TY - JOUR
T1 - Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
AU - AOCS study group
AU - EMBRACE Study
AU - OPAL study group
AU - KConFab investigators
AU - GEMO Study Collaborators
AU - HEBON Study
AU - Phelan, Catherine M.
AU - Kuchenbaecker, Karoline B.
AU - Tyrer, Jonathan P.
AU - Kar, Siddhartha P.
AU - Lawrenson, Kate
AU - Winham, Stacey J.
AU - Dennis, Joe
AU - Pirie, Ailith
AU - Riggan, Marjorie J.
AU - Chornokur, Ganna
AU - Earp, Madalene A.
AU - Lyra, Paulo C.
AU - Lee, Janet M.
AU - Coetzee, Simon
AU - Beesley, Jonathan
AU - McGuffog, Lesley
AU - Soucy, Penny
AU - Dicks, Ed
AU - Lee, Andrew
AU - Barrowdale, Daniel
AU - Lecarpentier, Julie
AU - Leslie, Goska
AU - Aalfs, Cora M.
AU - Aben, Katja K.H.
AU - Adams, Marcia
AU - Adlard, Julian
AU - Andrulis, Irene L.
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia
AU - Aravantinos, Gerasimos
AU - Arnold, Norbert
AU - Arun, Banu K.
AU - Arver, Brita
AU - Azzollini, Jacopo
AU - Balmaña, Judith
AU - Banerjee, Susana N.
AU - Barjhoux, Laure
AU - Barkardottir, Rosa B.
AU - Bean, Yukie
AU - Beckmann, Matthias W.
AU - Beeghly-Fadiel, Alicia
AU - Benitez, Javier
AU - Bermisheva, Marina
AU - Bernardini, Marcus Q.
AU - Birrer, Michael J.
AU - Bjorge, Line
AU - Black, Amanda
AU - Cunningham, Julie M.
AU - Couch, Fergus J.
AU - Goode, Ellen L.
N1 - Funding Information:
The OCAC OncoArray genotyping project was funded through grants from the US National Institutes of Health (CA1X01HG007491-01 (C.I.A.), U19-CA148112 (T.A.S.), R01-CA149429 (C.M.P.) and R01-CA058598 (M.T.G.)); Canadian Institutes of Health Research (MOP-86727 (L.E.K.)); and the Ovarian Cancer Research Fund (A.B.). Funding for the CIMBA OncoArray genotyping was provided by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministère de l'Économie, de la Science et de l'Innovation du Québec through Génome Québec, the Quebec Breast Cancer Foundation for the PERSPECTIVE project, the US National Institutes of Health (CA1X01HG007491-01 (C.I.A.)), the Odense University Hospital Research Foundation (M.T.), the National R&D Program for Cancer Control, Ministry of Health and Welfare, Republic of Korea (1420190 (S.K.P.)), the Italian Association for Cancer Research (IG16933 (L.O.)) and German Cancer Aid (110837 (R.K.S.). Funding sources for the contributing studies are provided in the Supplementary Note. We pay special tribute to the contribution of Brian Henderson to the GAME-ON consortium and to Olga M. Sinilnikova for her contribution to CIMBA and for her part in the initiation and coordination of GEMO until she sadly passed away on 30 June 2014. We thank the study participants, doctors, nurses, clinical and scientific collaborators, healthcare providers and health information sources that have contributed to the many studies contributing to this manuscript. A full list is provided in the Supplementary Note.
Publisher Copyright:
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved.
PY - 2017/5/1
Y1 - 2017/5/1
N2 - To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
AB - To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC.
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U2 - 10.1038/ng.3826
DO - 10.1038/ng.3826
M3 - Article
C2 - 28346442
AN - SCOPUS:85016117389
SN - 1061-4036
VL - 49
SP - 680
EP - 691
JO - Nature Genetics
JF - Nature Genetics
IS - 5
ER -