Linkage heterogeneity among 59 Dutch hereditary breast cancer families
- Univ. of Leiden (Netherlands); and others
We have investigated 59 Dutch kindreds with at least three first-degree relatives with breast and/or ovarian cancer for linkage to BRCA1 on 17q12-q21, using at least 4 microsatellite markers flanking BRCA1 on either side. Assuming no heterogeneity, the overall multipoint lod score in this group of families was -7.59. A marked clustering of lod scores >0.5 was observed among the 13 families with a mean age of onset lower than 45 (total lod score: +3.36). Among the 8 kindreds with a mean age of onset lower than 45 and {ge}3 cases diagnosed under 45, the lod score was +4.43. Interestingly, most of the evidence against linkage was found in 17 families with a mean age of onset between 45 and 54 (total lod score of -8.72). It was estimated that 28% of the breast-only families might be caused by BRCA1. Over the 16 breast-ovarian cancer families a lod score of -3.78 was obtained under homogeneity. The highest lod score was +0.57, assuming heterogeneity with 33% of the families being linked to BRCA1. One family gave a multipoint lod score of -2.01 and thereby satisfies the conventional criterion of an unlinked family. Our results support the conclusions from earlier work by others, namely that BRCA1 predisposes particularly to early-onset breast cancer. The proportion of breast-ovarian cancer families we found linked to BRCA1 is much lower than that found by the Breast Cancer Linkage Consortium. This might be caused by the single unlinked family against an insufficient number of families able to give conclusive positive lod scores.
- OSTI ID:
- 133488
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-0216
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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