Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Kate Lawrenson; Siddhartha Kar; Karen McCue; Karoline Kuchenbaeker; Kyriaki Michailidou; Jonathan Tyrer; Jonathan Beesley; Susan J Ramus; Qiyuan Li; Melissa K Delgado; Janet M Lee; Kristiina Aittomäki; Irene L Andrulis; Hoda Anton-Culver; Volker Arndt; Banu K Arun; Brita Arver; Elisa V Bandera; Monica Barile; Rosa B Barkardottir; Daniel Barrowdale; Matthias W Beckmann; Javier Benitez; Andrew Berchuck; Maria Bisogna; Line Bjorge; Carl Blomqvist; William Blot; Natalia Bogdanova; Anders Bojesen; Stig E Bojesen; Manjeet K Bolla; Bernardo Bonanni; Anne Lise Børresen-Dale; Hiltrud Brauch; Paul Brennan; Hermann Brenner; Fiona Bruinsma; Joan Brunet; Shaik Ahmad Buhari; Barbara Burwinkel; Ralf Butzow; Saundra S Buys; Qiuyin Cai; Trinidad Caldes; Ian Campbell; Rikki Canniotto; Jenny Chang-Claude; Jocelyne Chiquette; Ji Yeob Choi; Kathleen B M Claes; Linda S Cook; Angela Cox; Daniel W Cramer; Simon S Cross; Cezary Cybulski; Kamila Czene; Mary B Daly; Francesca Damiola; Agnieszka Dansonka-Mieszkowska; Hatef Darabi; Joe Dennis; Peter Devilee; Orland Diez; Jennifer A Doherty; Susan M Domchek; Cecilia M Dorfling; Thilo Dörk; Martine Dumont; Hans Ehrencrona; Bent Ejlertsen; Steve Ellis; Christoph Engel; Eunjung Lee; D. Gareth Evans; Peter A Fasching; Lidia Feliubadalo; Jonine Figueroa; Dieter Flesch-Janys; Olivia Fletcher; Henrik Flyger; Lenka Foretova; Florentia Fostira; William D Foulkes; Brooke L Fridley; Eitan Friedman; Debra Frost; Gaetana Gambino; Patricia A Ganz; Judy Garber; Montserrat García-Closas; Aleksandra Gentry-Maharaj; Maya Ghoussaini; Graham G Giles; Rosalind Glasspool; Andrew K Godwin; Mark S Goldberg; David E Goldgar; Anna González-Neira; Ellen L Goode; Marc T Goodman; Mark H Greene; Jacek Gronwald; Pascal Guénel; Christopher A Haiman; Per Hall; Emily Hallberg; Ute Hamann; Thomas V O Hansen; Patricia A Harrington; Mikael Hartman; Norhashimah Hassan; Sue Healey; Florian Heitz; Josef Herzog; Estrid Høgdall; Claus K Høgdall; Frans B L Hogervorst; Antoinette Hollestelle; John L Hopper; Peter J Hulick; Tomasz Huzarski; Evgeny N Imyanitov; Claudine Isaacs; Hidemi Ito; Anna Jakubowska; Ramunas Janavicius; Allan Jensen; Esther M John; Nichola Johnson; Maria Kabisch; Daehee Kang; Miroslav Kapuscinski; Beth Y Karlan; Sofia Khan; Lambertus A Kiemeney; Susanne Kruger Kjaer; Julia A Knight; Irene Konstantopoulou; Veli Matti Kosma; Vessela Kristensen; Jolanta Kupryjanczyk; Ava Kwong; Miguel De La Hoya; Yael Laitman; Diether Lambrechts; Nhu Le; Kim De Leeneer; Jenny Lester; Douglas A Levine; Jingmei Li; Annika Lindblom; Jirong Long; Artitaya Lophatananon; Jennifer T Loud; Karen Lu; Jan Lubinski; Arto Mannermaa; Siranoush Manoukian; Loic Le Marchand; Sara Margolin; Frederik Marme; Leon F A G Massuger; Keitaro Matsuo; Sylvie Mazoyer; Lesley McGuffog; Catriona McLean; Iain McNeish; Alfons