Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europea...
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Public Library of Science (PLoS)
2012
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Acceso en línea: | https://doaj.org/article/bcfd88daf90c42a397f31d12f9e2759f |
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Medicine R Science Q Rebecca Hein Melanie Maranian John L Hopper Miroslaw K Kapuscinski Melissa C Southey Daniel J Park Marjanka K Schmidt Annegien Broeks Frans B L Hogervorst H Bas Bueno-de-Mesquita Kenneth R Muir Artitaya Lophatananon Suthee Rattanamongkongul Puttisak Puttawibul Peter A Fasching Alexander Hein Arif B Ekici Matthias W Beckmann Olivia Fletcher Nichola Johnson Isabel dos Santos Silva Julian Peto Elinor Sawyer Ian Tomlinson Michael Kerin Nicola Miller Frederick Marmee Andreas Schneeweiss Christof Sohn Barbara Burwinkel Pascal Guénel Emilie Cordina-Duverger Florence Menegaux Thérèse Truong Stig E Bojesen Børge G Nordestgaard Henrik Flyger Roger L Milne Jose Ignacio Arias Perez M Pilar Zamora Javier Benítez Hoda Anton-Culver Argyrios Ziogas Leslie Bernstein Christina A Clarke Hermann Brenner Heiko Müller Volker Arndt Christa Stegmaier Nazneen Rahman Sheila Seal Clare Turnbull Anthony Renwick Alfons Meindl Sarah Schott Claus R Bartram Rita K Schmutzler Hiltrud Brauch Ute Hamann Yon-Dschun Ko GENICA Network Shan Wang-Gohrke Thilo Dörk Peter Schürmann Johann H Karstens Peter Hillemanns Heli Nevanlinna Tuomas Heikkinen Kristiina Aittomäki Carl Blomqvist Natalia V Bogdanova Iosif V Zalutsky Natalia N Antonenkova Marina Bermisheva Darya Prokovieva Albina Farahtdinova Elza Khusnutdinova Annika Lindblom Sara Margolin Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana Hartikainen Xiaoqing Chen Jonathan Beesley Kconfab Investigators AOCS Group Diether Lambrechts Hui Zhao Patrick Neven Hans Wildiers Stefan Nickels Dieter Flesch-Janys Paolo Radice Paolo Peterlongo Siranoush Manoukian Monica Barile Fergus J Couch Janet E Olson Xianshu Wang Zachary Fredericksen Graham G Giles Laura Baglietto Catriona A McLean Gianluca Severi Kenneth Offit Mark Robson Mia M Gaudet Joseph Vijai Grethe Grenaker Alnæs Vessela Kristensen Anne-Lise Børresen-Dale Esther M John Alexander Miron Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Mervi Grip Irene L Andrulis Julia A Knight Gord Glendon Anna Marie Mulligan Jonine D Figueroa Montserrat García-Closas Jolanta Lissowska Mark E Sherman Maartje Hooning John W M Martens Caroline Seynaeve Margriet Collée Per Hall Keith Humpreys Kamila Czene Jianjun Liu Angela Cox Ian W Brock Simon S Cross Malcolm W R Reed Shahana Ahmed Maya Ghoussaini Paul D P Pharoah Daehee Kang Keun-Young Yoo Dong-Young Noh Anna Jakubowska Katarzyna Jaworska Katarzyna Durda Elżbieta Złowocka Suleeporn Sangrajrang Valerie Gaborieau Paul Brennan James McKay Chen-Yang Shen Jyh-Cherng Yu Huan-Ming Hsu Ming-Feng Hou Nick Orr Minouk Schoemaker Alan Ashworth Anthony Swerdlow Amy Trentham-Dietz Polly A Newcomb Linda Titus Kathleen M Egan Georgia Chenevix-Trench Antonis C Antoniou Manjeet K Humphreys Jonathan Morrison Jenny Chang-Claude Douglas F Easton Alison M Dunning Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
description |
The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours. |
