): BRCA1 and BRCA2 are clearly important determinants of breast cancer risk, but even within a family segregating a mutation, there is wide variability in the age-at-onset distribution. We hypothesize that differences in modifiable lifestyle factors influence this variability. Identification of factors associated with later age at onset may help inform approaches to risk reduction in individuals with a strong inherited predisposition to breast and/or ovarian cancer. A genetic study of breast cancer was conducted at the University of Minnesota using a consecutive series of patients between 1944 and 1952. We have successfully recontacted these families and extended the pedigrees to four- to five-generations. Detailed risk factor information has now been collected through telephone interviews, mailed questionnaires to assess anthropometrics and diet, mammography, and review of medical records and death certificates. These 426 breast cancer families include 260 with at least 2 affected individuals with breast or ovarian cancer, 132 of which contain 3 or more affected individuals. The 260 families will be screened for mutations in BRCA1 and BRCA2 using conformation sensitive gel electrophoresis (CSGE) and direct sequencing. In those families found to be segregating mutations, we will collect additional blood samples from other affected and unaffected members for mutation detection. Survival analysis using the Cox proportional hazards and accelerated failure time models will be carried out. Ample statistical power is available to detect gene x environment interactions as low as 1.75-fold. Given the wealth of risk factor data already collected on these families, we are in a unique position to identify how these factors modify expression and penetrance of the two major susceptibility genes for breast cancer in a well-characterized cohort of families. The results may help inform approaches to the primary prevention of cancer in these high-risk women.
| 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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