Meindl; Usha Menon; Arjen R Mensenkamp; Roger L Milne; Marco Montagna; Kirsten B Moysich; Kenneth Muir; Anna Marie Mulligan; Katherine L Nathanson; Roberta B Ness; Susan L Neuhausen; Heli Nevanlinna; Silje Nord; Robert L Nussbaum; Kunle Odunsi; Kenneth Offit; Edith Olah; Olufunmilayo I Olopade; Janet E Olson; Curtis Olswold; David O'Malley; Irene Orlow; Nick Orr; Ana Osorio; Sue Kyung Park; Celeste L Pearce; Tanja Pejovic; Paolo Peterlongo; Georg Pfeiler; Catherine M Phelan; Elizabeth M Poole; Katri Pylkäs; Paolo Radice; Johanna Rantala; Muhammad Usman Rashid; Gad Rennert; Valerie Rhenius; Kerstin Rhiem; Harvey A Risch; Gus Rodriguez; Mary Anne Rossing; Anja Rudolph; Helga B Salvesen; Suleeporn Sangrajrang; Elinor J Sawyer; Joellen M Schildkraut; Marjanka K Schmidt; Rita K Schmutzler; Thomas A Sellers; Caroline Seynaeve; Mitul Shah; Chen Yang Shen; Xiao Ou Shu; Weiva Sieh; Christian F Singer; Olga M Sinilnikova; Susan Slager; Honglin Song; Penny Soucy; Melissa C Southey; Marie Stenmark-Askmalm; Dominique Stoppa-Lyonnet; Christian Sutter; Anthony Swerdlow; Sandrine Tchatchou; Manuel R Teixeira; Soo H Teo; Kathryn L Terry; Mary Beth Terry; Mads Thomassen; Maria Grazia Tibiletti; Laima Tihomirova; Silvia Tognazzo; Amanda Ewart Toland; Ian Tomlinson; Diana Torres; Thérèse Truong; Chiu Chen Tseng; Nadine Tung; Shelley S Tworoger; Celine Vachon; Ans M W Van Den Ouweland; Helena C Van Doorn; Elizabeth J Van Rensburg; Laura J Van't Veer; Adriaan Vanderstichele; Ignace Vergote; Joseph Vijai; Qin Wang; Shan Wang-Gohrke; Jeffrey N Weitzel; Nicolas Wentzensen; Alice S Whittemore; Hans Wildiers; Robert Winqvist; Anna H Wu; Drakoulis Yannoukakos; Sook Yee Yoon; Jyh Cherng Yu; Wei Zheng; Ying Zheng; Kum Kum Khanna; Jacques Simard; Alvaro N Monteiro; Juliet D French; Fergus J Couch; Matthew L Freedman; Douglas F Easton; Alison M Dunning; Paul D Pharoah; Stacey L Edwards; Georgia Chenevix-Trench; Antonis C Antoniou; Simon A Gayther; David Bowtell; Anna DeFazio; Penny Webb; Marie Agnès Collonge-Rame; Alexandre Damette; Emmanuelle Barouk-Simonet; Françoise Bonnet; Virginie Bubien; Nicolas Sevenet; Michel Longy; Pascaline Berthet; Dominique Vaur; Laurent Castera; Sandra Fert Ferrer; Yves Jean Bignon; Nancy Uhrhammer; Fanny Coron; Laurence Faivre; Amandine Baurand; Caroline Jacquot; Geoffrey Bertolone; Sarab Lizard; Dominique Leroux; Hélène Dreyfus; Christine Rebischung; Magalie Peysselon; Jean Philippe Peyrat; Joëlle Fournier; Françoise Révillion; Claude Adenis; Laurence Vénat-Bouvet; Mélanie Léone; Nadia Boutry-Kryza; Alain Calender; Sophie Giraud; Carole Verny-Pierre; Christine Lasset; Valérie Bonadona; Laure Barjhoux; Hagay Sobol; Violaine Bourdon; Tetsuro Noguchi; Audrey Remenieras; Isabelle Coupier; Pascal Pujol; Johanna Sokolowska; Myriam Bronner; Capucine Delnatte; Stéphane Bézieau; Véronique Mari; Marion Gauthier-Villars; Bruno