Hereditary breast cancer (HBC) is considered to be a heterogeneous disorder with genetic transmission by an autosomal dominantly inherited, highly penetrant, cancer susceptibility gene(s). A large number of kindreds segregating this trait are currently under study by us. Recent advances in genetics, including improvements in the human genetic linkage map, and findings of linkage in several cancer susceptibility disorders, make linkage studies of HBC families possible and urgent. We propose a multicentered collaboration using extensive blood sample collection in a small but carefully selected set of highly informative HBC families (500 individuals in 8 families) to enable the most sophisticated molecular genetic and statistical methods, currently available, to be applied to the search for linkage. In tandem with blood collection for linkage studies, we will collect tumor specimens (slides and paraffin-embedded tumor blocks) from approximately 200 breast cancer-affected members of HBC and nonHBC. We will use the specimens to extend our pilot studies contrasting HBC and nonHBC breast cancers as clinicopathologically distinct subsets, with emphasis on tumor histology, mitotic grade, ploidy, and proliferation measured by flow cytometry. We will also create and maintain an archive of tumor specimens for future tumor marker studies which are not part of the present proposal but which will be targeted by findings in the linkage study. This effort harbors the potential for identifying the HBC gene(s) and extending knowledge of HBC's pathology so that knowledge of HBS's etiology and pathogenesis might be further elucidated. This achievement would have profound control implications.
| Marcus, J N; Watson, P; Page, D L et al. (1997) BRCA2 hereditary breast cancer pathophenotype. Breast Cancer Res Treat 44:275-7 |
| Marcus, J N; Watson, P; Page, D L et al. (1996) Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer 77:697-709 |
| Marcus, J N; Watson, P; Page, D L et al. (1994) Pathology and heredity of breast cancer in younger women. J Natl Cancer Inst Monogr :23-34 |
| Lynch, H T; Lynch, J; Conway, T et al. (1994) Psychological aspects of monitoring high risk women for breast cancer. Cancer 74:1184-92 |
| Lynch, H T; Watson, P; Conway, T A et al. (1993) DNA screening for breast/ovarian cancer susceptibility based on linked markers. A family study. Arch Intern Med 153:1979-87 |
| Feunteun, J; Narod, S A; Lynch, H T et al. (1993) A breast-ovarian cancer susceptibility gene maps to chromosome 17q21. Am J Hum Genet 52:736-42 |
| Lynch, H T; Watson, P; Lynch, J F et al. (1993) Hereditary ovarian cancer. Heterogeneity in age at onset. Cancer 71:573-81 |
| Lynch, H T; Lynch, J F (1992) Hereditary ovarian carcinoma. Hematol Oncol Clin North Am 6:783-811 |
| Thor, A D; Moore DH, I I; Edgerton, S M et al. (1992) Accumulation of p53 tumor suppressor gene protein: an independent marker of prognosis in breast cancers. J Natl Cancer Inst 84:845-55 |
| Bewtra, C; Watson, P; Conway, T et al. (1992) Hereditary ovarian cancer: a clinicopathological study. Int J Gynecol Pathol 11:180-7 |
Showing the most recent 10 out of 18 publications
