Family resources and specific laboratory techniques for studying hereditary breast cancer will be developed. Breast cancer patients aged 20-29 will be ascertained through the Cancer Surveillance Program of Orange County (CSPOC) database of cancer cases for 1984-1992. Previous studies indicate that 36% of these patients will have hereditary breast cancer. Family history information through first-cousins will be obtained from each proband. Segregation analysis will be applied to these data to estimate the frequency of hereditary breast cancer, and the penetrance in gene carriers. Selected pedigrees will be extended as far as possible, in order to study gene linkage of breast cancer including p53, D17S74, D17S5 and D17S4. The laboratory techniques needed to combine the linkage studies with loss of heterozygosity (LOH) studies in tumor tissue from affected family members will be developed. Many of these procedures have already been developed in one or both of the two collaborating laboratories; however special issues must be addressed in order to apply the techniques to studies of hereditary breast cancer. We expect to obtain family history data from about 80 cases, and to identify at least 10 families for gene linkage studies. The family resource and laboratory techniques are critical for future studies of hereditary breast cancer which are currently being planned. Specifically, we will eventually use the family resource and laboratory techniques in future studies in order to: (1) map the location of inherited breast cancer predisposing genes; (2) characterize specific mutations; (3) study the interrelationships between genotype, environmental and clinical variables.
Barker, D F; Almeida, E R; Casey, G et al. (1996) BRCA1 R841W: a strong candidate for a common mutation with moderate phenotype. Genet Epidemiol 13:595-604 |
Barker, D F; Liu, X; Almeida, E R (1996) The BRCA1 and 1A1.3B promoters are parallel elements of a genomic duplication at 17q21. Genomics 38:215-22 |
Plummer, S J; Santibanez-Koref, M; Kurosaki, T et al. (1994) A germline 2.35 kb deletion of p53 genomic DNA creating a specific loss of the oligomerization domain inherited in a Li-Fraumeni syndrome family. Oncogene 9:3273-80 |
Nechiporuk, A; Fain, P; Kort, E et al. (1993) Linkage of familial Alzheimer disease to chromosome 14 in two large early-onset pedigrees: effects of marker allele frequencies on lod scores. Am J Med Genet 48:63-6 |