Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers

2.50
Hdl Handle:
http://hdl.handle.net/11287/593942
Title:
Candidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
Authors:
Peterlongo, P.; Chang-Claude, J.; Moysich, K. B.; Rudolph, A.; Schmutzler, R. K.; Simard, J.; Soucy, P.; Eeles, R. A.; Easton, D. F.; Hamann, U.; Wilkening, S.; Chen, B.; Rookus, M. A.; Schmidt, M. K.; van der Baan, F. H.; Spurdle, A. B.; Walker, L. C.; Lose, F.; Maia, A. T.; Montagna, M.; Matricardi, L.; Lubinski, J.; Jakubowska, A.; Gomez Garcia, E. B.; Olopade, O. I.; Nussbaum, R. L.; Nathanson, K. L.; Domchek, S. M.; Rebbeck, T. R.; Arun, B. K.; Karlan, B. Y.; Orsulic, S.; Lester, J.; Chung, W. K.; Miron, A.; Southey, M. C.; Goldgar, D. E.; Buys, S. S.; Janavicius, R.; Dorfling, C. M.; van Rensburg, E. J.; Ding, Y. C.; Neuhausen, S. L.; Hansen, T. V.; Gerdes, A. M.; Ejlertsen, B.; Jonson, L.; Osorio, A.; Martinez-Bouzas, C.; Benitez, J.; Conway, E. E.; Blazer, K. R.; Weitzel, J. N.; Manoukian, S.; Peissel, B.; Zaffaroni, D.; Scuvera, G.; Barile, M.; Ficarazzi, F.; Mariette, F.; Fortuzzi, S.; Viel, A.; Giannini, G.; Papi, L.; Martayan, A.; Tibiletti, M. G.; Radice, P.; Vratimos, A.; Fostira, F.; Garber, J. E.; Donaldson, A.; Brewer, Carole; Foo, C.; Evans, D. G.; Frost, D.; Eccles, D.; Brady, A.; Cook, J.; Tischkowitz, M.; Adlard, J.; Barwell, J.; Walker, L.; Izatt, L.; Side, L. E.; Kennedy, M. J.; Rogers, M. T.; Porteous, M. E.; Morrison, P. J.; Platte, R.; Davidson, R.; Hodgson, S. V.; Ellis, S.; Cole, T.; Embrace,; Godwin, A. K.; Claes, K.; Van Maerken, T.; Meindl, A.; Gehrig, A.; Sutter, C.; Engel, C.; Niederacher, D.; Steinemann, D.; Plendl, H.; Kast, K.; Rhiem, K.; Ditsch, N.; Arnold, N.; Varon-Mateeva, R.; Wappenschmidt, B.; Wang-Gohrke, S.; Bressac-de Paillerets, B.; Buecher, B.; Delnatte, C.; Houdayer, C.; Stoppa-Lyonnet, D.; Damiola, F.; Coupier, I.; Barjhoux, L.; Venat-Bouvet, L.; Golmard, L.; Boutry-Kryza, N.; Sinilnikova, O. M.; Caron, O.; Pujol, P.; Mazoyer, S.; Belotti, M.; Gemo Study Collaborators; Piedmonte, M.; Friedlander, M. L.; Rodriguez, G. C.; Copeland, L. J.; de la Hoya, M.; Segura, P. P.; Nevanlinna, H.; Aittomaki, K.; van Os, T. A.; Meijers-Heijboer, H. E.; van der Hout, A. H.; Vreeswijk, M. P.; Hoogerbrugge, N.; Ausems, M. G.; van Doorn, H. C.; Collee, J. M.; Hebon,; Olah, E.; Diez, O.; Blanco, I.; Lazaro, C.; Brunet, J.; Feliubadalo, L.; Cybulski, C.; Gronwald, J.; Durda, K.; Jaworska-Bieniek, K.; Sukiennicki, G.; Arason, A.; Chiquette, J.; Teixeira, M. R.; Olswold, C.; Couch, F. J.; Lindor, N. M.; Wang, X.; Szabo, C. I.; Offit, K.; Corines, M.; Jacobs, L.; Robson, M. E.; Zhang, L.; Joseph, V.; Berger, A.; Singer, C. F.; Rappaport, C.; Kaulich, D. G.; Pfeiler, G.; Tea, M. K.; Phelan, C. M.; Greene, M. H.; Mai, P. L.; Rennert, G.; Mulligan, A. M.; Glendon, G.; Tchatchou, S.; Andrulis, I. L.; Toland, A. E.; Bojesen, A.; Pedersen, I. S.; Thomassen, M.; Jensen, U. B.; Laitman, Y.; Rantala, J.; von Wachenfeldt, A.; Ehrencrona, H.; Askmalm, M. S.; Borg, A.; Kuchenbaecker, K. B.; McGuffog, L.; Barrowdale, D.; Healey, S.; Lee, A.; Pharoah, P. D.; Chenevix-Trench, G.; K. ConFab Investigators; Antoniou, A. C.; Friedman, E.