Buecher; Etienne Rouleau; Lisa Golmard; Virginie Moncoutier; Muriel Belotti; Antoine De Pauw; Camille Elan; Emmanuelle Fourme; Anne Marie Birot; Claire Saule; Maïté Laurent; Claude Houdayer; Fabienne Lesueur; Noura Mebirouk; Florence Coulet; Chrystelle Colas; Florent Soubrier; Mathilde Warcoin; Fabienne Prieur; Marine Lebrun; Caroline Kientz; Danièle Muller; Jean Pierre Fricker; Christine Toulas; Rosine Guimbaud; Laurence Gladieff; Viviane Feillel; Isabelle Mortemousque; Brigitte Bressac-De-Paillerets; Olivier Caron; Marine Guillaud-Bataille; Helen Gregory; Zosia Miedzybrodzka; Patrick J Morrison; Alan Donaldson; Mark T Rogers; M. John Kennedy; Mary E Porteous; Angela Brady; Julian Barwell; Claire Foo; Fiona Lalloo; Lucy E Side; Jacqueline Eason; Alex Henderson; Lisa Walker; Jackie Cook; Katie Snape; Alex Murray; Emma McCann; M. A Rookus; F. E Van Leeuwen; L. E Van Der Kolk; M. K Schmidt; N. S Russell; J. L De Lange; R Wijnands; J. M Collée; M. J Hooning; C Seynaeve; C. H M Van Deurzen; I. M Obdeijn; C. J Van Asperen; R. A E M Tollenaar; T. C T E F Van Cronenburg; C. M Kets; M. G E M Ausems; C. C Van Der Pol; T. A M Van Os; Q Waisfisz; H. E J Meijers-Heijboer; E. B Gómez-Garcia; J. C Oosterwijk; M. J Mourits; G. H De Bock; H. F Vasen; S Siesling; J Verloop; L. I H Overbeek; Stephen Fox; Judy Kirk; Geoff Lindeman; Melanie Price

doi:10.1038/ncomms12675

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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Kate Lawrenson, Siddhartha Kar, Karen McCue, Karoline Kuchenbaeker, Kyriaki Michailidou, Jonathan Tyrer, Jonathan Beesley, Susan J Ramus, Qiyuan Li, Melissa K Delgado, …

07/09/2016

DOI: https://doi.org/10.1038/ncomms12675

Résumé

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.

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Titre: Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
Créateurs - sans rôle: Kate Lawrenson
Siddhartha Kar
Karen McCue
Karoline Kuchenbaeker
Kyriaki Michailidou
Jonathan Tyrer
Jonathan Beesley
Susan J Ramus
Qiyuan Li
Melissa K Delgado
Janet M Lee
Kristiina Aittomäki
Irene L Andrulis
Hoda Anton-Culver
Volker Arndt
Banu K Arun
Brita Arver
Elisa V Bandera
Monica Barile
Rosa B Barkardottir
Daniel Barrowdale
Matthias W Beckmann
Javier Benitez
Andrew Berchuck
Maria Bisogna
Line Bjorge
Carl Blomqvist
William Blot
Natalia Bogdanova
Anders Bojesen
Stig E Bojesen
Manjeet K Bolla
Bernardo Bonanni
Anne Lise Børresen-Dale
Hiltrud Brauch
Paul Brennan
Hermann Brenner
Fiona Bruinsma
Joan Brunet
Shaik Ahmad Buhari
Barbara Burwinkel
Ralf Butzow
Saundra S Buys
Qiuyin Cai
Trinidad Caldes
Ian Campbell
Rikki Canniotto
Jenny Chang-Claude
Jocelyne Chiquette
Ji Yeob Choi
Kathleen B M Claes
Linda S Cook
Angela Cox
Daniel W Cramer
Simon S Cross
Cezary Cybulski
Kamila Czene
Mary B Daly
Francesca Damiola
Agnieszka Dansonka-Mieszkowska
Hatef Darabi
Joe Dennis
Peter Devilee
