Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus.
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Date
2016-09-07Author
Lawrenson, K
Kar, S
McCue, K
Kuchenbaeker, K
Michailidou, K
Tyrer, J
Beesley, J
Ramus, SJ
Li, Q
Delgado, MK
Lee, JM
Aittomäki, K
Andrulis, IL
Anton-Culver, H
Arndt, V
Arun, BK
Arver, B
Bandera, EV
Barile, M
Barkardottir, RB
Barrowdale, D
Beckmann, MW
Benitez, J
Berchuck, A
Bisogna, M
Bjorge, L
Blomqvist, C
Blot, W
Bogdanova, N
Bojesen, A
Bojesen, SE
Bolla, MK
Bonanni, B
Børresen-Dale, A-L
Brauch, H
Brennan, P
Brenner, H
Bruinsma, F
Brunet, J
Buhari, SA
Burwinkel, B
Butzow, R
Buys, SS
Cai, Q
Caldes, T
Campbell, I
Canniotto, R
Chang-Claude, J
Chiquette, J
Choi, J-Y
Claes, KBM
GEMO Study Collaborators,
Cook, LS
Cox, A
Cramer, DW
Cross, SS
Cybulski, C
Czene, K
Daly, MB
Damiola, F
Dansonka-Mieszkowska, A
Darabi, H
Dennis, J
Devilee, P
Diez, O
Doherty, JA
Domchek, SM
Dorfling, CM
Dörk, T
Dumont, M
Ehrencrona, H
Ejlertsen, B
Ellis, S
EMBRACE,
Engel, C
Lee, E
Evans, DG
Fasching, PA
Feliubadalo, L
Figueroa, J
Flesch-Janys, D
Fletcher, O
Flyger, H
Foretova, L
Fostira, F
Foulkes, WD
Fridley, BL
Friedman, E
Frost, D
Gambino, G
Ganz, PA
Garber, J
García-Closas, M
Gentry-Maharaj, A
Ghoussaini, M
Giles, GG
Glasspool, R
Godwin, AK
Goldberg, MS
Goldgar, DE
González-Neira, A
Goode, EL
Goodman, MT
Greene, MH
Gronwald, J
Guénel, P
Haiman, CA
Hall, P
Hallberg, E
Hamann, U
Hansen, TVO
Harrington, PA
Hartman, M
Hassan, N
Healey, S
Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON),
Heitz, F
Herzog, J
Høgdall, E
Høgdall, CK
Hogervorst, FBL
Hollestelle, A
Hopper, JL
Hulick, PJ
Huzarski, T
Imyanitov, EN
KConFab Investigators,
Australian Ovarian Cancer Study Group,
Isaacs, C
Ito, H
Jakubowska, A
Janavicius, R
Jensen, A
John, EM
Johnson, N
Kabisch, M
Kang, D
Kapuscinski, M
Karlan, BY
Khan, S
Kiemeney, LA
Kjaer, SK
Knight, JA
Konstantopoulou, I
Kosma, V-M
Kristensen, V
Kupryjanczyk, J
Kwong, A
de la Hoya, M
Laitman, Y
Lambrechts, D
Le, N
De Leeneer, K
Lester, J
Levine, DA
Li, J
Lindblom, A
Long, J
Lophatananon, A
Loud, JT
Lu, K
Lubinski, J
Mannermaa, A
Manoukian, S
Le Marchand, L
Margolin, S
Marme, F
Massuger, LFAG
Matsuo, K
Mazoyer, S
McGuffog, L
McLean, C
McNeish, I
Meindl, A
Menon, U
Mensenkamp, AR
Milne, RL
Montagna, M
Moysich, KB
Muir, K
Mulligan, AM
Nathanson, KL
Ness, RB
Neuhausen, SL
Nevanlinna, H
Nord, S
Nussbaum, RL
Odunsi, K
Offit, K
Olah, E
Olopade, OI
Olson, JE
Olswold, C
O'Malley, D
Orlow, I
Orr, N
Osorio, A
Park, SK
Pearce, CL
Pejovic, T
Peterlongo, P
Pfeiler, G
Phelan, CM
Poole, EM
Pylkäs, K
Radice, P
Rantala, J
Rashid, MU
Rennert, G
Rhenius, V
Rhiem, K
Risch, HA
Rodriguez, G
Rossing, MA
Rudolph, A
Salvesen, HB
Sangrajrang, S
Sawyer, EJ
Schildkraut, JM
Schmidt, MK
Schmutzler, RK
Sellers, TA
Seynaeve, C
Shah, M
Shen, C-Y
Shu, X-O
Sieh, W
Singer, CF
Sinilnikova, OM
Slager, S
Song, H
Soucy, P
Southey, MC
Stenmark-Askmalm, M
Stoppa-Lyonnet, D
Sutter, C
Swerdlow, A
Tchatchou, S
Teixeira, MR
Teo, SH
Terry, KL
Terry, MB
Thomassen, M
Tibiletti, MG
Tihomirova, L
Tognazzo, S
Toland, AE
Tomlinson, I
Torres, D
Truong, T
Tseng, C-C
Tung, N
Tworoger, SS
Vachon, C
van den Ouweland, AMW
van Doorn, HC
van Rensburg, EJ
Van't Veer, LJ
Vanderstichele, A
Vergote, I
Vijai, J
Wang, Q
Wang-Gohrke, S
Weitzel, JN
Wentzensen, N
Whittemore, AS
Wildiers, H
Winqvist, R
Wu, AH
Yannoukakos, D
Yoon, S-Y
Yu, J-C
Zheng, W
Zheng, Y
Khanna, KK
Simard, J
Monteiro, AN
French, JD
Couch, FJ
Freedman, ML
Easton, DF
Dunning, AM
Pharoah, PD
Edwards, SL
Chenevix-Trench, G
Antoniou, AC
Gayther, SA
Type
Journal Article
Metadata
Show full item recordAbstract
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.
xmlui.dri2xhtml.METS-1.0.item-oa-location
http://www.ncbi.nlm.nih.gov/pubmed/27601076Collections
Subject
GEMO Study Collaborators
EMBRACE
Hereditary Breast and Ovarian Cancer Research Group Netherlands (HEBON)
KConFab Investigators
Australian Ovarian Cancer Study Group
Chromosomes, Human, Pair 19
Humans
Breast Neoplasms
Ovarian Neoplasms
Genetic Predisposition to Disease
RNA, Messenger
Genotype
Polymorphism, Single Nucleotide
Alleles
African Continental Ancestry Group
Asian Continental Ancestry Group
Female
Genome-Wide Association Study
Research team
Complex Trait Genetics
Functional Genetic Epidemiology
Aetiological Epidemiology
Language
eng
Date accepted
2016-07-20
License start date
2016-09-07
Citation
Nature communications, 2016, 7 pp. 12675 - ?
Publisher
NATURE PORTFOLIO
Except where otherwise noted, this item's license is described
as
https://creativecommons.org/licenses/by/4.0
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