We propose to evaluate the genetic component in the etiology of breast cancer with segregation and linkage analyses. Index cases will be cases with early (<50 years of age) bilateral breat cancer who are currently participating in a study by the USC school of medicine. We will administer a more detailed geneology questionnaire to all index cases, confirm the diagnoses of all possible cases of breast cancer among relatives and obtain one blood sample from each member of multiplex nuclear families. Twenty- eight genetic makers will be determined in the laboratory of Dr. Robert Sparkes at UCLA. By the end of the study, we anticipate having approximately 211 index cases and 50 multiplex families. Segregation analysis will be conducted to test whether or not the distribution of breast cancer in families is consistent with a breast cancer susceptibility gene, and, if so which model best fits our data. We will use an extension of Morton and Maclean's mixed model (MIXMOD) that allows for incomplete ascertainment, selection of certain kinds of multiplex pedigrees, and variable ages of onset. We will then test for linkage between a presumed breast cancer susceptibility gene and 28 genetic marker loci. We will utilize the program LIPED, which can incorporate into the analysis different recombination values in males and females, and incomplete penetrance, which includes age of onset corrections.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA036387-09
Application #
3173956
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1984-01-01
Project End
1993-04-30
Budget Start
1992-06-03
Budget End
1993-04-30
Support Year
9
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Type
Schools of Public Health
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Haile, R W; Goldstein, A M; Weeks, D E et al. (1990) Genetic epidemiology of bilateral breast cancer: a linkage analysis using the affected-pedigree-member method. Genet Epidemiol 7:47-55
Goldstein, A M; Haile, R W; Hodge, S E et al. (1988) Possible heterogeneity in the segregation pattern of breast cancer in families with bilateral breast cancer. Genet Epidemiol 5:121-33
Goldstein, A M; Haile, R W; Marazita, M L et al. (1987) A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. I. Segregation analysis. J Natl Cancer Inst 78:911-8