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ANTIOXIDANTS, MYOCARDIAL INFARCTION AND BREAST CANCER

Objective

The EURAMIC multi-center case-control study was undertaken to test the hypothesis that male myocardial infarction (MI) cases and female breast cancer (BC) cases have a lower antioxidant status than control subjects without these disease. Antioxidant status is assessed as the concentration of vitamin E and beta-carotene in adipose tissue, and of selenium in toenails.
The European study on antioxidants myocardial infarction and cancer of the breast (EURAMIC) multicentre case control study was undertaken to test the hypothesis that male myocardial infarction (MI) cases and female breast cancer (BC) cases have a lower antioxidant status than control subjects without these diseases. Antioxidant status is assessed as the concentration of vitamin E and beta carotene in adipose tissue, and of selenium in toenails. Data collection ended 31 October 1992 for the MI study, and 31 December 1992 for the BC study. For the MI study biomarker data has been collected for 712 cases and 733 controls. For the BC study the number of cases and controls is 318 and 466 respectively. The distribution of coronary heart disease (CHD) risk factors in the different centres has been analysed for 90% of the data. Classical risk factors like smoking, hypertension and diabetes are significantly more prevalent in the cases. Laboratory analysis of antioxidants has not yet been completed. Mean alpha tocopherol and beta carotene levels, as well as a risk estimate for low pressure levels have been produced for 40% of the data. Remarkable differences exist between centres, southern countries showing a relatively low beta carotene level, but also the variation within centres is large. Small numbers for some centres in the analysis do not permit any conclusions to be drawn so far. Estimates of the relative risk of MI at low antioxidant levels show an increased risk for low adipose tissue beta carotene, but none for alpha tocopherol. These findings need further exploration, including possible interactions. Results for selenium status for about 1200 subjects have been obtained recently and data analysis is in progress.
Many studies have implicated free radical oxidative reactions in age-related disorders, such as cardiovascular and malignant disease. Antioxidants are compounds that inhibit oxidative reactions by scavenging reactive oxygen-derived radicals and/or by interfering with the chain-reaction of peroxidation. Both vitamins (e.g. alpha-tocopherol, beta-carotene, ascorbic acid) and enzyme-linked trace-elements (e.g. selenium, copper, zinc) are essential components of the antioxidant defense of the body.
It is hypothesized that the risk of developing age-related diseases is influenced by the balance between oxidant stress and antioxidant defense.
The fat-soluble antioxidants alpha-tocopherol and beta-carotene and the trace element selenium were investigated in the EURAMIC Study. These three substances may all be derived from usual dietary sources. Although the protective role of these substances has been studied separately in epidemiologic studies, their joint action over a wide range of dietary intake and antioxidant status is not well elaborated. As antioxidant requirements are related to fatty acid intake, especially of polyunsaturates, fatty acid composition is of additional interest.

Acute myocardial infarction and breast cancer have been selected as the diseases of interest. The sudden clinical occurrence of a first myocardial infarction and the diagnosis of breast cancer in an early stage, avoid secondary changes in life-style and exposure status.
Acute myocardial infarction is a major contributor to cardiovascular disease morbidity and mortality in men and postmenopausal women. In addition to increased disease risk from smoking, elevated serum cholesterol and blood-pressure, antioxidants may beneficially affect cardiovascular disease risk by reducing oxygen-induced damage to lipids, lipoproteins and endothelial tissue. Breast cancer is the most important cancer among European women. In addition to reproductive and hormonal factors, which do not lend themselves to preventive measures, dietary factors including the natural antioxidants may be involved. Antioxidants may prevent oxygen-related DNA-damage in ductal epithelium of the mammary gland.

For acute myocardial infarction and breast cancer, the following hypotheses were tested in the EURAMIC Study:
1 The concentration of alpha-tocopherol and beat-carotene in adipose tissue, and of selenium in toenails is lowered in cases as compared to healthy population controls.
2 The shape of the antioxidant-disease relationship is non-linear, i.e. the increased risk may be most pronounced at low antioxidant concentration.
3 The antioxidants affect disease-risk synergistically, in particular for alpha-tocopherol and selenium. Furthermore, the alleged protective effect of beta-carotene may be particularly important at low alpha-tocopherol/selenium status or in smokers experiencing high oxidant stress.

Funding Scheme

CON - Coordination of research actions

Coordinator

TNO Food and Nutrition Institute
Address

3700 AJ Zeist
Netherlands