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. 2002 Jan 22;99(2):827-31.
doi: 10.1073/pnas.012584499. Epub 2002 Jan 15.

Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium

Deborah Thompson  1 , Csilla I Szabo, Jon Mangion, Rogier A Oldenburg, Fabrice Odefrey, Sheila Seal, Rita Barfoot, Karin Kroeze-Jansema, Dawn Teare, Nazneen Rahman, Hélène Renard, Graham Mann, John L Hopper, Saundra S Buys, Irene L Andrulis, Ruby Senie, Mary B Daly, Dee West, Elaine A Ostrander, Ken Offit, Tamar Peretz, Ana Osorio, J Benitez, Katherine L Nathanson, Olga M Sinilnikova, Edith Olàh, Yves-Jean Bignon, Pablo Ruiz, Michael D Badzioch, Hans F A Vasen, Andrew P Futreal, Catherine M Phelan, Steven A Narod, Henry T Lynch, Bruce A J Ponder, Ros A Eeles, Hanne Meijers-Heijboer, Dominique Stoppa-Lyonnet, Fergus J Couch, Diana M Eccles, D Gareth Evans, Jenny Chang-Claude, Gilbert Lenoir, Barbara L Weber, Peter Devilee, Douglas F Easton, David E Goldgar, Michael R Stratton; KConFab Consortium
Affiliations

Evaluation of linkage of breast cancer to the putative BRCA3 locus on chromosome 13q21 in 128 multiple case families from the Breast Cancer Linkage Consortium

Deborah Thompson et al. Proc Natl Acad Sci U S A. .

Abstract

The known susceptibility genes for breast cancer, including BRCA1 and BRCA2, only account for a minority of the familial aggregation of the disease. A recent study of 77 multiple case breast cancer families from Scandinavia found evidence of linkage between the disease and polymorphic markers on chromosome 13q21. We have evaluated the contribution of this candidate "BRCA3" locus to breast cancer susceptibility in 128 high-risk breast cancer families of Western European ancestry with no identified BRCA1 or BRCA2 mutations. No evidence of linkage was found. The estimated proportion (alpha) of families linked to a susceptibility locus at D13S1308, the location estimated by Kainu et al. [(2000) Proc. Natl. Acad. Sci. USA 97, 9603-9608], was 0 (upper 95% confidence limit 0.13). Adjustment for possible bias due to selection of families on the basis of linkage evidence at BRCA2 did not materially alter this result (alpha = 0, upper 95% confidence limit 0.18). The proportion of linked families reported by Kainu et al. (0.65) is excluded with a high degree of confidence in our dataset [heterogeneity logarithm of odds (HLOD) at alpha = 0.65 was -11.0]. We conclude that, if a susceptibility gene does exist at this locus, it can only account for a small proportion of non-BRCA1/2 families with multiple cases of early-onset breast cancer.

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Figures

Figure 1
Figure 1
Multipoint LOD scores for the 128 families analyzed are shown graphically. The solid line represents scores obtained under the assumption of homogeneity; the dashed line assumes the proportion of linked families (α) to be 65%, as estimated by Kainu et al. (10); and the dotted line represents the 95% upper confidence interval (α = 0.13).
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