Hormonal, reproductive, and dietary factors play an important role in the aetiology of breast cancer (BC). Selenium (Se) is an essential micronutrient thought to aid cancer prevention via its incorporation into selenoproteins which help counter oxidative damage to DNA, proteins, and lipids. Such DNA damage also appears to play a notable role in BC initiation and development. Although we only need Se in small amounts, its availability in Irish and most European soils is often insufficient for optimum dietary levels. Low Se levels and variations in the genes encoding selenoproteins may influence a woman’s risk of developing BC, but this has not been adequately studied, especially before cancer onset. This project will measure in blood samples from a large prospective European cohort of women with BC (2,500 cases) matched to an equal disease-free number (2,500 controls) two markers of Se status (levels of Se and the main Se transport protein, Selenoprotein P). The activity of the anti-oxidant selenoprotein glutathione peroxidase will also be measured in 1,500 of these case-control pairs as evidence suggests it could be a potential marker of cancer risk in women taking HRT. We will additionally measure genetic differences in selenoprotein genes and related anti-oxidant enzyme genes in available DNA from 1,496 of these case-control pairs. Appropriate statistical data analysis methods will be used to determine if Se status levels and hereditary genetic variation in selenoprotein genes are significantly associated with BC risk in European populations, and if Se status and selenoprotein genetic changes together with other dietary/lifestyle factors interact to modify BC risk. The proposal will benefit from existing extensive epidemiologic and biomarker data for our study subjects. This project will help define the context of Se use for BC prevention in women whose Se status is sub-optimal and also for individuals of particular selenoprotein genotypes.
