Show simple item record

dc.contributor.authorFord, D
dc.contributor.authorEaston, D F
dc.contributor.authorStratton, M
dc.contributor.authorNarod, S
dc.contributor.authorGoldgar, D
dc.contributor.authorDevilee, P
dc.contributor.authorBishop, D T
dc.contributor.authorWeber, B
dc.contributor.authorLenoir, G
dc.contributor.authorChang-Claude, J
dc.contributor.authorSobol, H
dc.contributor.authorTeare, M Dawn
dc.contributor.authorStruewing, J
dc.contributor.authorArason, A
dc.contributor.authorScherneck, S
dc.contributor.authorPeto, J
dc.contributor.authorRebbeck, T R
dc.contributor.authorTonin, P
dc.contributor.authorNeuhausen, S
dc.contributor.authorBarkardottir, R B
dc.contributor.authorEyfjord, J
dc.contributor.authorLynch, H
dc.contributor.authorPonder, B A
dc.contributor.authorGayther, S A
dc.contributor.authorZelada-Hedman, M
dc.contributor.authorBirch, Jillian M
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.
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
html.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.


This item appears in the following Collection(s)

Show simple item record