Orland Diez
Jennifer A Doherty
Susan M Domchek
Cecilia M Dorfling
Thilo Dörk
Martine Dumont
Hans Ehrencrona
Bent Ejlertsen
Steve Ellis
Christoph Engel
Eunjung Lee
D. Gareth Evans
Peter A Fasching
Lidia Feliubadalo
Jonine Figueroa
Dieter Flesch-Janys
Olivia Fletcher
Henrik Flyger
Lenka Foretova
Florentia Fostira
William D Foulkes
Brooke L Fridley
Eitan Friedman
Debra Frost
Gaetana Gambino
Patricia A Ganz
Judy Garber
Montserrat García-Closas
Aleksandra Gentry-Maharaj
Maya Ghoussaini
Graham G Giles
Rosalind Glasspool
Andrew K Godwin
Mark S Goldberg
David E Goldgar
Anna González-Neira
Ellen L Goode
Marc T Goodman
Mark H Greene
Jacek Gronwald
Pascal Guénel
Christopher A Haiman
Per Hall
Emily Hallberg
Ute Hamann
Thomas V O Hansen
Patricia A Harrington
Mikael Hartman
Norhashimah Hassan
Sue Healey
Florian Heitz
Josef Herzog
Estrid Høgdall
Claus K Høgdall
Frans B L Hogervorst
Antoinette Hollestelle
John L Hopper
Peter J Hulick
Tomasz Huzarski
Evgeny N Imyanitov
Claudine Isaacs
Hidemi Ito
Anna Jakubowska
Ramunas Janavicius
Allan Jensen
Esther M John
Nichola Johnson
Maria Kabisch
Daehee Kang
Miroslav Kapuscinski
Beth Y Karlan
Sofia Khan
Lambertus A Kiemeney
Susanne Kruger Kjaer
Julia A Knight
Irene Konstantopoulou
Veli Matti Kosma
Vessela Kristensen
Jolanta Kupryjanczyk
Ava Kwong
Miguel De La Hoya
Yael Laitman
Diether Lambrechts
Nhu Le
Kim De Leeneer
Jenny Lester
Douglas A Levine
Jingmei Li
Annika Lindblom
Jirong Long
Artitaya Lophatananon
Jennifer T Loud
Karen Lu
Jan Lubinski
Arto Mannermaa
Siranoush Manoukian
Loic Le Marchand
Sara Margolin
Frederik Marme
Leon F A G Massuger
Keitaro Matsuo
Sylvie Mazoyer
Lesley McGuffog
Catriona McLean
Iain McNeish
Alfons Meindl
Usha Menon
Arjen R Mensenkamp
Roger L Milne
Marco Montagna
Kirsten B Moysich
Kenneth Muir
Anna Marie Mulligan
Katherine L Nathanson
Roberta B Ness
Susan L Neuhausen
Heli Nevanlinna
Silje Nord
Robert L Nussbaum
Kunle Odunsi
Kenneth Offit
Edith Olah
Olufunmilayo I Olopade
Janet E Olson
Curtis Olswold
David O'Malley
Irene Orlow
Nick Orr
Ana Osorio
Sue Kyung Park
Celeste L Pearce
Tanja Pejovic
Paolo Peterlongo
Georg Pfeiler
Catherine M Phelan
Elizabeth M Poole
Katri Pylkäs
Paolo Radice
Johanna Rantala
Muhammad Usman Rashid
Gad Rennert
Valerie Rhenius
Kerstin Rhiem
Harvey A Risch
Gus Rodriguez
Mary Anne Rossing
Anja Rudolph
Helga B Salvesen
Suleeporn Sangrajrang
Elinor J Sawyer
Joellen M Schildkraut
Marjanka K Schmidt
Rita K Schmutzler
Thomas A Sellers
Caroline Seynaeve
Mitul Shah
Chen Yang Shen
Xiao Ou Shu
Weiva Sieh
Christian F Singer
Olga M Sinilnikova
Susan Slager
Honglin Song
Penny Soucy
Melissa C Southey
Marie Stenmark-Askmalm
Dominique Stoppa-Lyonnet
Christian Sutter
Anthony Swerdlow
Sandrine Tchatchou
Manuel R Teixeira
Soo H Teo
Kathryn L Terry
Mary Beth Terry
Mads Thomassen
Maria Grazia Tibiletti
Laima Tihomirova
Silvia Tognazzo
Amanda Ewart Toland
Ian Tomlinson
Diana Torres
