A genetic epidemiologic investigation of breast cancer in families with bilateral breast cancer. I. Segregation analysis.

A complex segregation analysis was conducted of breast cancer in 200 families with bilateral breast cancer. Results for two analyses are presented. The first analysis considered only premenopausal cases of breast cancer as affected. The results indicate that mendelian transmission of a single locus is not sufficient to explain the distribution of premenopausal breast cancer seen. A mixed model, i.e., a major locus plus other transmission (genetic and/or cultural), is necessary to explain the distribution. The second analysis added postmenopausal cases of breast cancer to the premenopausal ones, thus considering all breast cancer cases to be affected with the same disorder. The all-cases analysis is unable to reject a mixed model with no generation differences in heritability when tested against the general model, which allows for generation differences (i.e., the likelihoods for the two models were not significantly different). Approaches to studying etiologic heterogeneity in segregation analysis and results of other segregation analyses of breast cancer are presented.