Genetic Analysis of Mammographic Breast Density in Adult Women: Evidence of a Gene Effect

The appearance of the female breast viewed by mammography varies considerably from one individual to another because of underlying differences in the relative proportions of fat, connective tissue, and glandular epithelium that combine to create a characteristic pattern of breast density. An association between mammographic patterns and family history of breast cancer has previously been reported. However, this association has not been found in all studies, and few data are available on possible genetic components contributing to mammographic breast density. Our purpose was to estimate familial correlations and perform complex genetic segregation analyses to test the hypothesis that the transmission of a major gene influences mammographic breast density. As part of a cohort study (initiated in 1944) of families with a history of breast cancer, the probands' female relatives who were older than 40 years were asked to obtain a routine mammogram. The mammograms of 1370 women from 258 independent families were analyzed. The fraction of the breast volume occupied by radiographically dense tissue was estimated visually from video displays of left or right mediolateral oblique views by one radiologist experienced in mammography who had no knowledge of individual relationships to the probands. Data on breast cancer risk factors were obtained through telephone interviews and mailed questionnaires. Unadjusted and adjusted familial correlations in breast density were calculated, and complex genetic segregation analyses were performed. Sister-sister correlations in breast density (unadjusted and adjusted for age and either body mass index, menopausal status, hormone replacement therapy, waist-to-hip ratio, number of live births, alcohol consumption, or cigarette smoking status) were all statistically significant (r = .16-.27; all P