Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12530/25319
Title: Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.
Authors: 
Lawrenson, Kate
Kar, Siddhartha
McCue, Karen
Kuchenbaeker, Karoline
Michailidou, Kyriaki
Tyrer, Jonathan
Beesley, Jonathan
Ramus, Susan J
Li, Qiyuan
Delgado, Melissa K
Lee, Janet M
Aittomäki, Kristiina
Andrulis, Irene L
Anton-Culver, Hoda
Arndt, Volker
Arun, Banu K
Arver, Brita
Bandera, Elisa V
Barile, Monica
Barkardottir, Rosa B
Barrowdale, Daniel
Beckmann, Matthias W
Benitez, Javier
Berchuck, Andrew
Bisogna, Maria
Bjorge, Line
Blomqvist, Carl
Blot, William
Bogdanova, Natalia
Bojesen, Anders
Bojesen, Stig E
Bolla, Manjeet K
Bonanni, Bernardo
Børresen-Dale, Anne-Lise
Brauch, Hiltrud
Brennan, Paul
Brenner, Hermann
Bruinsma, Fiona
Brunet, Joan
Buhari, Shaik Ahmad
Burwinkel, Barbara
Butzow, Ralf
Buys, Saundra S
Cai, Qiuyin
Caldes, Trinidad
Campbell, Ian
Canniotto, Rikki
Chang-Claude, Jenny
Chiquette, Jocelyne
Choi, Ji-Yeob
Claes, Kathleen B M
Cook, Linda S
Cox, Angela
Cramer, Daniel W
Cross, Simon S
Cybulski, Cezary
Czene, Kamila
Daly, Mary B
Damiola, Francesca
Dansonka-Mieszkowska, Agnieszka
Darabi, Hatef
Dennis, Joe
Devilee, Peter
Diez, Orland
Doherty, Jennifer A
Domchek, Susan M
Dorfling, Cecilia M
Dörk, Thilo
Dumont, Martine
Ehrencrona, Hans
Ejlertsen, Bent
Ellis, Steve
Engel, Christoph
Lee, Eunjung
Evans, D Gareth
Fasching, Peter A
Feliubadalo, Lidia
Figueroa, Jonine
Flesch-Janys, Dieter
Fletcher, Olivia
Flyger, Henrik
Foretova, Lenka
Fostira, Florentia
Foulkes, William D
Fridley, Brooke L
Friedman, Eitan
Frost, Debra
Gambino, Gaetana
Ganz, Patricia A
Garber, Judy
García-Closas, Montserrat
Gentry-Maharaj, Aleksandra
Ghoussaini, Maya
Giles, Graham G
Glasspool, Rosalind
Godwin, Andrew K
Goldberg, Mark S
Goldgar, David E
González-Neira, Anna
Goode, Ellen L
Goodman, Marc T
Greene, Mark H
Gronwald, Jacek
Guénel, Pascal
Haiman, Christopher A
Hall, Per
Hallberg, Emily
Hamann, Ute
Hansen, Thomas V O
Harrington, Patricia A
Hartman, Mikael
Hassan, Norhashimah
Healey, Sue
Heitz, Florian
Herzog, Josef
Høgdall, Estrid
Høgdall, Claus K
Hogervorst, Frans B L
Hollestelle, Antoinette
Hopper, John L
Hulick, Peter J
Huzarski, Tomasz
Imyanitov, Evgeny N
Isaacs, Claudine
Ito, Hidemi
Jakubowska, Anna
Janavicius, Ramunas
Jensen, Allan
John, Esther M
Johnson, Nichola
Kabisch, Maria
Kang, Daehee
Kapuscinski, Miroslav
Karlan, Beth Y
Khan, Sofia
Kiemeney, Lambertus A
Kjaer, Susanne Kruger
Knight, Julia A
Konstantopoulou, Irene
Kosma, Veli-Matti
Kristensen, Vessela
Kupryjanczyk, Jolanta
Kwong, Ava
de la Hoya, Miguel
Laitman, Yael
Lambrechts, Diether
Le, Nhu
De Leeneer, Kim
Lester, Jenny