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Rebecca Hein Melanie Maranian John L Hopper Miroslaw K Kapuscinski Melissa C Southey Daniel J Park Marjanka K Schmidt Annegien Broeks Frans B L Hogervorst H Bas Bueno-de-Mesquita Kenneth R Muir Artitaya Lophatananon Suthee Rattanamongkongul Puttisak Puttawibul Peter A Fasching Alexander Hein Arif B Ekici Matthias W Beckmann Olivia Fletcher Nichola Johnson Isabel dos Santos Silva Julian Peto Elinor Sawyer Ian Tomlinson Michael Kerin Nicola Miller Frederick Marmee Andreas Schneeweiss Christof Sohn Barbara Burwinkel Pascal Guénel Emilie Cordina-Duverger Florence Menegaux Thérèse Truong Stig E Bojesen Børge G Nordestgaard Henrik Flyger Roger L Milne Jose Ignacio Arias Perez M Pilar Zamora Javier Benítez Hoda Anton-Culver Argyrios Ziogas Leslie Bernstein Christina A Clarke Hermann Brenner Heiko Müller Volker Arndt Christa Stegmaier Nazneen Rahman Sheila Seal Clare Turnbull Anthony Renwick Alfons Meindl Sarah Schott Claus R Bartram Rita K Schmutzler Hiltrud Brauch Ute Hamann Yon-Dschun Ko GENICA Network Shan Wang-Gohrke Thilo Dörk Peter Schürmann Johann H Karstens Peter Hillemanns Heli Nevanlinna Tuomas Heikkinen Kristiina Aittomäki Carl Blomqvist Natalia V Bogdanova Iosif V Zalutsky Natalia N Antonenkova Marina Bermisheva Darya Prokovieva Albina Farahtdinova Elza Khusnutdinova Annika Lindblom Sara Margolin Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana Hartikainen Xiaoqing Chen Jonathan Beesley Kconfab Investigators AOCS Group Diether Lambrechts Hui Zhao Patrick Neven Hans Wildiers Stefan Nickels Dieter Flesch-Janys Paolo Radice Paolo Peterlongo Siranoush Manoukian Monica Barile Fergus J Couch Janet E Olson Xianshu Wang Zachary Fredericksen Graham G Giles Laura Baglietto Catriona A McLean Gianluca Severi Kenneth Offit Mark Robson Mia M Gaudet Joseph Vijai Grethe Grenaker Alnæs Vessela Kristensen Anne-Lise Børresen-Dale Esther M John Alexander Miron Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Mervi Grip Irene L Andrulis Julia A Knight Gord Glendon Anna Marie Mulligan Jonine D Figueroa Montserrat García-Closas Jolanta Lissowska Mark E Sherman Maartje Hooning John W M Martens Caroline Seynaeve Margriet Collée Per Hall Keith Humpreys Kamila Czene Jianjun Liu Angela Cox Ian W Brock Simon S Cross Malcolm W R Reed Shahana Ahmed Maya Ghoussaini Paul D P Pharoah Daehee Kang Keun-Young Yoo Dong-Young Noh Anna Jakubowska Katarzyna Jaworska Katarzyna Durda Elżbieta Złowocka Suleeporn Sangrajrang Valerie Gaborieau Paul Brennan James McKay Chen-Yang Shen Jyh-Cherng Yu Huan-Ming Hsu Ming-Feng Hou Nick Orr Minouk Schoemaker Alan Ashworth Anthony Swerdlow Amy Trentham-Dietz Polly A Newcomb Linda Titus Kathleen M Egan Georgia Chenevix-Trench Antonis C Antoniou Manjeet K Humphreys Jonathan Morrison Jenny Chang-Claude Douglas F Easton Alison M Dunning |
author_facet |
Rebecca Hein Melanie Maranian John L Hopper Miroslaw K Kapuscinski Melissa C Southey Daniel J Park Marjanka K Schmidt Annegien Broeks Frans B L Hogervorst H Bas Bueno-de-Mesquita Kenneth R Muir Artitaya Lophatananon Suthee Rattanamongkongul Puttisak Puttawibul Peter A Fasching Alexander Hein Arif B Ekici Matthias W Beckmann Olivia Fletcher Nichola Johnson Isabel dos Santos Silva Julian Peto Elinor Sawyer Ian Tomlinson Michael Kerin Nicola Miller Frederick Marmee Andreas Schneeweiss Christof Sohn Barbara Burwinkel Pascal Guénel Emilie Cordina-Duverger Florence Menegaux Thérèse Truong Stig E Bojesen Børge G Nordestgaard Henrik Flyger Roger L Milne Jose Ignacio Arias Perez M Pilar Zamora Javier Benítez Hoda Anton-Culver Argyrios Ziogas Leslie Bernstein Christina A Clarke Hermann Brenner Heiko Müller Volker Arndt Christa Stegmaier Nazneen Rahman Sheila Seal Clare Turnbull Anthony Renwick Alfons Meindl Sarah Schott Claus R Bartram Rita K Schmutzler Hiltrud Brauch Ute Hamann Yon-Dschun Ko GENICA Network Shan Wang-Gohrke Thilo Dörk Peter Schürmann Johann H Karstens Peter Hillemanns Heli Nevanlinna Tuomas Heikkinen Kristiina Aittomäki Carl Blomqvist Natalia V Bogdanova Iosif V Zalutsky