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 in many 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 analysis was 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.
Citation:
Cancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):308-16.
Publisher:
Cancer Epidemiol Biomarkers Prev
Journal:
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
Issue Date:
1-Jan-2015
URI:
http://hdl.handle.net/11287/593942
DOI:
10.1158/1055-9965.EPI-14-0532
PubMed ID:
25336561
Additional Links:
http://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25336561
Note:
This article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.
Type:
Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.
Language:
eng
ISSN:
1538-7755
Appears in Collections:
2015 RD&E publications; Clinical Genetics (Peninsula Genetics)

Full metadata record

DC FieldValue Language
dc.contributor.authorPeterlongo, P.en
dc.contributor.authorChang-Claude, J.en
dc.contributor.authorMoysich, K. B.en
dc.contributor.authorRudolph, A.en
dc.contributor.authorSchmutzler, R. K.en
dc.contributor.authorSimard, J.en
dc.contributor.authorSoucy, P.en
dc.contributor.authorEeles, R. A.en
dc.contributor.authorEaston, D. F.en
dc.contributor.authorHamann, U.en
dc.contributor.authorWilkening, S.en
dc.contributor.authorChen, B.en
dc.contributor.authorRookus, M. A.en
dc.contributor.authorSchmidt, M. K.en
dc.contributor.authorvan der Baan, F. H.en
dc.contributor.authorSpurdle, A. B.en
dc.contributor.authorWalker, L. C.en
dc.contributor.authorLose, F.en
dc.contributor.authorMaia, A. T.en
dc.contributor.authorMontagna, M.en
dc.contributor.authorMatricardi, L.en
dc.contributor.authorLubinski, J.en
dc.contributor.authorJakubowska, A.en
dc.contributor.authorGomez Garcia, E. B.en
dc.contributor.authorOlopade, O. I.en
dc.contributor.authorNussbaum, R. L.en
dc.contributor.authorNathanson, K. L.en
dc.contributor.authorDomchek, S. M.en
dc.contributor.authorRebbeck, T. R.en
dc.contributor.authorArun, B. K.en
dc.contributor.authorKarlan, B. Y.en
dc.contributor.authorOrsulic, S.en
dc.contributor.authorLester, J.en
dc.contributor.authorChung, W. K.en
dc.contributor.authorMiron, A.en
dc.contributor.authorSouthey, M. C.en
dc.contributor.authorGoldgar, D. E.en
dc.contributor.authorBuys, S. S.en
dc.contributor.authorJanavicius, R.en
dc.contributor.authorDorfling, C. M.en
dc.contributor.authorvan Rensburg, E. J.en
dc.contributor.authorDing, Y. C.en
dc.contributor.authorNeuhausen, S. L.en
dc.contributor.authorHansen, T. V.en
dc.contributor.authorGerdes, A. M.en
dc.contributor.authorEjlertsen, B.en
dc.contributor.authorJonson, L.en
dc.contributor.authorOsorio, A.en
dc.contributor.authorMartinez-Bouzas, C.en
dc.contributor.authorBenitez, J.en
dc.contributor.authorConway, E. E.en
dc.contributor.authorBlazer, K. R.en
dc.contributor.authorWeitzel, J. N.en
dc.contributor.authorManoukian, S.en
dc.contributor.authorPeissel, B.en
dc.contributor.authorZaffaroni, D.en
dc.contributor.authorScuvera, G.en
dc.contributor.authorBarile, M.en
dc.contributor.authorFicarazzi, F.en
dc.contributor.authorMariette, F.en
dc.contributor.authorFortuzzi, S.en
dc.contributor.authorViel, A.en
dc.contributor.authorGiannini, G.en
dc.contributor.authorPapi, L.en
