AustralieFrV1, Pmc, Corpus, bibRecord, 001F42

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Identifieur interne : 001F42 ( Pmc/Corpus ); précédent : 001F41; suivant : 001F43

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Auteurs : Timothy R. Rebbeck ; Nandita Mitra ; Fei Wan ; Olga M. Sinilnikova ; Sue Healey ; Lesley Mcguffog ; Sylvie Mazoyer ; Georgia Chenevix-Trench ; Douglas F. Easton ; Antonis C. Antoniou ; Katherine L. Nathanson

Source :

JAMA [ 0098-7484 ] ; 2015.

RBID : PMC:4537700

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 of women who were 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 (BCCR23, 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 × 10⁻¹⁷). 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 (BCCR13; 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 × 10⁻¹⁷). 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.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537700

DOI: 10.1001/jama.2014.5985
PubMed: 25849179
PubMed Central: 4537700

Links to Exploration step

PMC:4537700

Le document en format XML

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 and <italic>BRCA2</italic>
 Mutations With Risk of Breast and Ovarian Cancer</title>
<author><name sortKey="Rebbeck, Timothy R" sort="Rebbeck, Timothy R" uniqKey="Rebbeck T" first="Timothy R." last="Rebbeck">Timothy R. Rebbeck</name>
</author>
<author><name sortKey="Mitra, Nandita" sort="Mitra, Nandita" uniqKey="Mitra N" first="Nandita" last="Mitra">Nandita Mitra</name>
</author>
<author><name sortKey="Wan, Fei" sort="Wan, Fei" uniqKey="Wan F" first="Fei" last="Wan">Fei Wan</name>
</author>
<author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M." last="Sinilnikova">Olga M. Sinilnikova</name>
</author>
<author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name>
</author>
<author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name>
</author>
<author><name sortKey="Mazoyer, Sylvie" sort="Mazoyer, Sylvie" uniqKey="Mazoyer S" first="Sylvie" last="Mazoyer">Sylvie Mazoyer</name>
</author>
<author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name>
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<author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name>
</author>
<author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C." last="Antoniou">Antonis C. Antoniou</name>
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<author><name sortKey="Nathanson, Katherine L" sort="Nathanson, Katherine L" uniqKey="Nathanson K" first="Katherine L." last="Nathanson">Katherine L. Nathanson</name>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Association of Type and Location of <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 Mutations With Risk of Breast and Ovarian Cancer</title>
<author><name sortKey="Rebbeck, Timothy R" sort="Rebbeck, Timothy R" uniqKey="Rebbeck T" first="Timothy R." last="Rebbeck">Timothy R. Rebbeck</name>
</author>
<author><name sortKey="Mitra, Nandita" sort="Mitra, Nandita" uniqKey="Mitra N" first="Nandita" last="Mitra">Nandita Mitra</name>
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<author><name sortKey="Wan, Fei" sort="Wan, Fei" uniqKey="Wan F" first="Fei" last="Wan">Fei Wan</name>
</author>
<author><name sortKey="Sinilnikova, Olga M" sort="Sinilnikova, Olga M" uniqKey="Sinilnikova O" first="Olga M." last="Sinilnikova">Olga M. Sinilnikova</name>
</author>
<author><name sortKey="Healey, Sue" sort="Healey, Sue" uniqKey="Healey S" first="Sue" last="Healey">Sue Healey</name>
</author>
<author><name sortKey="Mcguffog, Lesley" sort="Mcguffog, Lesley" uniqKey="Mcguffog L" first="Lesley" last="Mcguffog">Lesley Mcguffog</name>
</author>
<author><name sortKey="Mazoyer, Sylvie" sort="Mazoyer, Sylvie" uniqKey="Mazoyer S" first="Sylvie" last="Mazoyer">Sylvie Mazoyer</name>
</author>
<author><name sortKey="Chenevix Trench, Georgia" sort="Chenevix Trench, Georgia" uniqKey="Chenevix Trench G" first="Georgia" last="Chenevix-Trench">Georgia Chenevix-Trench</name>
</author>
<author><name sortKey="Easton, Douglas F" sort="Easton, Douglas F" uniqKey="Easton D" first="Douglas F." last="Easton">Douglas F. Easton</name>
</author>
<author><name sortKey="Antoniou, Antonis C" sort="Antoniou, Antonis C" uniqKey="Antoniou A" first="Antonis C." last="Antoniou">Antonis C. Antoniou</name>
</author>
<author><name sortKey="Nathanson, Katherine L" sort="Nathanson, Katherine L" uniqKey="Nathanson K" first="Katherine L." last="Nathanson">Katherine L. Nathanson</name>
</author>
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<series><title level="j">JAMA</title>
<idno type="ISSN">0098-7484</idno>
<idno type="eISSN">1538-3598</idno>
<imprint><date when="2015">2015</date>
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<front><div type="abstract" xml:lang="en"><sec id="S1"><title>IMPORTANCE</title>
