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1. Introduction

Breast cancer is the most common cancer among women in the industrialized countries (WHO 1997). In Finland, breast cancer incidence has increased considerably during the last decades, accounting currently for one-third of the total cancer incidence in women (Finnish Cancer Registry 1997). In 1995, the number of new breast cancer cases was 3125, three times the number in the late 1960s. This trend toward an increase is expected to continue to the period 2008-2012, when 3860 new cases per year are predicted (Engeland et al. 1993). This trend is mainly explained by an increase in the number of elderly women in the population and strengthening of the effects of risk factors for breast cancer.

In spite of the increasing incidence, breast cancer mortality has remained largely unchanged because of improvements in diagnostic and treatment methods (see Harris et al. 1992). For example, the Finnish nationwide screening program since 1987 has decreased the breast cancer mortality of the participants by 24% (Hakama et al. 1997). In 1995, the number of deaths caused by breast cancer among Finnish women was 838 (Finnish Cancer Registry 1997).

A woman whose first-degree relative has had breast cancer is at increased risk herself (Hulka and Stark 1995). This risk is even higher if more than one first-degree relative has had breast cancer and if the cancer was diagnosed before the age of 60. In these situations, the estimated risk for breast cancer is two- to six-fold compared to women without a family history (see Harris et al. 1992). The discovery of the BRCA1 and BRCA2 tumor-suppressor genes in the 1990s has been an important milestone in breast cancer research (Miki et al. 1994, Wooster et al. 1994). Mutations in BRCA1 may account for 45% of the hereditary breast cancer, and almost all of hereditary cases in families with combined breast and ovarian cancer (Easton et al. 1993), while about 30% of high-risk breast cancer families are carriers of BRCA2 mutations. The initial estimates of the lifetime risk of breast cancer in BRCA1/BRCA2 carriers based upon studies in selected cancer-prone families were rather high, up to 84% by the age of 70 years (Ford et al. 1998). It has been estimated that inherited forms of breast cancer explain only 5% of all cases (Eeles et al. 1994). In Finland, however, low proportions of BRCA1 and BRCA2 mutations (altogether 21%) were found in breast cancer families (Vehmanen et al. 1997a, Vehmanen et al. 1997b). More evidence is needed for other susceptibility genes.

The constant increase in breast cancer incidence, geographical variation in breast cancer occurrence, and migrant studies offer evidence that risk factors other than genetic susceptibility exist. The known risk factors for female breast cancer, such as early menarche, late first full-term pregnancy, low number of births, and late menopause, are associated with endogenous hormones (Hulka and Stark 1995, World Cancer Research Fund 1997). There is also evidence that exogenous hormonal treatments, such as oral contraceptives or postmenopausal estrogen replacement therapy, may increase the risk, but the findings are inconclusive (Collaborative Group on Hormonal Factors in Breast Cancer 1996, Willis et al. 1996, Collaborative Group on Hormonal Factors in Breast Cancer 1997, Grodstein et al. 1997, Hankinson et al. 1997).

High hormone level, especially that of estrogens, plays a major role in the promotional phase of breast carcinogenesis by stimulating, together with other growth factors, the division and growth of breast tumor cells (Lipworth 1995). Insulin and insulin-like growth factor I (IGF-I) have also received attention as potential biological factors in the development of breast cancer (Del Giudice et al. 1998, Hankinson et al. 1998). Insulin and IGF-I decrease the level of blood sex hormone-binding globulin, and thus increase the level of bioavailable estrogens. It seems that these two substances may explain some of the observed associations between dietary factors and breast cancer. For example, high fat intake has been indicated as enhancing insulin resistance and increasing the level of insulin and insulin-like growth factors (see Stoll 1996). These associations may be explained by free fatty acids that affect insulin-signaling mechanisms and reduce insulin binding (Smith 1994).

The known risk factors have been estimated to explain less than half of the sporadic breast cancer (see Hankin 1993). Thus, some other factors, such as dietary factors and alcohol, may be related to its development. Doll and Peto (1981) reported that diet accounts for 10-70% of all cancer deaths in the United States, but revised the range to 20-60% in the early 1990s (Doll 1992). An expert panel has recently estimated that high vegetable consumption, regular physical activity, abstinence from alcohol, and maintenance of normal body weight may prevent more than 33% of breast cancer cases (World Cancer Research Fund 1997). However, only high alcohol consumption has consistently been associated with an increased risk of breast cancer, whereas the results for other dietary factors have been inconclusive. Genetic and hormonal factors are more often related to premenopausal breast cancer, whereas environmental factors are related to postmenopausal breast cancer (Henderson and Patek 1997).

This dissertation summarizes the results of associations between dietary factors, total lifetime alcohol consumption, toenail selenium concentration, body-size indicators, and risk of breast cancer in the Kuopio Breast Cancer Study. This case-control study was carried out in eastern Finland, where breast cancer incidence is somewhat lower than in southern or southwestern Finland. Dietary habits have been quite traditional in the east compared to the more modern habits of southern Finland, although the differences are diminishing rapidly. This study belongs to the field of nutritional epidemiology, which means that methods of nutrition science and cancer epidemiology were utilized in the analyses. All the patients were subjected to normal diagnostic procedures including clinical examination with inspection and palpation, radiological examinations (mammography or ultrasonography), and fine needle, core needle, or surgical biopsy, if necessary. In addition, the cytopathological or histopathological diagnoses were made according to the current practice at Kuopio University Hospital.

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