dc.contributor.authorMartayan, A.en
dc.contributor.authorTibiletti, M. G.en
dc.contributor.authorRadice, P.en
dc.contributor.authorVratimos, A.en
dc.contributor.authorFostira, F.en
dc.contributor.authorGarber, J. E.en
dc.contributor.authorDonaldson, A.en
dc.contributor.authorBrewer, Caroleen
dc.contributor.authorFoo, C.en
dc.contributor.authorEvans, D. G.en
dc.contributor.authorFrost, D.en
dc.contributor.authorEccles, D.en
dc.contributor.authorBrady, A.en
dc.contributor.authorCook, J.en
dc.contributor.authorTischkowitz, M.en
dc.contributor.authorAdlard, J.en
dc.contributor.authorBarwell, J.en
dc.contributor.authorWalker, L.en
dc.contributor.authorIzatt, L.en
dc.contributor.authorSide, L. E.en
dc.contributor.authorKennedy, M. J.en
dc.contributor.authorRogers, M. T.en
dc.contributor.authorPorteous, M. E.en
dc.contributor.authorMorrison, P. J.en
dc.contributor.authorPlatte, R.en
dc.contributor.authorDavidson, R.en
dc.contributor.authorHodgson, S. V.en
dc.contributor.authorEllis, S.en
dc.contributor.authorCole, T.en
dc.contributor.authorEmbrace,en
dc.contributor.authorGodwin, A. K.en
dc.contributor.authorClaes, K.en
dc.contributor.authorVan Maerken, T.en
dc.contributor.authorMeindl, A.en
dc.contributor.authorGehrig, A.en
dc.contributor.authorSutter, C.en
dc.contributor.authorEngel, C.en
dc.contributor.authorNiederacher, D.en
dc.contributor.authorSteinemann, D.en
dc.contributor.authorPlendl, H.en
dc.contributor.authorKast, K.en
dc.contributor.authorRhiem, K.en
dc.contributor.authorDitsch, N.en
dc.contributor.authorArnold, N.en
dc.contributor.authorVaron-Mateeva, R.en
dc.contributor.authorWappenschmidt, B.en
dc.contributor.authorWang-Gohrke, S.en
dc.contributor.authorBressac-de Paillerets, B.en
dc.contributor.authorBuecher, B.en
dc.contributor.authorDelnatte, C.en
dc.contributor.authorHoudayer, C.en
dc.contributor.authorStoppa-Lyonnet, D.en
dc.contributor.authorDamiola, F.en
dc.contributor.authorCoupier, I.en
dc.contributor.authorBarjhoux, L.en
dc.contributor.authorVenat-Bouvet, L.en
dc.contributor.authorGolmard, L.en
dc.contributor.authorBoutry-Kryza, N.en
dc.contributor.authorSinilnikova, O. M.en
dc.contributor.authorCaron, O.en
dc.contributor.authorPujol, P.en
dc.contributor.authorMazoyer, S.en
dc.contributor.authorBelotti, M.en
dc.contributor.authorGemo Study Collaboratorsen
dc.contributor.authorPiedmonte, M.en
dc.contributor.authorFriedlander, M. L.en
dc.contributor.authorRodriguez, G. C.en
dc.contributor.authorCopeland, L. J.en
dc.contributor.authorde la Hoya, M.en
dc.contributor.authorSegura, P. P.en
dc.contributor.authorNevanlinna, H.en
dc.contributor.authorAittomaki, K.en
dc.contributor.authorvan Os, T. A.en
dc.contributor.authorMeijers-Heijboer, H. E.en
dc.contributor.authorvan der Hout, A. H.en
dc.contributor.authorVreeswijk, M. P.en
dc.contributor.authorHoogerbrugge, N.en
dc.contributor.authorAusems, M. G.en
dc.contributor.authorvan Doorn, H. C.en
dc.contributor.authorCollee, J. M.en
dc.contributor.authorHebon,en
dc.contributor.authorOlah, E.en
dc.contributor.authorDiez, O.en
dc.contributor.authorBlanco, I.en
dc.contributor.authorLazaro, C.en
dc.contributor.authorBrunet, J.en
dc.contributor.authorFeliubadalo, L.en
dc.contributor.authorCybulski, C.en
