CHROMOSOME-17Q LINKAGE STUDIES OF 18 UTAH BREAST-CANCER KINDREDS

In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD s cores greater than 1.0 for at least one of the marker loci. One of the se kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family reported to date. Among the kindre ds which appear unlinked to 17q were an early-onset breast cancer fami ly, a large breast-ovarian family, and a kindred with mixed age at ons et. Analysis of individual recombinants in the linked families localiz es the BRCA1 gene between THRA1 and D17S579 (Mfd188). A comparison of the Cancer and Steroid Hormone Study (CASH) model and a model which as sumes a rare dominant susceptibility locus with low penetrance and no phenocopies stresses the difficulties in assessing linkage if the assu mptions of the CASH model in terms of age at onset of breast cancer ar e not appropriate for the BRCA1 locus. A hypothetical breast cancer pe digree is used to calculate gene carrier probabilities under the CASH model, thereby illustrating some of our concerns regarding the use of this model to detect and exclude 17q linkage in breast cancer families .