<p id="P1">Limited information about the relationship between specific mutations in <italic>BRCA1</italic>
 or <italic>BRCA2</italic>
 (<italic>BRCA1/2</italic>
) and cancer risk exists.</p>
</sec>
<sec id="S2"><title>OBJECTIVE</title>
<p id="P2">To identify mutation-specific cancer risks for carriers of <italic>BRCA1/2</italic>
.</p>
</sec>
<sec id="S3"><title>DESIGN, SETTING, AND PARTICIPANTS</title>
<p id="P3">Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated <italic>BRCA1</italic>
 or <italic>BRCA2</italic>
 mutations. The international sample comprised 19 581 carriers of <italic>BRCA1</italic>
 mutations and 11 900 carriers of <italic>BRCA2</italic>
 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.</p>
</sec>
<sec id="S4"><title>EXPOSURES</title>
<p id="P4">Mutations of <italic>BRCA1</italic>
 or <italic>BRCA2.</italic>
</p>
</sec>
<sec id="S5"><title>MAIN OUTCOMES AND MEASURES</title>
<p id="P5">Breast and ovarian cancer risks.</p>
</sec>
<sec id="S6"><title>RESULTS</title>
<p id="P6">Among <italic>BRCA1</italic>
 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 <italic>BRCA2</italic>
 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 <italic>BRCA1</italic>
, 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; <italic>P</italic>
 = 2 × 10<sup>−6</sup>
), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01–1.78; <italic>P</italic>
 = .04), and c. 5261 to c.5563 (BCCR23, RHR = 1.38; 95% CI, 1.22–1.55; <italic>P</italic>
 = 6 × 10<sup>−9</sup>
). 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; <italic>P</italic>
 = 9 × 10<sup>−17</sup>
). In <italic>BRCA2</italic>
, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06–2.78; <italic>P</italic>
 = .03), c.772 to c.1806 (BCCR13; RHR = 1.63; 95% CI, 1.10–2.40; <italic>P</italic>
 = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69–3.16; <italic>P</italic>
 = .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; <italic>P</italic>
 = 6 × 10<sup>−17</sup>
). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41–0.80; <italic>P</italic>
 = .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 <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 mutation carriers.</p>
</sec>
<sec id="S7"><title>CONCLUSIONS AND RELEVANCE</title>
<p id="P7">Breast and ovarian cancer risks varied by type and location of <italic>BRCA1/2</italic>
 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 mutations.</p>
</sec>
</div>
</front>
</TEI>
<pmc article-type="research-article"><pmc-comment>The publisher of this article does not allow downloading of the full text in XML form.</pmc-comment>
  <pmc-dir>properties manuscript</pmc-dir>
  <front><journal-meta><journal-id journal-id-type="nlm-journal-id">7501160</journal-id>
<journal-id journal-id-type="pubmed-jr-id">5346</journal-id>
<journal-id journal-id-type="nlm-ta">JAMA</journal-id>
<journal-id journal-id-type="iso-abbrev">JAMA</journal-id>
<journal-title-group><journal-title>JAMA</journal-title>
</journal-title-group>
<issn pub-type="ppub">0098-7484</issn>
<issn pub-type="epub">1538-3598</issn>
</journal-meta>
<article-meta><article-id pub-id-type="pmid">25849179</article-id>
<article-id pub-id-type="pmc">4537700</article-id>
<article-id pub-id-type="doi">10.1001/jama.2014.5985</article-id>
<article-id pub-id-type="manuscript">NIHMS693111</article-id>
<article-categories><subj-group subj-group-type="heading"><subject>Article</subject>
</subj-group>
</article-categories>
<title-group><article-title>Association of Type and Location of <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 Mutations With Risk of Breast and Ovarian Cancer</article-title>
</title-group>
<contrib-group><contrib contrib-type="author"><name><surname>Rebbeck</surname>
<given-names>Timothy R.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Mitra</surname>
<given-names>Nandita</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Wan</surname>
<given-names>Fei</given-names>
</name>
<degrees>MS</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Sinilnikova</surname>
<given-names>Olga M.</given-names>
</name>
<degrees>PhD</degrees>
<xref rid="FN2" ref-type="author-notes">†</xref>
</contrib>
<contrib contrib-type="author"><name><surname>Healey</surname>
<given-names>Sue</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>McGuffog</surname>
<given-names>Lesley</given-names>
</name>
</contrib>
<contrib contrib-type="author"><name><surname>Mazoyer</surname>
<given-names>Sylvie</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Chenevix-Trench</surname>
<given-names>Georgia</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Easton</surname>
<given-names>Douglas F.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Antoniou</surname>
<given-names>Antonis C.</given-names>
</name>
<degrees>PhD</degrees>
</contrib>