Levine, Douglas A
Li, Jingmei
Lindblom, Annika
Long, Jirong
Lophatananon, Artitaya
Loud, Jennifer T
Lu, Karen
Lubinski, Jan
Mannermaa, Arto
Manoukian, Siranoush
Le Marchand, Loic
Margolin, Sara
Marme, Frederik
Massuger, Leon F A G
Matsuo, Keitaro
Mazoyer, Sylvie
McGuffog, Lesley
McLean, Catriona
McNeish, Iain
Meindl, Alfons
Menon, Usha
Mensenkamp, Arjen R
Milne, Roger L
Montagna, Marco
Moysich, Kirsten B
Muir, Kenneth
Mulligan, Anna Marie
Nathanson, Katherine L
Ness, Roberta B
Neuhausen, Susan L
Nevanlinna, Heli
Nord, Silje
Nussbaum, Robert L
Odunsi, Kunle
Offit, Kenneth
Olah, Edith
Olopade, Olufunmilayo I
Olson, Janet E
Olswold, Curtis
O'Malley, David
Orlow, Irene
Orr, Nick
Osorio, Ana
Park, Sue Kyung
Pearce, Celeste L
Pejovic, Tanja
Peterlongo, Paolo
Pfeiler, Georg
Phelan, Catherine M
Poole, Elizabeth M
Pylkäs, Katri
Radice, Paolo
Rantala, Johanna
Rashid, Muhammad Usman
Rennert, Gad
Rhenius, Valerie
Rhiem, Kerstin
Risch, Harvey A
Rodriguez, Gus
Rossing, Mary Anne
Rudolph, Anja
Salvesen, Helga B
Sangrajrang, Suleeporn
Sawyer, Elinor J
Schildkraut, Joellen M
Schmidt, Marjanka K
Schmutzler, Rita K
Sellers, Thomas A
Seynaeve, Caroline
Shah, Mitul
Shen, Chen-Yang
Shu, Xiao-Ou
Sieh, Weiva
Singer, Christian F
Sinilnikova, Olga M
Slager, Susan
Song, Honglin
Soucy, Penny
Southey, Melissa C
Stenmark-Askmalm, Marie
Stoppa-Lyonnet, Dominique
Sutter, Christian
Swerdlow, Anthony
Tchatchou, Sandrine
Teixeira, Manuel R
Teo, Soo H
Terry, Kathryn L
Terry, Mary Beth
Thomassen, Mads
Tibiletti, Maria Grazia
Tihomirova, Laima
Tognazzo, Silvia
Toland, Amanda Ewart
Tomlinson, Ian
Torres, Diana
Truong, Thérèse
Tseng, Chiu-Chen
Tung, Nadine
Tworoger, Shelley S
Vachon, Celine
van den Ouweland, Ans M W
van Doorn, Helena C
van Rensburg, Elizabeth J
Van't Veer, Laura J
Vanderstichele, Adriaan
Vergote, Ignace
Vijai, Joseph
Wang, Qin
Wang-Gohrke, Shan
Weitzel, Jeffrey N
Wentzensen, Nicolas
Whittemore, Alice S
Wildiers, Hans
Winqvist, Robert
Wu, Anna H
Yannoukakos, Drakoulis
Yoon, Sook-Yee
Yu, Jyh-Cherng
Zheng, Wei
Zheng, Ying
Khanna, Kum Kum
Simard, Jacques
Monteiro, Alvaro N
French, Juliet D
Couch, Fergus J
Freedman, Matthew L
Easton, Douglas F
Dunning, Alison M
Pharoah, Paul D
Edwards, Stacey L
Chenevix-Trench, Georgia
Antoniou, Antonis C
Gayther, Simon A
Mesh: 
Issue Date: 2016
Citation: Nat Commun.2016 09;(7):12675
Abstract: 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.
PMID: 27601076
URI: https://hdl.handle.net/20.500.12530/25319
Rights: openAccess
Appears in Collections:Fundaciones e Institutos de Investigación > IIS H. U. Clínico San Carlos > Artículos

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