Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer Families

• DOI: 10.1086/301749
• Publication Date: 2002-07-26T18:45:21Z
• Authors: D. Ford; D.F. Easton; M. Stratton; S. Narod; D. Goldgar; P. Devilee; D.T. Bishop; B. Weber; G. Lenoir; J. Chang-Claude; H. Sobol; M.D. Teare; J. Struewing; A. Arason; S. Scherneck; J. Peto; T.R. Rebbeck; P. Tonin; S. Neuhausen; R. Barkardottir; J. Eyfjord; H. Lynch; B.A.J. Ponder; S.A. Gayther; J.M. Birch; A. Lindblom; D. Stoppa-Lyonnet; Y. Bignon; A. Borg; U. Hamann; N. Haites; R.J. Scott; C.M. Maugard; H. Vasen; S. Seitz; L.A. Cannon-Albright; A. Schofield; M. Zelada-Hedman
• Keywords: Penetrance; BRCA2 Protein

SummaryThe contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage mutation analysis in 237 families, each with at least four cases cancer, collected the Breast Cancer Linkage Consortium. Families were included without regard occurrence ovarian or other cancers. Overall, disease linked an estimated 52% 32% neither gene 16% (95% confidence interval [CI] 6%–28%), suggesting predisposition genes. The majority (81%) breast-ovarian families due BRCA1, most others (14%) BRCA2. Conversely, male female (76%). largest proportion (67%) genes found five only. These estimates not substantially affected either changing assumed penetrance model for including excluding data. Among those that tested one standard screening methods, mutations detected coding sequence splice sites 63% CI 51%–77%). sensitivity identical direct sequencing techniques. maximizing LOD score BRCA2-mutation over all possible functions. cumulative risk reached 28% 9%–44%) age 50 years 84% 43%–95%) 70 years. corresponding risks 0.4% 0%–1%) 27% 0%–47%) lifetime appears similar carriers, but there some suggestion a lower carriers <50 age.