Abstract
We have analyzed, by a combination of mutation and linkage analysis, the genetic basis of 22 breast cancer families in which at least 4 cases of either breast cancer diagnosed under the age of 60 or ovarian cancer had occurred. Chain-terminating mutations in BRCA1 were evidenced in 6 families, and posterior probabilities of <0.90 of being linked to BRCA1 in 3. The breast versus ovarian cancer ratio in these 9 families was approximately 2:1. Among the remaining 13 families, significant linkage to markers flanking BRCA2 was established in the admixture test with a maximum multipoint lod score of 3.38, but there was no statistical evidence for genetic heterogeneity. The breast:ovarian cancer ratio in these families was 7:1, suggesting BRCA2 confers a much lower risk for ovarian cancer than does BRCA1. These results suggest that BRCA2 will explain a significant proportion of hereditary breast cancer in the Netherlands, and, together with BRCA1, account for the majority of all high-risk families.
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Acknowledgements
The authors thank Mrs. I. van Leeuwen for blood sampling, and Dr. D.F. Easton for statistical support. This work was supported by a grant from the Dutch Cancer Society and is part of ongoing studies within the Breast Cancer Linkage Consortium, supported by BIOMEDl-grant PL920890.
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Peelen, T., Cornelis, R.S., van Vliet, M. et al. The Majority of 22 Dutch High-Risk Breast Cancer Families Are due to Either BRCA1 or BRCA2. Eur J Hum Genet 4, 225–230 (1996). https://doi.org/10.1159/000472203
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DOI: https://doi.org/10.1159/000472203
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