Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers

On Behalf Of Gemo Study Collaborators

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants inmany candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysiswas performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

Original languageEnglish (US)
Pages (from-to)308-316
Number of pages9
JournalCancer Epidemiology Biomarkers and Prevention
Volume24
Issue number1
DOIs
StatePublished - Jan 1 2015

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Ovarian Neoplasms
Breast Neoplasms
Mutation
Penetrance
Modifier Genes
Genome-Wide Association Study
Genes

ASJC Scopus subject areas

  • Epidemiology
  • Oncology

Cite this

Candidate genetic modifiers for breast and ovarian cancer risk inBRCA1andBRCA2 mutation carriers. / On Behalf Of Gemo Study Collaborators.

In: Cancer Epidemiology Biomarkers and Prevention, Vol. 24, No. 1, 01.01.2015, p. 308-316.

Research output: Contribution to journalArticle

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abstract = "Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants inmany candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysiswas performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.",
author = "{On Behalf Of Gemo Study Collaborators} and Paolo Peterlongo and Jenny Chang-Claude and Moysich, {Kirsten B.} and Anja Rudolph and Schmutzler, {Rita K.} and Jacques Simard and Penny Soucy and Eeles, {Rosalind A.} and Easton, {Douglas F.} and Ute Hamann and Stefan Wilkening and Bowang Chen and Rookus, {Matti A.} and Schmidt, {Marjanka K.} and {Van Der Baan}, {Frederieke H.} and Spurdle, {Amanda B.} and Walker, {Logan C.} and Felicity Lose and Maia, {Ana Teresa} and Marco Montagna and Laura Matricardi and Jan Lubinski and Anna Jakubowska and Garcia, {Encarna B G{\'o}mez} and Olopade, {Olufunmilayo I.} and Nussbaum, {Robert L.} and Nathanson, {Katherine L.} and Domchek, {Susan M.} and Rebbeck, {Timothy R.} and Arun, {Banu K.} and Karlan, {Beth Y.} and Sandra Orsulic and Jenny Lester and Chung, {Wendy K.} and Alex Miron and Southey, {Melissa C.} and Goldgar, {David E.} and Buys, {Saundra S.} and Ramunas Janavicius and Dorfling, {Cecilia M.} and {Van Rensburg}, {Elizabeth J.} and Ding, {Yuan Chun} and Neuhausen, {Susan L.} and Hansen, {Thomas V O} and Gerdes, {Anne Marie} and Bent Ejlertsen and Lars J{\o}nson and Ana Osorio and Couch, {Fergus J} and Lindor, {Noralane Morey}",
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AU - On Behalf Of Gemo Study Collaborators

AU - Peterlongo, Paolo

AU - Chang-Claude, Jenny

AU - Moysich, Kirsten B.

AU - Rudolph, Anja

AU - Schmutzler, Rita K.

AU - Simard, Jacques

AU - Soucy, Penny

AU - Eeles, Rosalind A.

AU - Easton, Douglas F.

AU - Hamann, Ute

AU - Wilkening, Stefan

AU - Chen, Bowang

AU - Rookus, Matti A.

AU - Schmidt, Marjanka K.

AU - Van Der Baan, Frederieke H.

AU - Spurdle, Amanda B.

AU - Walker, Logan C.

AU - Lose, Felicity

AU - Maia, Ana Teresa

AU - Montagna, Marco

AU - Matricardi, Laura

AU - Lubinski, Jan

AU - Jakubowska, Anna

AU - Garcia, Encarna B Gómez

AU - Olopade, Olufunmilayo I.

AU - Nussbaum, Robert L.

AU - Nathanson, Katherine L.

AU - Domchek, Susan M.

AU - Rebbeck, Timothy R.

AU - Arun, Banu K.

AU - Karlan, Beth Y.

AU - Orsulic, Sandra

AU - Lester, Jenny

AU - Chung, Wendy K.

AU - Miron, Alex

AU - Southey, Melissa C.

AU - Goldgar, David E.

AU - Buys, Saundra S.

AU - Janavicius, Ramunas

AU - Dorfling, Cecilia M.

AU - Van Rensburg, Elizabeth J.

AU - Ding, Yuan Chun

AU - Neuhausen, Susan L.

AU - Hansen, Thomas V O

AU - Gerdes, Anne Marie

AU - Ejlertsen, Bent

AU - Jønson, Lars

AU - Osorio, Ana

AU - Couch, Fergus J

AU - Lindor, Noralane Morey

PY - 2015/1/1

Y1 - 2015/1/1

N2 - Background: BRCA1 and BRCA2 mutation carriers are at substantially increased risk for developing breast and ovarian cancer. The incomplete penetrance coupled with the variable age at diagnosis in carriers of the same mutation suggests the existence of genetic and nongenetic modifying factors. In this study, we evaluated the putative role of variants inmany candidate modifier genes. Methods: Genotyping data from 15,252 BRCA1 and 8,211 BRCA2 mutation carriers, for known variants (n = 3,248) located within or around 445 candidate genes, were available through the iCOGS custom-designed array. Breast and ovarian cancer association analysiswas performed within a retrospective cohort approach. Results: The observed P values of association ranged between 0.005 and 1.000. None of the variants was significantly associated with breast or ovarian cancer risk in either BRCA1 or BRCA2 mutation carriers, after multiple testing adjustments. Conclusion: There is little evidence that any of the evaluated candidate variants act as modifiers of breast and/or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. Impact: Genome-wide association studies have been more successful at identifying genetic modifiers of BRCA1/2 penetrance than candidate gene studies.

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