Cancer risks in two large breast cancer families linked to BRCA2 on chromosome 13q12-13.
Doug Easton,Linda Steele,P Fields,W. Ormiston,D. Averill,P A Daly,Ross McManus,Susan L. Neuhausen,D Ford,Richard Wooster,Lisa A. Cannon-Albright,Michael R. Stratton,David E. Goldgar +12 more
TLDR
The results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCa1.Abstract:
The penetrance of the BRCA2 gene on chromosome 13q12-13 has been estimated in two large, systematically ascertained, linked families, by use of a maximum-likelihood method to incorporate both cancer-incidence data and 13q marker typings in the families. The cumulative risk of breast cancer in female gene carriers was estimated to be 59.8% by age 50 years (95% confidence interval [95% CI] 25.9%-78.5%) and 79.5% by age 70 years (95% CI 28.9%-97.5%). The cumulative risk of breast cancer in male carriers was estimated to be 6.3% (95% CI 1.4%-25.6%) by age 70 years. There was no evidence of any risk difference between the two families. These results indicate that the lifetime breast cancer risk in BRCA2 carriers, for at least a subset of mutations, is comparable to that for BRCA1. A significant excess of ovarian cancer in gene carriers was observed (relative risk 17.69, based on three cases), but the absolute risk of ovarian cancer was less than that reported for BRCA1. Significant excesses of laryngeal cancer (relative risk 7.67, based on two possible carriers) and prostate cancer (relative risk 2.89, based on five possible carriers) were also observed. One case of ocular melanoma, as well as a second eye cancer of unspecified histology, occurred in obligate gene carriers.read more
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Journal ArticleDOI
Genetic Heterogeneity and Penetrance Analysis of the BRCA1 and BRCA2 Genes in Breast Cancer Families
D Ford,Douglas F. Easton,Michael R. Stratton,Steven A. Narod,David E. Goldgar,Peter Devilee,D. T. Bishop,Barbara L. Weber,Gilbert M. Lenoir,Jenny Chang-Claude,Hagay Sobol,M D Teare,Jeffery P. Struewing,Adalgeir Arason,Siegfried Scherneck,Julian Peto,Timothy R. Rebbeck,Patricia N. Tonin,Susan L. Neuhausen,Rosa B. Barkardottir,Jorunn E. Eyfjord,Henry T. Lynch,Bruce A.J. Ponder,Simon A. Gayther,J.M. Birch,Annika Lindblom,Dominique Stoppa-Lyonnet,Y. J. Bignon,Åke Borg,U Hamann,Neva E. Haites,Rodney J. Scott,Christine Maugard,Hans F. A. Vasen,Susanne Seitz,Lisa A. Cannon-Albright,Andrew Craig Schofield,Moraima Zelada-Hedman +37 more
TL;DR: The lifetime risk of breast cancer appears similar to the risk in BRCA1 carriers, but there was some suggestion of a lower risk in bRCA2 carriers <50 years of age.
Journal ArticleDOI
Cancer risks in BRCA2 mutation carriers
TL;DR: In addition to the large risks of breast and ovarian cancers, BRCA2 mutations may be associated with increased risks of several other cancers.
Journal ArticleDOI
Clinical Characteristics of Individuals With Germline Mutations in BRCA1 and BRCA2: Analysis of 10,000 Individuals
Thomas S. Frank,Amie M. Deffenbaugh,Julia Reid,Mark Hulick,Brian E. Ward,Beth Lingenfelter,Kathi L. Gumpper,Thomas Scholl,Sean V. Tavtigian,Dmitry Pruss,Gregory C. Critchfield +10 more
TL;DR: Specific features of personal and family history can be used to assess the likelihood of identifying a mutation in BRCA1 or BRCa2 in individuals tested in a clinical setting.
Journal ArticleDOI
Cancer Risks for BRCA1 and BRCA2 Mutation Carriers: Results From Prospective Analysis of EMBRACE
Nasim Mavaddat,Susan Peock,Debra Frost,Steve Ellis,Radka Platte,Elena Fineberg,D. Gareth Evans,Louise Izatt,Rosalind A. Eeles,Julian Adlard,Rosemarie Davidson,Diana Eccles,Trevor Cole,Jackie Cook,Carole Brewer,Marc Tischkowitz,Fiona Douglas,Shirley Hodgson,Lisa Walker,Mary Porteous,Patrick J. Morrison,Lucy Side,M. John Kennedy,C. E. Houghton,Alan Donaldson,Mark T. Rogers,Huw Dorkins,Zosia Miedzybrodzka,Helen Gregory,Jacqueline Eason,Julian Barwell,Emma McCann,Alex Murray,Antonis C. Antoniou,Douglas F. Easton +34 more
TL;DR: Prospective risk estimates for breast cancer, ovarian cancer, and contralateral breast cancer in a prospective series of mutation carriers confirm findings from retrospective studies that common breast cancer susceptibility alleles in combination are predictive of breast cancer risk for BRCA2 carriers.
Journal ArticleDOI
Determining Carrier Probabilities for Breast Cancer–Susceptibility Genes BRCA1 and BRCA2
TL;DR: A model for evaluating the probabilities that a woman is a carrier of a mutation of BRCA1 and BRCa2, on the basis of her family history of breast and ovarian cancer in first- and second-degree relatives is developed.
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