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Por favor, use este identificador para citar o enlazar a este item: http://hdl.handle.net/10261/116985
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dc.contributor.authorRebbeck, Timothy R.-
dc.contributor.authorOsorio, Ana-
dc.contributor.authorBenitez, Javier-
dc.contributor.authorTejada, María Isabel-
dc.contributor.authorDurán, Mercedes-
dc.contributor.authorHoya, Miguel de la-
dc.contributor.authorDíez, Orland-
dc.contributor.authorBlanco, Ignacio-
dc.date.accessioned2015-06-22T11:52:04Z-
dc.date.available2015-06-22T11:52:04Z-
dc.date.issued2015-
dc.identifierdoi: 10.1001/jama.2014.5985-
dc.identifierissn: 0098-7484-
dc.identifiere-issn: 1538-3598-
dc.identifier.citationJournal of the American Medical Association 313(13): 1347-1361 (2015)-
dc.identifier.urihttp://hdl.handle.net/10261/116985-
dc.descriptionCIMBA Consortium et al.-
dc.descriptionPMID: 25849179-
dc.description.abstract[Importance]: Limited information about the relationship between specific mutations in BRCA1 or BRCA2 (BRCA1/2) and cancer risk exists. [Objective]: To identify mutation-specific cancer risks for carriers of BRCA1/2. [Design, Setting, and Participants]: Observational study ofwomen whowere ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated BRCA1 or BRCA2 mutations. The international sample comprised 19 581 carriers of BRCA1 mutations and 11 900 carriers of BRCA2 mutations from 55 centers in 33 countries on 6 continents.We estimated hazard ratios for breast and ovarian cancer based on mutation type, function, and nucleotide position.We also estimated RHR, the ratio of breast vs ovarian cancer hazard ratios. A value of RHR greater than 1 indicated elevated breast cancer risk; a value of RHR less than 1 indicated elevated ovarian cancer risk. [Exposures]: Mutations of BRCA1 or BRCA2. [Main Outcomes and Measures]: Breast and ovarian cancer risks. [Results]: Among BRCA1 mutation carriers, 9052 women (46%) were diagnosed with breast cancer, 2317 (12%) with ovarian cancer, 1041 (5%) with breast and ovarian cancer, and 7171 (37%) without cancer. Among BRCA2 mutation carriers, 6180 women (52%) were diagnosed with breast cancer, 682 (6%) with ovarian cancer, 272 (2%) with breast and ovarian cancer, and 4766 (40%) without cancer. In BRCA1, we identified 3 breast cancer cluster regions (BCCRs) located at c.179 to c.505 (BCCR1; RHR = 1.46; 95%CI, 1.22-1.74; P = 2 × 10-6), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95%CI, 1.01-1.78; P = .04), and c. 5261 to c.5563 (BCCR2', RHR = 1.38; 95%CI, 1.22-1.55; P = 6 × 10-9).We also identified an ovarian cancer cluster region (OCCR) from c.1380 to c.4062 (approximately exon 11) with RHR = 0.62 (95%CI, 0.56-0.70; P = 9 × 10<sup>-17</sup>). In BRCA2, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95%CI, 1.06-2.78; P = .03), c.772 to c.1806 (BCCR1'; RHR = 1.63; 95%CI, 1.10-2.40; P = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95%CI, 1.69-3.16; P = .00002).We also identified 3 OCCRs: the first (OCCR1) spanned c.3249 to c.5681 that was adjacent to c.5946delT (6174delT; RHR = 0.51; 95%CI, 0.44-0.60; P = 6 × 10<sup>-17</sup>). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95%CI, 0.41-0.80; P = .001). Mutations conferring nonsense-mediated decay were associated with differential breast or ovarian cancer risks and an earlier age of breast cancer diagnosis for both BRCA1 and BRCA2 mutation carriers. [Conclusions and Relevance]: Breast and ovarian cancer risks varied by type and location of BRCA1/2 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of BRCA1 and BRCA2 mutations.-
dc.description.sponsorshipDr Antoniou and the CIMBA data management are funded by Cancer Research UK. Dr Easton is a Principal Research Fellow of Cancer Research UK. Dr Rebbeck is supported by R01-CA083855, R01-CA102776, and P50-CA083638 from the National Institutes of Health (NIH). Dr Rebbeck, Dr Nathanson, Ms Friebel, and Dr Domchek are supported by the Basser Research Center at the University of Pennsylvania. Dr Nathanson is supported by the Breast Cancer Research Foundation. Drs Domchek and Nathanson are supported by the Rooney Family Foundation. Dr Poppe is supported by R01-CA112520 from NIH. Cancer Research UK provided financial support for this work. Dr Antoniou is a Senior Cancer Research UK Cancer Research Fellow. Dr Phillips is a National Breast Cancer Foundation (Australia) Practitioner Fellow.-
dc.publisherAmerican Medical Association-
dc.relation.isversionofPostprint-
dc.rightsopenAccess-
dc.titleAssociation of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer-
dc.typeartículo-
dc.identifier.doi10.1001/jama.2014.5985-
dc.relation.publisherversionhttps://doi.org/10.1001/jama.2014.5985-
dc.date.updated2015-06-22T11:52:04Z-
dc.description.versionPeer Reviewed-
dc.language.rfc3066eng-
dc.contributor.funderCancer Research UK-
dc.contributor.funderNational Institutes of Health (US)-
dc.contributor.funderUniversity of Pennsylvania-
dc.contributor.funderBreast Cancer Research Foundation-
dc.relation.csicSí-
dc.identifier.funderhttp://dx.doi.org/10.13039/501100000289es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100000002es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100006920es_ES
dc.identifier.funderhttp://dx.doi.org/10.13039/100001006es_ES
dc.identifier.pmid25849179-
dc.type.coarhttp://purl.org/coar/resource_type/c_6501es_ES
item.fulltextWith Fulltext-
item.openairecristypehttp://purl.org/coar/resource_type/c_18cf-
item.cerifentitytypePublications-
item.openairetypeartículo-
item.grantfulltextopen-
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