Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.

2.50
Hdl Handle:
http://hdl.handle.net/10541/91923
Title:
Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.
Authors:
Ford, D; Easton, D F; Stratton, M; Narod, S; Goldgar, D; Devilee, P; Bishop, D T; Weber, B; Lenoir, G; Chang-Claude, J; Sobol, H; Teare, M Dawn; Struewing, J; Arason, A; Scherneck, S; Peto, J; Rebbeck, T R; Tonin, P; Neuhausen, S; Barkardottir, R B; Eyfjord, J; Lynch, H; Ponder, B A; Gayther, S A; Zelada-Hedman, M; Birch, Jillian M
Abstract:
The contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. 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.
Affiliation:
Section of Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.
Citation:
Genetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. 1998, 62 (3):676-89 Am. J. Hum. Genet.
Journal:
American Journal of Human Genetics
Issue Date:
Mar-1998
URI:
http://hdl.handle.net/10541/91923
DOI:
10.1086/301749
PubMed ID:
9497246
Type:
Article
Language:
en
ISSN:
0002-9297
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorFord, Den
dc.contributor.authorEaston, D Fen
dc.contributor.authorStratton, Men
dc.contributor.authorNarod, Sen
dc.contributor.authorGoldgar, Den
dc.contributor.authorDevilee, Pen
dc.contributor.authorBishop, D Ten
dc.contributor.authorWeber, Ben
dc.contributor.authorLenoir, Gen
dc.contributor.authorChang-Claude, Jen
dc.contributor.authorSobol, Hen
dc.contributor.authorTeare, M Dawnen
dc.contributor.authorStruewing, Jen
dc.contributor.authorArason, Aen
dc.contributor.authorScherneck, Sen
dc.contributor.authorPeto, Jen
dc.contributor.authorRebbeck, T Ren
dc.contributor.authorTonin, Pen
dc.contributor.authorNeuhausen, Sen
dc.contributor.authorBarkardottir, R Ben
dc.contributor.authorEyfjord, Jen
dc.contributor.authorLynch, Hen
dc.contributor.authorPonder, B Aen
dc.contributor.authorGayther, S Aen
dc.contributor.authorZelada-Hedman, Men
dc.contributor.authorBirch, Jillian Men
dc.date.accessioned2010-02-12T11:50:36Z-
dc.date.available2010-02-12T11:50:36Z-
dc.date.issued1998-03-
dc.identifier.citationGenetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium. 1998, 62 (3):676-89 Am. J. Hum. Genet.en
dc.identifier.issn0002-9297-
dc.identifier.pmid9497246-
dc.identifier.doi10.1086/301749-
dc.identifier.urihttp://hdl.handle.net/10541/91923-
dc.description.abstractThe contribution of BRCA1 and BRCA2 to inherited breast cancer was assessed by linkage and mutation analysis in 237 families, each with at least four cases of breast cancer, collected by the Breast Cancer Linkage Consortium. Families were included without regard to the occurrence of ovarian or other cancers. Overall, disease was linked to BRCA1 in an estimated 52% of families, to BRCA2 in 32% of families, and to neither gene in 16% (95% confidence interval [CI] 6%-28%), suggesting other predisposition genes. The majority (81%) of the breast-ovarian cancer families were due to BRCA1, with most others (14%) due to BRCA2. Conversely, the majority of families with male and female breast cancer were due to BRCA2 (76%). The largest proportion (67%) of families due to other genes was found in families with four or five cases of female breast cancer only. These estimates were not substantially affected either by changing the assumed penetrance model for BRCA1 or by including or excluding BRCA1 mutation data. Among those families with disease due to BRCA1 that were tested by one of the standard screening methods, mutations were detected in the coding sequence or splice sites in an estimated 63% (95% CI 51%-77%). The estimated sensitivity was identical for direct sequencing and other techniques. The penetrance of BRCA2 was estimated by maximizing the LOD score in BRCA2-mutation families, over all possible penetrance functions. The estimated cumulative risk of breast cancer reached 28% (95% CI 9%-44%) by age 50 years and 84% (95% CI 43%-95%) by age 70 years. The corresponding ovarian cancer risks were 0.4% (95% CI 0%-1%) by age 50 years and 27% (95% CI 0%-47%) by age 70 years. 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.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectCancer Proteinsen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshBRCA2 Protein-
dc.subject.meshBreast Neoplasms-
dc.subject.meshFemale-
dc.subject.meshGenes, BRCA1-
dc.subject.meshGenetic Heterogeneity-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshHeterozygote Detection-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshMutation-
dc.subject.meshNeoplasm Proteins-
dc.subject.meshTranscription Factors-
dc.titleGenetic heterogeneity and penetrance analysis of the BRCA1 and BRCA2 genes in breast cancer families. The Breast Cancer Linkage Consortium.en
dc.typeArticleen
dc.contributor.departmentSection of Epidemiology, Institute of Cancer Research, Sutton, United Kingdom.en
dc.identifier.journalAmerican Journal of Human Geneticsen

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