A resource of breast cancer pedigrees has been developed through the ascertainment of nearly 100 unselected male and 250 female breast cancer patients as well as 620 patients selected for having a family history of the disease. Included in the resource are examples of defined clinico-genetic entities in each of which breast cancer is an integral component. These include the Li-Fraumeni syndrome, Muir's syndrome, Cowden's disease, breast-ovarian cancer, and site specific breast cancer. Because of their association with breast cancer, their being examples of dominantly inherited conditions, their relatively early ages at onset and involving indentifying lesions and tumors, these entities offer a unique opportunity for investigating the genetics of breast cancer within relatively homogeneous groups of pedigrees. The present intent is to utilize each of the entities in a linkage study in an attempt to localize each of the gene loci influencing breast cancer susceptibility to specific chromosome and/or to link them to genetic markers. Each entity will be evaluated for linkage between the susceptibility allele and an array of polymorphic marker loci determining cell surface antigens, plasma proteins, red cell enzymes, and immunoglobulin types. DNA markers comprised of cloned DNA sequences isolated from human tumors or tumor cell lines and viral oncogene probes will be added to the array during the coming year. Initial effort to date has been directed toward examining a previously reported linkage between a susceptibility allele for breast and ovarian cancer and the marker locus for glutamate pyruvate transaminase (GPT). This proposed linkage is being examined in 17 pedigrees. Preliminary analysis of 5 of the most complete of these pedigrees has provided evidence of small but positive lod scores with the GPT. After completion of sampling and analyses of the breast-ovarian pedigrees, effort will shift to analysis of 19 pedigrees with site-specific breast cancer. These will be followed by 10 pedigrees with the Li-Fraumeni syndrome, and last, those with Muir's syndrome and Cowden's disease, and those ascertained from among the families of unselected male and female breast cancer patients. This project should provide insight into the genetics of breast cancer and the organization of the human genome; it might also provide a means by which high risk individuals could be identified through linked markers prior to the onset of tumors.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA029614-04
Application #
3168795
Study Section
Epidemiology and Disease Control Subcommittee 3 (EDC)
Project Start
1982-03-01
Project End
1987-03-31
Budget Start
1985-04-01
Budget End
1986-03-31
Support Year
4
Fiscal Year
1985
Total Cost
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Type
Hospitals
DUNS #
001910777
City
Houston
State
TX
Country
United States
Zip Code
77030
Anderson, D E (1992) Familial versus sporadic breast cancer. Cancer 70:1740-6
Mars, W M; Genuardi, M; Tsihira, H et al. (1991) Genomic changes on the short arm of human chromosome 1 in breast cancer. Cancer Detect Prev 15:145-9
Genuardi, M; Tsihira, H; Anderson, D E et al. (1989) Distal deletion of chromosome Ip in ductal carcinoma of the breast. Am J Hum Genet 45:73-82
Anderson, D E; Badzioch, M D (1989) Combined effect of family history and reproductive factors on breast cancer risk. Cancer 63:349-53
Ferrell, R E; Anderson, D E; Chidambaram, A et al. (1989) A genetic linkage study of familial breast-ovarian cancer. Cancer Genet Cytogenet 38:241-8
Chidambaram, A; Chakravarti, A; Ferrell, R E et al. (1988) Estimating the age-at-onset function using life-table methods. Genet Epidemiol 5:255-63
Kamboh, M I; Ferrell, R E (1988) Genetic studies of low abundance human plasma proteins. VIII. Inherited structural variation in antithrombin III. Ann Hum Genet 52:17-24
Kamboh, M I; Ferrell, R E (1987) Human transferrin polymorphism. Hum Hered 37:65-81
Kamboh, M I; Ferrell, R E (1987) Genetic studies of low-abundance human plasma proteins. VII. Heterogeneity of the C1S subcomponent of the first complement component. J Immunogenet 14:231-8
Escallon, M H; Ferrell, R E; Kamboh, M I (1987) Genetic studies of low-abundance human plasma proteins. IV. Improved typing of alpha-1 acid glycoprotein (orosomucoid) by isoelectric focusing and immunoblotting. Hum Hered 37:294-9

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