) A P01 on the genetic epidemiology of breast cancer is proposed. It builds upon a unique resource of 426 four-to five-generation families ascertained through breast cancer patients originally ascertained between 1940 and 1952. Important observations have enriched this resource during 5 years of funding from an R01. The theme of this project is the interaction of genes and environment in the pathogenesis of this disease. These multi generation families offer distinct advantages in efforts to investigate this important subject. Project 1 seeks to I) determine the frequency of genetic alterations in BRCA1 and BRCA2 in a population-based sample of 260 families with at least two cases of breast or ovarian cancer and, II) to explore geno-environment risk interactions. Project 2 is designed to test the hypothesis that Bioactivation of estrogens, under the control of polymorphic genes, can lead to direct genotoxicity of DNA and increased risk of breast cancer. Project 3 is a genetic linkage study to identify the chromosomal location of a gene that is associated with increased mammographic breast density, a major risk factor for breast cancer. Project 4 is a follow up study of this powerful cohort of families. It seeks to investigate the natural history of mammographic breast density, and will examine important new risk factor data on adolescent diet and early life exposures. In addition, this follow-up survey will ascertain additional breast cancer cases for Projects 1 and 2. The projects are supported by four cores that are essential to carry out the overall P01: administration, biostatistics, mammography, and epidemiology. The investigative team is multidisciplinary, experienced, and brings a history of productive collaborations. The findings from this important project could be critical to our understanding of the genetic epidemiology of breast cancer.
| Darabi, Hatef; McCue, Karen; Beesley, Jonathan et al. (2015) Polymorphisms in a Putative Enhancer at the 10q21.2 Breast Cancer Risk Locus Regulate NRBF2 Expression. Am J Hum Genet 97:22-34 |
| Kelemen, Linda E; Atkinson, Elizabeth J; de Andrade, Mariza et al. (2010) Linkage analysis of obesity phenotypes in pre- and post-menopausal women from a United States mid-western population. BMC Med Genet 11:156 |
| Manduca, Armando; Carston, Michael J; Heine, John J et al. (2009) Texture features from mammographic images and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 18:837-45 |
| Sinicrope, Pamela S; Patten, Christi A; Clark, Lara P et al. (2009) Adult daughters' reports of breast cancer risk reduction and early detection advice received from their mothers: an exploratory study. Psychooncology 18:169-78 |
| Kelemen, Linda E; Pankratz, V Shane; Sellers, Thomas A et al. (2008) Age-specific trends in mammographic density: the Minnesota Breast Cancer Family Study. Am J Epidemiol 167:1027-36 |
| Myers, Cynthia D; Jacobsen, Paul B; Huang, Yifan et al. (2008) Familial and perceived risk of breast cancer in relation to use of complementary medicine. Cancer Epidemiol Biomarkers Prev 17:1527-34 |
| Olson, Janet E; Ingle, James N; Ma, Cynthia X et al. (2007) A comprehensive examination of CYP19 variation and risk of breast cancer using two haplotype-tagging approaches. Breast Cancer Res Treat 102:237-47 |
| Cox, Angela; Dunning, Alison M; Garcia-Closas, Montserrat et al. (2007) A common coding variant in CASP8 is associated with breast cancer risk. Nat Genet 39:352-8 |
| Vachon, Celine M; Sellers, Thomas A; Carlson, Erin E et al. (2007) Strong evidence of a genetic determinant for mammographic density, a major risk factor for breast cancer. Cancer Res 67:8412-8 |
| Olson, Janet E; Ma, Cynthia X; Pelleymounter, Linda L et al. (2007) A comprehensive examination of CYP19 variation and breast density. Cancer Epidemiol Biomarkers Prev 16:623-5 |
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