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dc.contributor.authorGarcia-Closas, Montserrat
dc.contributor.authorHall, Per
dc.contributor.authorNevanlinna, Heli
dc.contributor.authorPooley, Karen
dc.contributor.authorMorrison, Jonathan
dc.contributor.authorRichesson, Douglas A.
dc.contributor.authorBojesen, Stig E.
dc.contributor.authorNordestgaard, Børge G.
dc.contributor.authorAxelsson, Christen K.
dc.contributor.authorArias, Jose I.
dc.contributor.authorMilne, Roger L.
dc.contributor.authorRibas, Gloria
dc.contributor.authorGonzález-Neira, Anna
dc.contributor.authorBenítez, Javier
dc.contributor.authorZamora, Pilar
dc.contributor.authorBrauch, Hiltrud
dc.contributor.authorJustenhoven, Christina
dc.contributor.authorHamann, Ute
dc.contributor.authorKo, Yon-Dschun
dc.contributor.authorBruening, Thomas
dc.contributor.authorHaas, Susanne
dc.contributor.authorDörk, Thilo
dc.contributor.authorSchürmann, Peter
dc.contributor.authorHillemanns, Peter
dc.contributor.authorBogdanova, Natalia
dc.contributor.authorBremer, Michael
dc.contributor.authorKarstens, Johann Hinrich
dc.contributor.authorFagerholm, Rainer
dc.contributor.authorAaltonen, Kirsimari
dc.contributor.authorAittomäki, Kristiina
dc.contributor.authorvon Smitten, Karl
dc.contributor.authorBlomqvist, Carl
dc.contributor.authorMannermaa, Arto
dc.contributor.authorUusitupa, Matti
dc.contributor.authorEskelinen, Matti
dc.contributor.authorTengström, Maria
dc.contributor.authorKosma, Veli-Matti
dc.contributor.authorKataja, Vesa
dc.contributor.authorChenevix-Trench, Georgia
dc.contributor.authorSpurdle, Amanda B.
dc.contributor.authorBeesley, Jonathan
dc.contributor.authorChen, Xiaoqing
dc.contributor.authorAustralian Ovarian Cancer Management Group
dc.contributor.authorKathleen Cuningham Foundation Consortium for Research into Familial Breast Cancer
dc.contributor.authorDevilee, Peter
dc.contributor.authorvan Asperen, Christi J.
dc.contributor.authorJacobi, Catharina E.
dc.contributor.authorTollenaar, Rob A. E. M.
dc.contributor.authorHuijts, Petra E. A.
dc.contributor.authorKlijn, Jan G. M.
dc.contributor.authorChang-Claude, Jenny
dc.contributor.authorKropp, Silke
dc.contributor.authorSlanger, Tracy
dc.contributor.authorFlesch-Janys, Dieter
dc.contributor.authorMutschelknauss, Elke
dc.contributor.authorSalazar, Ramona
dc.contributor.authorWang-Gohrke, Shan
dc.contributor.authorCouch, Fergus
dc.contributor.authorGoode, Ellen L.
dc.contributor.authorOlson, Janet E.
dc.contributor.authorVachon, Celine
dc.contributor.authorFredericksen, Zachary S.
dc.contributor.authorGiles, Graham G.
dc.contributor.authorBaglietto, Laura
dc.contributor.authorSeveri, Gianluca
dc.contributor.authorHopper, John L.
dc.contributor.authorEnglish, Dallas R.
dc.contributor.authorSouthey, Melissa C.
dc.contributor.authorHaiman, Christopher A.
dc.contributor.authorHenderson, Brian E.
dc.contributor.authorKolonel, Laurence N.
dc.contributor.authorLe Marchand, Loic
dc.contributor.authorStram, Daniel O.
dc.contributor.authorHunter, David J.
dc.contributor.authorHankinson, Susan E.
dc.contributor.authorCox, David G.
dc.contributor.authorTamimi, Rulla
dc.contributor.authorKraft, Peter
dc.contributor.authorSherman, Mark E.
dc.contributor.authorChanock, Stephen J.
dc.contributor.authorLissowska, Jolanta
dc.contributor.authorBrinton, Louise A.