dc.contributor.authorGronwald, J.en
dc.contributor.authorDurda, K.en
dc.contributor.authorJaworska-Bieniek, K.en
dc.contributor.authorSukiennicki, G.en
dc.contributor.authorArason, A.en
dc.contributor.authorChiquette, J.en
dc.contributor.authorTeixeira, M. R.en
dc.contributor.authorOlswold, C.en
dc.contributor.authorCouch, F. J.en
dc.contributor.authorLindor, N. M.en
dc.contributor.authorWang, X.en
dc.contributor.authorSzabo, C. I.en
dc.contributor.authorOffit, K.en
dc.contributor.authorCorines, M.en
dc.contributor.authorJacobs, L.en
dc.contributor.authorRobson, M. E.en
dc.contributor.authorZhang, L.en
dc.contributor.authorJoseph, V.en
dc.contributor.authorBerger, A.en
dc.contributor.authorSinger, C. F.en
dc.contributor.authorRappaport, C.en
dc.contributor.authorKaulich, D. G.en
dc.contributor.authorPfeiler, G.en
dc.contributor.authorTea, M. K.en
dc.contributor.authorPhelan, C. M.en
dc.contributor.authorGreene, M. H.en
dc.contributor.authorMai, P. L.en
dc.contributor.authorRennert, G.en
dc.contributor.authorMulligan, A. M.en
dc.contributor.authorGlendon, G.en
dc.contributor.authorTchatchou, S.en
dc.contributor.authorAndrulis, I. L.en
dc.contributor.authorToland, A. E.en
dc.contributor.authorBojesen, A.en
dc.contributor.authorPedersen, I. S.en
dc.contributor.authorThomassen, M.en
dc.contributor.authorJensen, U. B.en
dc.contributor.authorLaitman, Y.en
dc.contributor.authorRantala, J.en
dc.contributor.authorvon Wachenfeldt, A.en
dc.contributor.authorEhrencrona, H.en
dc.contributor.authorAskmalm, M. S.en
dc.contributor.authorBorg, A.en
dc.contributor.authorKuchenbaecker, K. B.en
dc.contributor.authorMcGuffog, L.en
dc.contributor.authorBarrowdale, D.en
dc.contributor.authorHealey, S.en
dc.contributor.authorLee, A.en
dc.contributor.authorPharoah, P. D.en
dc.contributor.authorChenevix-Trench, G.en
dc.contributor.authorK. ConFab Investigatorsen
dc.contributor.authorAntoniou, A. C.en
dc.contributor.authorFriedman, E.en
dc.date.accessioned2016-01-19T12:37:43Zen
dc.date.available2016-01-19T12:37:43Zen
dc.date.issued2015-01-01en
dc.identifier.citationCancer Epidemiol Biomarkers Prev. 2015 Jan;24(1):308-16.en
dc.identifier.issn1538-7755en
dc.identifier.pmid25336561en
dc.identifier.doi10.1158/1055-9965.EPI-14-0532en
dc.identifier.urihttp://hdl.handle.net/11287/593942en
dc.description.abstractBACKGROUND: 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 in many 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 analysis was 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.en
dc.language.isoengen
dc.publisherCancer Epidemiol Biomarkers Preven
dc.relation.urlhttp://cebp.aacrjournals.org/cgi/pmidlookup?view=long&pmid=25336561en
dc.titleCandidate genetic modifiers for breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriersen
dc.typeJournal Articleen
dc.typeResearch Support, N.I.H., Extramuralen
dc.typeResearch Support, Non-U.S. Gov'ten
dc.typeResearch Support, U.S. Gov't, Non-P.H.S.en
dc.identifier.journalCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncologyen
dc.description.noteThis article is available via Open Access. Please click on the 'Additional Link' above to access the full-text.en

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