<contrib contrib-type="author"><name><surname>Nathanson</surname>
<given-names>Katherine L.</given-names>
</name>
<degrees>MD</degrees>
</contrib>
<contrib contrib-type="author"><collab>the CIMBA Consortium</collab>
</contrib>
<aff id="A1">Abramson Cancer Center, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (Rebbeck, Nathanson); Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (Rebbeck, Mitra, Wan); Centre de Recherche en Cancérologie de Lyon, UMR Inserm, Centre Léon Bérard, Lyon, France (Sinilnikova, Mazoyer); Department of Genetics and Computational Biology, Queensland Institute of Medical Research, Brisbane, Australia (Healey, Chenevix-Trench); Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom (McGuffog, Easton, Antoniou); Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia (Nathanson)</aff>
</contrib-group>
<author-notes><corresp id="FN1">Corresponding Author: Timothy R. Rebbeck, PhD, Department of Biostatistics and Epidemiology, University of Pennsylvania Perelman School of Medicine, 217 Blockley Hall, 423 Guardian Dr, Philadelphia, PA 19104-6021 (<email>rebbeck@upenn.edu</email>
)</corresp>
<fn id="FN2"><label>†</label>
<p>Deceased.</p>
</fn>
</author-notes>
<pub-date pub-type="nihms-submitted"><day>14</day>
<month>7</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="ppub"><day>7</day>
<month>4</month>
<year>2015</year>
</pub-date>
<pub-date pub-type="pmc-release"><day>15</day>
<month>8</month>
<year>2015</year>
</pub-date>
<volume>313</volume>
<issue>13</issue>
<fpage>1347</fpage>
<lpage>1361</lpage>
<pmc-comment>elocation-id from pubmed: 10.1001/jama.2014.5985</pmc-comment>
      <abstract><sec id="S1"><title>IMPORTANCE</title>
<p id="P1">Limited information about the relationship between specific mutations in <italic>BRCA1</italic>
 or <italic>BRCA2</italic>
 (<italic>BRCA1/2</italic>
) and cancer risk exists.</p>
</sec>
<sec id="S2"><title>OBJECTIVE</title>
<p id="P2">To identify mutation-specific cancer risks for carriers of <italic>BRCA1/2</italic>
.</p>
</sec>
<sec id="S3"><title>DESIGN, SETTING, AND PARTICIPANTS</title>
<p id="P3">Observational study of women who were ascertained between 1937 and 2011 (median, 1999) and found to carry disease-associated <italic>BRCA1</italic>
 or <italic>BRCA2</italic>
 mutations. The international sample comprised 19 581 carriers of <italic>BRCA1</italic>
 mutations and 11 900 carriers of <italic>BRCA2</italic>
 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.</p>
</sec>
<sec id="S4"><title>EXPOSURES</title>
<p id="P4">Mutations of <italic>BRCA1</italic>
 or <italic>BRCA2.</italic>
</p>
</sec>
<sec id="S5"><title>MAIN OUTCOMES AND MEASURES</title>
<p id="P5">Breast and ovarian cancer risks.</p>
</sec>
<sec id="S6"><title>RESULTS</title>
<p id="P6">Among <italic>BRCA1</italic>
 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 <italic>BRCA2</italic>
 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 <italic>BRCA1</italic>
, 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; <italic>P</italic>
 = 2 × 10<sup>−6</sup>
), c.4328 to c.4945 (BCCR2; RHR = 1.34; 95% CI, 1.01–1.78; <italic>P</italic>
 = .04), and c. 5261 to c.5563 (BCCR23, RHR = 1.38; 95% CI, 1.22–1.55; <italic>P</italic>
 = 6 × 10<sup>−9</sup>
). 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; <italic>P</italic>
 = 9 × 10<sup>−17</sup>
). In <italic>BRCA2</italic>
, we observed multiple BCCRs spanning c.1 to c.596 (BCCR1; RHR = 1.71; 95% CI, 1.06–2.78; <italic>P</italic>
 = .03), c.772 to c.1806 (BCCR13; RHR = 1.63; 95% CI, 1.10–2.40; <italic>P</italic>
 = .01), and c.7394 to c.8904 (BCCR2; RHR = 2.31; 95% CI, 1.69–3.16; <italic>P</italic>
 = .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; <italic>P</italic>
 = 6 × 10<sup>−17</sup>
). The second OCCR spanned c.6645 to c.7471 (OCCR2; RHR = 0.57; 95% CI, 0.41–0.80; <italic>P</italic>
 = .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 <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 mutation carriers.</p>
</sec>
<sec id="S7"><title>CONCLUSIONS AND RELEVANCE</title>
<p id="P7">Breast and ovarian cancer risks varied by type and location of <italic>BRCA1/2</italic>
 mutations. With appropriate validation, these data may have implications for risk assessment and cancer prevention decision making for carriers of <italic>BRCA1</italic>
 and <italic>BRCA2</italic>
 mutations.</p>
</sec>
</abstract>
</article-meta>
</front>
</pmc>
</record>

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Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Association of Type and Location of BRCA1 and BRCA2 Mutations With Risk of Breast and Ovarian Cancer

Source :

Abstract

Links to Exploration step

Le document en format XML

Pour manipuler ce document sous Unix (Dilib)

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