dc.contributor.authorPeplonska, Beata
dc.contributor.authorKlijn, Jan G. M.
dc.contributor.authorHooning, Maartje J.
dc.contributor.authorMeijers-Heijboer, Han
dc.contributor.authorCollee, J. Margriet
dc.contributor.authorvan den Ouweland, Ans
dc.contributor.authorUitterlinden, Andre G.
dc.contributor.authorLiu, Jianjun
dc.contributor.authorLin, Low Yen
dc.contributor.authorYuqing, Li
dc.contributor.authorHumphreys, Keith
dc.contributor.authorCzene, Kamila
dc.contributor.authorCox, Angela
dc.contributor.authorBalasubramanian, Sabapathy P.
dc.contributor.authorCross, Simon S.
dc.contributor.authorReed, Malcolm W. R.
dc.contributor.authorBlows, Fiona
dc.contributor.authorDriver, Kristy
dc.date.accessioned2019-09-30T11:55:49Z
dc.date.issued2008
dc.identifier.citationGarcia-Closas, Montserrat, Per Hall, Heli Nevanlinna, Karen Pooley, Jonathan Morrison, Douglas A. Richesson, Stig E. Bojesen, et al. 2008. “Heterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics.” Edited by Suzanne M. Leal. PLoS Genetics 4 (4): e1000054. https://doi.org/10.1371/journal.pgen.1000054.
dc.identifier.issn1553-7390
dc.identifier.issn1553-7404
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41426764*
dc.description.abstractA three-stage genome-wide association study recently identified single nucleotide polymorphisms ( SNPs) in five loci ( fibroblast growth receptor 2 ( FGFR2), trinucleotide repeat containing 9 ( TNRC9), mitogen-activated protein kinase 3 K1 (MAP3K1), 8q24, and lymphocyte- specific protein 1 ( LSP1)) associated with breast cancer risk. We investigated whether the associations between these SNPs and breast cancer risk varied by clinically important tumor characteristics in up to 23,039 invasive breast cancer cases and 26,273 controls from 20 studies. We also evaluated their influence on overall survival in 13,527 cases from 13 studies. All participants were of European or Asian origin. rs2981582 in FGFR2 was more strongly related to ER- positive ( per- allele OR ( 95%CI) = 1.31 (1.27-1.36)) than ER- negative (1.08 (1.03- 1.14)) disease ( P for heterogeneity = 10-(13)). This SNP was also more strongly related to PR-positive, low grade and node positive tumors (P = 10(-5), 10(-8), 0.013, respectively). The association for rs13281615 in 8q24 was stronger for ER- positive, PR-positive, and low grade tumors (P = 0.001, 0.011 and 10(-4), respectively). The differences in the associations between SNPs in FGFR2 and 8q24 and risk by ER and grade remained significant after permutation adjustment for multiple comparisons and after adjustment for other tumor characteristics. Three SNPs ( rs2981582, rs3803662, and rs889312) showed weak but significant associations with ER- negative disease, the strongest association being for rs3803662 in TNRC9 ( 1.14 ( 1.09-1.21)). rs13281615 in 8q24 was associated with an improvement in survival after diagnosis ( per- allele HR = 0.90 (0.83-0.97). The association was attenuated and non-significant after adjusting for known prognostic factors. Our findings show that common genetic variants influence the pathological subtype of breast cancer and provide further support for the hypothesis that ER- positive and ER- negative disease are biologically distinct. Understanding the etiologic heterogeneity of breast cancer may ultimately result in improvements in prevention, early detection, and treatment.
dc.language.isoen_US
dc.publisherPublic Library of Science
dash.licenseLAA
dc.titleHeterogeneity of Breast Cancer Associations with Five Susceptibility Loci by Clinical and Pathological Characteristics
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalPLoS Genetics
dash.depositing.authorTamimi, Rulla M.::40059f92d8e6f608a1ef14102dc6ecac::600
dc.date.available2019-09-30T11:55:49Z
dash.workflow.comments1Science Serial ID 83874
dc.identifier.doi10.1371/journal.pgen.1000054
dash.source.volume4;4


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