Prevalence of BRCA1 and BRCA2 Gene Mutations in Patients With Early-Onset Breast Cancer
Julian Peto,N. Collins,Rita Barfoot,Sheila Seal,William H. Warren,Nazneen Rahman,Douglas F. Easton,Christopher H. Evans,Judith Deacon,Michael R. Stratton +9 more
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TLDR
Mutations in the BRCA1 and BRCa2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.Abstract:
Background Mutations in the BRCA1 and BRCA2 genes are found in most families with cases of both breast and ovarian cancer or with many cases of early-onset breast cancer. However, in an outbred population, the prevalence of BRCA1 and BRCA2 mutations in patients with breast cancer who were unselected for a family history of this disease has not been determined. Methods Mutations in the BRCA1 and BRCA2 genes were detected in blood samples from two population-based series of young patients with breast cancer from Britain. Results Mutations were detected in 15 (5.9%) of 254 women diagnosed with breast cancer before age 36 years (nine [3.5%] in BRCA1 and six [2.4%] in BRCA2) and in 15 (4.1%) of 363 women diagnosed from ages 36 through 45 years (seven [1.9%] in BRCA1 and eight [2.2%] in BRCA2). Eleven percent (six of 55) of patients with a first-degree relative who developed ovarian cancer or breast cancer by age 60 years were mutation carriers, compared with 45% (five of 11) of patients with two or more affected first- or second-degree relatives. The standardized incidence ratio for breast cancer in mothers and sisters was 365 (five observed and 1.37 expected) for 30 mutation carriers and 199 (64 observed and 32.13 expected) for 587 noncarriers. If we assume recent penetrance estimates, the respective proportions of BRCA1 and BRCA2 mutation carriers are 3.1% and 3.0%, respectively, of patients with breast cancer who are younger than age 50 years, 0.49% and 0.84% of patients with breast cancer who are age 50 years or older, and 0.11% and 0.12% of women in the general population. Conclusions Mutations in the BRCA1 and BRCA2 genes make approximately equal contributions to early-onset breast cancer in Britain and account for a small proportion of the familial risk of breast cancer.read more
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Journal ArticleDOI
Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies
Antonis C. Antoniou,Paul D.P. Pharoah,Steven A. Narod,Harvey A. Risch,Jorunn E. Eyfjord,John L. Hopper,Niklas Loman,Håkan Olsson,Oskar T. Johannsson,Åke Borg,Barbara Pasini,Paolo Radice,Siranoush Manoukian,Diana Eccles,Nelson L.S. Tang,E. Olah,Hoda Anton-Culver,Ellen Warner,Jan Lubinski,Jacek Gronwald,Bohdan Górski,Hrafn Tulinius,Steinunn Thorlacius,Hannaleena Eerola,Heli Nevanlinna,Kirsi Syrjäkoski,Olli Kallioniemi,Deborah J. Thompson,Christopher H. Evans,Julian Peto,Julian Peto,Fiona Lalloo,D G R Evans,Douglas F. Easton +33 more
TL;DR: Risks in carriers were higher when based on index breast cancer cases diagnosed at <35 years of age and for variation in risk by mutation position for both genes, and some evidence for a reduction in risk in women from earlier birth cohorts is found.
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Epidemiology of breast cancer.
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A breast cancer prediction model incorporating familial and personal risk factors.
TL;DR: An Erratum has been published for this article in Statistics in Medicine 2005; 24(1):156.
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The personal and clinical utility of polygenic risk scores.
TL;DR: The authors review recent studies that have demonstrated the utility of polygenic risk scores for disease risk stratification and their potential impact on early disease detection, prevention, therapeutic intervention and life planning.
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Low-penetrance susceptibility to breast cancer due to CHEK2(*)1100delC in noncarriers of BRCA1 or BRCA2 mutations
Hanne Meijers-Heijboer,Ans M.W. van den Ouweland,Jan Klijn,Marijke Wasielewski,Anja de Snoo,Rogier A. Oldenburg,Antoinette Hollestelle,M.M.J. Houben,Ellen Crepin,Monique M. van Veghel-Plandsoen,Fons Elstrodt,Cornelia M. van Duijn,C.C.M. Bartels,Carel Meijers,Mieke Schutte,Lesley McGuffog,Deborah J. Thompson,Douglas F. Easton,Nayanta Sodha,Sheila Seal,Rita Barfoot,Jon Mangion,Jenny Chang-Claude,Diana Eccles,Rosalind A. Eeles,D. Gareth Evans,Richard S. Houlston,Victoria Murday,Steven A. Narod,Tamara Peretz,Julian Peto,Julian Peto,Catherine M. Phelan,Hong Xiang Zhang,Csilla Szabo,Peter Devilee,David E. Goldgar,P. Andrew Futreal,Katherine L. Nathanson,Barbara L. Weber,Nazneen Rahman,Michael R. Stratton,Michael R. Stratton +42 more
TL;DR: The biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCa2 mutations, which is consistent with participation of the encoded proteins in the same pathway.
References
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A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1
Yoshio Miki,Jeff Swensen,Donna M Shattuck-Eidens,P. Andrew Futreal,Keith D Harshman,Sean V. Tavtigian,Qingyun Liu,Charles Cochran,L. Michelle Bennett,Wei Ding,Russell Bell,Judith Rosenthal,Charles E. Hussey,Thanh Tran,Melody McClure,Cheryl Frye,Tom Hattier,Robert Phelps,Astrid Haugen-Strano,Harold Katcher,Kazuko Yakumo,Zahra Gholami,Daniel Shaffer,Steven Stone,Steven Bayer,Christian Wray,Robert Bogden,Priya Dayananth,John R. Ward,Patricia N. Tonin,Steven A. Narod,Pam K. Bristow,Frank H. Norris,Leah M. Helvering,Paul Morrison,Paul Robert Rosteck,Mei Lai,J. Carl Barrett,Cathryn M. Lewis,Susan L. Neuhausen,Lisa A. Cannon-Albright,David E. Goldgar,Roger W. Wiseman,Alexander Kamb,Mark H. Skolnick +44 more
TL;DR: A strong candidate for the 17q-linked BRCA1 gene, which influences susceptibility to breast and ovarian cancer, has been identified by positional cloning methods.
Journal ArticleDOI
Identification of the breast cancer susceptibility gene BRCA2
Richard Wooster,Graham R. Bignell,Johnathan M. Lancaster,Sally Swift,Sheila Seal,Jonathon Mangion,N. Collins,Simon G. Gregory,Curtis Gumbs,Gos Micklem +9 more
TL;DR: The identification of a gene in which six different germline mutations in breast cancer families that are likely to be due to BRCA2 are detected, and results indicate that this is the BRC a2 gene.
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
Linkage of early-onset familial breast cancer to chromosome 17q21
TL;DR: Ch Chromosome 17q21 appears to be the locale of a gene for inherited susceptibility to breast cancer in families with early-onset disease, and genetic analysis yields a lod score of 5.98 for linkage of breast cancer susceptibility to D17S74 in early-ONSet families and negative lod scores in familiesWith late-onsets disease.
Journal ArticleDOI
The Risk of Cancer Associated with Specific Mutations of BRCA1 and BRCA2 among Ashkenazi Jews
Jeffery P. Struewing,Patricia Hartge,Sholom Wacholder,Sonya M. Baker,Martha Berlin,Mary McAdams,Michelle M. Timmerman,Lawrence C. Brody,Margaret A. Tucker +8 more
TL;DR: The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families.
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