Natalia N Antonenkova Marina Bermisheva Darya Prokovieva Albina Farahtdinova Elza Khusnutdinova Annika Lindblom Sara Margolin Arto Mannermaa Vesa Kataja Veli-Matti Kosma Jaana Hartikainen Xiaoqing Chen Jonathan Beesley Kconfab Investigators AOCS Group Diether Lambrechts Hui Zhao Patrick Neven Hans Wildiers Stefan Nickels Dieter Flesch-Janys Paolo Radice Paolo Peterlongo Siranoush Manoukian Monica Barile Fergus J Couch Janet E Olson Xianshu Wang Zachary Fredericksen Graham G Giles Laura Baglietto Catriona A McLean Gianluca Severi Kenneth Offit Mark Robson Mia M Gaudet Joseph Vijai Grethe Grenaker Alnæs Vessela Kristensen Anne-Lise Børresen-Dale Esther M John Alexander Miron Robert Winqvist Katri Pylkäs Arja Jukkola-Vuorinen Mervi Grip Irene L Andrulis Julia A Knight Gord Glendon Anna Marie Mulligan Jonine D Figueroa Montserrat García-Closas Jolanta Lissowska Mark E Sherman Maartje Hooning John W M Martens Caroline Seynaeve Margriet Collée Per Hall Keith Humpreys Kamila Czene Jianjun Liu Angela Cox Ian W Brock Simon S Cross Malcolm W R Reed Shahana Ahmed Maya Ghoussaini Paul D P Pharoah Daehee Kang Keun-Young Yoo Dong-Young Noh Anna Jakubowska Katarzyna Jaworska Katarzyna Durda Elżbieta Złowocka Suleeporn Sangrajrang Valerie Gaborieau Paul Brennan James McKay Chen-Yang Shen Jyh-Cherng Yu Huan-Ming Hsu Ming-Feng Hou Nick Orr Minouk Schoemaker Alan Ashworth Anthony Swerdlow Amy Trentham-Dietz Polly A Newcomb Linda Titus Kathleen M Egan Georgia Chenevix-Trench Antonis C Antoniou Manjeet K Humphreys Jonathan Morrison Jenny Chang-Claude Douglas F Easton Alison M Dunning |
author_sort |
Rebecca Hein |
title |
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
title_short |
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
title_full |
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
title_fullStr |
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
title_full_unstemmed |
Comparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC). |
title_sort |
comparison of 6q25 breast cancer hits from asian and european genome wide association studies in the breast cancer association consortium (bcac). |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/bcfd88daf90c42a397f31d12f9e2759f |
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oai:doaj.org-article:bcfd88daf90c42a397f31d12f9e2759f2021-11-18T07:09:30ZComparison of 6q25 breast cancer hits from Asian and European Genome Wide Association Studies in the Breast Cancer Association Consortium (BCAC).1932-620310.1371/journal.pone.0042380https://doaj.org/article/bcfd88daf90c42a397f31d12f9e2759f2012-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0042380https://doaj.org/toc/1932-6203The 6q25.1 locus was first identified via a genome-wide association study (GWAS) in Chinese women and marked by single nucleotide polymorphism (SNP) rs2046210, approximately 180 Kb upstream of ESR1. There have been conflicting reports about the association of this locus with breast cancer in Europeans, and a GWAS in Europeans identified a different SNP, tagged here by rs12662670. We examined the associations of both SNPs in up to 61,689 cases and 58,822 controls from forty-four studies collaborating in the Breast Cancer Association Consortium, of which four studies were of Asian and 39 of European descent. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI). Case-only analyses were used to compare SNP effects in Estrogen Receptor positive (ER+) versus negative (ER-) tumours. Models including both SNPs were fitted to investigate whether the SNP effects were independent. Both SNPs are significantly associated with breast cancer risk in both ethnic groups. Per-allele ORs are higher in Asian than in European studies [rs2046210: OR (A/G) = 1.36 (95% CI 1.26-1.48), p = 7.6 × 10(-14) in Asians and 1.09 (95% CI 1.07-1.11), p = 6.8 × 10(-18) in Europeans. rs12662670: OR (G/T) = 1.29 (95% CI 1.19-1.41), p = 1.2 × 10(-9) in Asians and 1.12 (95% CI 1.08-1.17), p = 3.8 × 10(-9) in Europeans]. SNP rs2046210 is associated with a significantly greater risk of ER- than ER+ tumours in Europeans [OR (ER-) = 1.20 (95% CI 1.15-1.25), p = 1.8 × 10(-17) versus OR (ER+) = 1.07 (95% CI 1.04-1.1), p = 1.3 × 10(-7), p(heterogeneity) = 5.1 × 10(-6)]. In these Asian studies, by contrast, there is no clear evidence of a differential association by tumour receptor status. Each SNP is associated with risk after adjustment for the other SNP. These results suggest the presence of two variants at 6q25.1 each independently associated with breast cancer risk in Asians and in Europeans. Of these two, the one tagged by rs2046210 is associated with a greater risk of ER- tumours.Rebecca HeinMelanie MaranianJohn L HopperMiroslaw K KapuscinskiMelissa C SoutheyDaniel J ParkMarjanka K SchmidtAnnegien BroeksFrans B L HogervorstH Bas Bueno-de-MesquitaKenneth R MuirArtitaya LophatananonSuthee RattanamongkongulPuttisak PuttawibulPeter A FaschingAlexander HeinArif B EkiciMatthias W BeckmannOlivia FletcherNichola JohnsonIsabel dos Santos SilvaJulian PetoElinor SawyerIan TomlinsonMichael KerinNicola MillerFrederick MarmeeAndreas SchneeweissChristof SohnBarbara BurwinkelPascal GuénelEmilie Cordina-DuvergerFlorence MenegauxThérèse TruongStig E BojesenBørge G NordestgaardHenrik FlygerRoger L MilneJose Ignacio Arias PerezM Pilar ZamoraJavier BenítezHoda Anton-CulverArgyrios ZiogasLeslie BernsteinChristina A ClarkeHermann BrennerHeiko MüllerVolker ArndtChrista StegmaierNazneen RahmanSheila SealClare TurnbullAnthony RenwickAlfons MeindlSarah SchottClaus R BartramRita K SchmutzlerHiltrud BrauchUte HamannYon-Dschun KoGENICA NetworkShan Wang-GohrkeThilo DörkPeter SchürmannJohann H KarstensPeter HillemannsHeli NevanlinnaTuomas HeikkinenKristiina AittomäkiCarl BlomqvistNatalia V BogdanovaIosif V ZalutskyNatalia N AntonenkovaMarina BermishevaDarya ProkovievaAlbina FarahtdinovaElza KhusnutdinovaAnnika LindblomSara MargolinArto MannermaaVesa KatajaVeli-Matti KosmaJaana HartikainenXiaoqing ChenJonathan BeesleyKconfab InvestigatorsAOCS GroupDiether LambrechtsHui ZhaoPatrick NevenHans WildiersStefan NickelsDieter Flesch-JanysPaolo RadicePaolo PeterlongoSiranoush ManoukianMonica BarileFergus J CouchJanet E OlsonXianshu WangZachary FredericksenGraham G GilesLaura BagliettoCatriona A McLeanGianluca SeveriKenneth OffitMark RobsonMia M GaudetJoseph VijaiGrethe Grenaker AlnæsVessela KristensenAnne-Lise Børresen-DaleEsther M JohnAlexander MironRobert WinqvistKatri PylkäsArja Jukkola-VuorinenMervi GripIrene L AndrulisJulia A KnightGord GlendonAnna Marie MulliganJonine D FigueroaMontserrat García-ClosasJolanta LissowskaMark E ShermanMaartje HooningJohn W M MartensCaroline SeynaeveMargriet ColléePer HallKeith HumpreysKamila CzeneJianjun LiuAngela CoxIan W BrockSimon S CrossMalcolm W R ReedShahana AhmedMaya GhoussainiPaul D P PharoahDaehee KangKeun-Young YooDong-Young NohAnna JakubowskaKatarzyna JaworskaKatarzyna DurdaElżbieta ZłowockaSuleeporn SangrajrangValerie GaborieauPaul BrennanJames McKayChen-Yang ShenJyh-Cherng YuHuan-Ming HsuMing-Feng HouNick OrrMinouk SchoemakerAlan AshworthAnthony SwerdlowAmy Trentham-DietzPolly A NewcombLinda TitusKathleen M EganGeorgia Chenevix-TrenchAntonis C AntoniouManjeet K HumphreysJonathan MorrisonJenny Chang-ClaudeDouglas F EastonAlison M DunningPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 8, p e42380 (2012) |