Thérèse Truong
Chiu Chen Tseng
Nadine Tung
Shelley S Tworoger
Celine Vachon
Ans M W Van Den Ouweland
Helena C Van Doorn
Elizabeth J Van Rensburg
Laura J Van't Veer
Adriaan Vanderstichele
Ignace Vergote
Joseph Vijai
Qin Wang
Shan Wang-Gohrke
Jeffrey N Weitzel
Nicolas Wentzensen
Alice S Whittemore
Hans Wildiers
Robert Winqvist
Anna H Wu
Drakoulis Yannoukakos
Sook Yee Yoon
Jyh Cherng Yu
Wei Zheng
Ying Zheng
Kum Kum Khanna
Jacques Simard
Alvaro N Monteiro
Juliet D French
Fergus J Couch
Matthew L Freedman
Douglas F Easton
Alison M Dunning
Paul D Pharoah
Stacey L Edwards
Georgia Chenevix-Trench
Antonis C Antoniou
Simon A Gayther
David Bowtell
Anna DeFazio
Penny Webb
Marie Agnès Collonge-Rame
Alexandre Damette
Emmanuelle Barouk-Simonet
Françoise Bonnet
Virginie Bubien
Nicolas Sevenet
Michel Longy
Pascaline Berthet
Dominique Vaur
Laurent Castera
Sandra Fert Ferrer
Yves Jean Bignon
Nancy Uhrhammer
Fanny Coron
Laurence Faivre
Amandine Baurand
Caroline Jacquot
Geoffrey Bertolone
Sarab Lizard
Dominique Leroux
Hélène Dreyfus
Christine Rebischung
Magalie Peysselon
Jean Philippe Peyrat
Joëlle Fournier
Françoise Révillion
Claude Adenis
Laurence Vénat-Bouvet
Mélanie Léone
Nadia Boutry-Kryza
Alain Calender
Sophie Giraud
Carole Verny-Pierre
Christine Lasset
Valérie Bonadona
Laure Barjhoux
Hagay Sobol
Violaine Bourdon
Tetsuro Noguchi
Audrey Remenieras
Isabelle Coupier
Pascal Pujol
Johanna Sokolowska
Myriam Bronner
Capucine Delnatte
Stéphane Bézieau
Véronique Mari
Marion Gauthier-Villars
Bruno Buecher
Etienne Rouleau
Lisa Golmard
Virginie Moncoutier
Muriel Belotti
Antoine De Pauw
Camille Elan
Emmanuelle Fourme
Anne Marie Birot
Claire Saule
Maïté Laurent
Claude Houdayer
Fabienne Lesueur
Noura Mebirouk
Florence Coulet
Chrystelle Colas
Florent Soubrier
Mathilde Warcoin
Fabienne Prieur
Marine Lebrun
Caroline Kientz
Danièle Muller
Jean Pierre Fricker
Christine Toulas
Rosine Guimbaud
Laurence Gladieff
Viviane Feillel
Isabelle Mortemousque
Brigitte Bressac-De-Paillerets
Olivier Caron
Marine Guillaud-Bataille
Helen Gregory
Zosia Miedzybrodzka
Patrick J Morrison
Alan Donaldson
Mark T Rogers
M. John Kennedy
Mary E Porteous
Angela Brady
Julian Barwell
Claire Foo
Fiona Lalloo
Lucy E Side
Jacqueline Eason
Alex Henderson
Lisa Walker
Jackie Cook
Katie Snape
Alex Murray
Emma McCann
M. A Rookus
F. E Van Leeuwen
L. E Van Der Kolk
M. K Schmidt
N. S Russell
J. L De Lange
R Wijnands
J. M Collée
M. J Hooning
C Seynaeve
C. H M Van Deurzen
I. M Obdeijn
C. J Van Asperen
R. A E M Tollenaar
T. C T E F Van Cronenburg
C. M Kets
M. G E M Ausems
C. C Van Der Pol
T. A M Van Os
Q Waisfisz
H. E J Meijers-Heijboer
E. B Gómez-Garcia
J. C Oosterwijk
M. J Mourits
G. H De Bock
H. F Vasen
S Siesling
J Verloop
L. I H Overbeek
Stephen Fox
Judy Kirk
Geoff Lindeman
Melanie Price
Identifiants: 99158951009311
Unité académique: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article