.1-2.2)], saturated fat [OR3 = 1.9 (1.3-2.6)] and mono-unsaturated fat [OR3 = 1.7 (1.2-2.5)]. For post-menopausal women, there is a particularly strong association with saturated fat [OR3 = 3.3 (1.4-7.8)] in a multivariate analysis including all other significant nutrients. There is no evidence of an increase of risk with the intake of animal protein and no evidence of risk reduction with increased consumption of vegetables, beta-carotene or vitamin E. Along with some recent studies, our results give support to the hypothesis that dietary fat is a risk factor in breast carcinogenesis.

Int J Cancer 1991 Apr 22;48(1):1-9\

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