BRCA1 susceptibility markers and postmenopausal breast cancer: The Iowa Women's Health Study

Much research on early-onset breast cancer families has been performed and has shown that breast cancer in many of these families is linked to either BRCA1 or BRCA2, Fewer studies have examined the role of genetic predisposit ion in postmenopausal breast cancer. A nested case-control family study of breast cancer was conducted within the Iowa Women's Health Study, a populat ion-based prospective study of 41,836 postmenopausal women. Probands were 2 51 incident cases diagnosed between 1988 and 1989, Three-generation pedigre es were developed through mailed questionnaires. From this collection of pe digrees, thirteen were identified for more detailed genetic analysis. Sibli ng-pair linkage analyses were performed using polymorphic markers in candid ate regions in these 13 families with multiple cases of breast and other ca ncers, Four of the DNA markers are located on chromosome 17, and two of the se (D17S579 and THRA1) flank the BRCA1 locus. Significant evidence for link age to D17S579 was obtained in the total sample, in a model without inclusi on of covariates or age at onset (P = 0.005), and in a model adjusted for f ive measured covariates and for variable age at onset (P = 0.008), Complete sequencing of the BRCA1 gene in these families, including all intron/exon boundaries, failed to reveal any mutations in 24 women with breast cancer f rom the 13 families. These data suggest that in some families identified by postmenopausal breast cancer cases, breast cancer risk may be mediated by a gene (or genes) in the BRCA1 region, but not BRCA1 itself.