The long-term goal of the research proposed here is to generate new knowledge that can be applied to young women to prevent breast cancer. The theoretical Pike model of """"""""breast tissue age"""""""", and empirical epidemiological evidence, indicate that the breast is especially susceptible to the effects of carcinogens at early ages, and suggest that strategies of breast cancer prevention will be most effective if started early in life. Motivated by previous work that has shown variations in percent mammographic density (PMD) to be associated with large differences in risk of breast cancer in women of middle age and older, to be highly heritable, and strongly correlated with the water content of the breast as assessed by magnetic resonance (MR), we have examined factors associated with variations in breast tissue in young women using MR. To date we have examined 400 young women (aged 15-30 years), and their mothers. Breast MR has been used to characterize breast tissue in all young women and a random sample of 100 mothers. Mean levels and variation in breast water content were greatest in young women aged 15-18 years, when susceptibility to carcinogens is also greatest. We have found that the breast water content in young women is correlated with their weight and height, suggesting that general measures of growth and development are associated with breast tissue composition. Consistent with a previously described genetic influence, breast water content in young women was also associated with both the breast water content by MR and PMD of their mothers. We also found that blood levels of growth hormone and sex hormone binding globulin in all subjects were associated with breast water content. We thus have evidence that both hormonal and genetic factors influence breast tissue composition in young women. We propose here to recruit additional young women (aged 15-18 years) to add to those already examined, to provide a sample large enough to examine common genetic variation across the genome and the phenotypic features of breast tissue. This sample will also allow us to re-examine the associations of hormones and growth factors with breast tissue composition in this age group. The work completed to date has shown the feasibility of recruiting the number of young women required to achieve these aims. We will replicate results from the genome wide association study in young women in premenopausal women from whom DNA and collected and mammograms have been collected. To the best of our knowledge this is the first extensive study of breast tissue in young women, and the only study to date to show an association of endogenous sex hormones with breast tissue composition in this age group.
We propose to recruit young women, and their mothers, to add to those already examined, to provide a sample large enough for studies of genes associated with variations in breast tissue composition, and to provide data to confirm findings from previous work concerned with hormones and breast tissue composition. The proposed study will examine the relationship between genotype and the phenotypic features of breast tissue. The work completed to date has shown the feasibility of recruiting the number of young women required to achieve these aims. To the best of our knowledge this is the first extensive study of breast tissue in young women, when susceptibility to carcinogenic events is greatest, and variation in breast tissue composition is also greatest. Further, pregnancy, menopause, and other factors associated with ageing have not yet influenced breast tissue composition. For these reasons it may be easier at early ages to detect genetic effects, as well as the effects of environmental exposures unique to early life.
