TY - JOUR
T1 - Identification of six new susceptibility loci for invasive epithelial ovarian cancer
AU - EMBRACE
AU - GEMO Study Collaborators
AU - Breast cancer Family Registry
AU - HEBON
AU - KConFab Investigators
AU - Australian cancer study (ovarian cancer Investigators)
AU - Australian Ovarian Cancer Study Group
AU - consortium of Investigators of modifiers of BRCA1 and BRCA2
AU - Kuchenbaecker, Karoline B.
AU - Ramus, Susan J.
AU - Tyrer, Jonathan
AU - Lee, Andrew
AU - Shen, Howard C.
AU - Beesley, Jonathan
AU - Lawrenson, Kate
AU - McGuffog, Lesley
AU - Healey, Sue
AU - Lee, Janet M.
AU - Spindler, Tassja J.
AU - Lin, Yvonne G.
AU - Pejovic, Tanja
AU - Bean, Yukie
AU - Li, Qiyuan
AU - Coetzee, Simon
AU - Hazelett, Dennis
AU - Miron, Alexander
AU - Southey, Melissa
AU - Terry, Mary Beth
AU - Goldgar, David E.
AU - Buys, Saundra S.
AU - Janavicius, Ramunas
AU - Dorfling, Cecilia M.
AU - Van Rensburg, Elizabeth J.
AU - Neuhausen, Susan L.
AU - Ding, Yuan Chun
AU - Hansen, Thomas V.O.
AU - Jønson, Lars
AU - Gerdes, Anne Marie
AU - Ejlertsen, Bent
AU - Barrowdale, Daniel
AU - Dennis, Joe
AU - Benitez, Javier
AU - Osorio, Ana
AU - Garcia, Maria Jose
AU - Komenaka, Ian
AU - Weitzel, Jeffrey N.
AU - Ganschow, Pamela
AU - Peterlongo, Paolo
AU - Bernard, Loris
AU - Viel, Alessandra
AU - Bonanni, Bernardo
AU - Peissel, Bernard
AU - Manoukian, Siranoush
AU - Radice, Paolo
AU - Papi, Laura
AU - Ottini, Laura
AU - Fostira, Florentia
AU - Gayther, Simon
N1 - Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
AB - Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10 â+'8. Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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U2 - 10.1038/ng.3185
DO - 10.1038/ng.3185
M3 - Article
C2 - 25581431
AN - SCOPUS:84929171835
SN - 1061-4036
VL - 47
SP - 164
EP - 171
JO - Nature Genetics
JF - Nature Genetics
IS - 2
ER -