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Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer
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.
1061-4036
680-691
Eccles, Diana
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Phelan, Catherine M.
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Kuchenbaecker, Karoline B.
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Tyrer, Jonathan P.
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Kar, Siddhartha
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Lawrenson, Kate
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Winham, Stacey J.
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Dennis, Joe
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Pirie, Ailith
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Riggan, Marjorie J.
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Chornokur, Ganna
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Earp, Madalene A.
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Lyra Jr., Paulo C.
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Lee, Janet M.
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Coetzee, Simon
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Beesley, Jonathan
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McGuffog, Lesley
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Soucy, Penny
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Dicks, Ed
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Lee, Andrew
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Barrowdale, Daniel
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Lecarpentier, Julie
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Goska, Leslie
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Aalfs, Cora M.
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Aben, Katja K.H.
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Adams, Marcia
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Adlard, Julian
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Andrulis, Irene L.
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Anton-Culver, Hoda
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Antonenkova, Natalia
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AOCS study Group
EMBRACE Study
GEMO Study Collaborators
HEBON Study
KConFab Investigators
OPAL study group
Eccles, Diana
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Phelan, Catherine M.
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Kuchenbaecker, Karoline B.
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Tyrer, Jonathan P.
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Kar, Siddhartha
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Lawrenson, Kate
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Winham, Stacey J.
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Dennis, Joe
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Pirie, Ailith
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Riggan, Marjorie J.
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Chornokur, Ganna
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Earp, Madalene A.
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Lyra Jr., Paulo C.
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Lee, Janet M.
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Coetzee, Simon
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Beesley, Jonathan
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McGuffog, Lesley
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Soucy, Penny
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Dicks, Ed
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Lee, Andrew
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Barrowdale, Daniel
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Lecarpentier, Julie
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Goska, Leslie
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Aalfs, Cora M.
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Aben, Katja K.H.
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Adams, Marcia
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Adlard, Julian
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Andrulis, Irene L.
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Anton-Culver, Hoda
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Antonenkova, Natalia
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Phelan, Catherine M., Kuchenbaecker, Karoline B., Tyrer, Jonathan P., Kar, Siddhartha, Lawrenson, Kate, Winham, Stacey J., Dennis, Joe, Pirie, Ailith, Riggan, Marjorie J., Chornokur, Ganna, Earp, Madalene A., Lyra Jr., Paulo C., Lee, Janet M., Coetzee, Simon, Beesley, Jonathan, McGuffog, Lesley, Soucy, Penny, Dicks, Ed, Lee, Andrew, Barrowdale, Daniel, Lecarpentier, Julie, Goska, Leslie, Aalfs, Cora M., Aben, Katja K.H., Adams, Marcia, Adlard, Julian, Andrulis, Irene L., Anton-Culver, Hoda and Antonenkova, Natalia , AOCS study Group, EMBRACE Study, GEMO Study Collaborators, HEBON Study, KConFab Investigators and OPAL study group (2017) Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nature Genetics, 49, 680-691. (doi:10.1038/ng.3826).

Record type: Article

Abstract

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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Accepted/In Press date: 3 March 2017
e-pub ahead of print date: 27 March 2017
Published date: May 2017

Identifiers

Local EPrints ID: 413505
URI: http://eprints.soton.ac.uk/id/eprint/413505
DOI: doi:10.1038/ng.3826
ISSN: 1061-4036
PURE UUID: f971173c-7a9a-4e84-9ffe-71a3a8465651
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 25 Aug 2017 16:31
Last modified: 16 Mar 2024 02:39

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Contributors

Author: Diana Eccles ORCID iD
Author: Catherine M. Phelan
Author: Karoline B. Kuchenbaecker
Author: Jonathan P. Tyrer
Author: Siddhartha Kar
Author: Kate Lawrenson
Author: Stacey J. Winham
Author: Joe Dennis
Author: Ailith Pirie
Author: Marjorie J. Riggan
Author: Ganna Chornokur
Author: Madalene A. Earp
Author: Paulo C. Lyra Jr.
Author: Janet M. Lee
Author: Simon Coetzee
Author: Jonathan Beesley
Author: Lesley McGuffog
Author: Penny Soucy
Author: Ed Dicks
Author: Andrew Lee
Author: Daniel Barrowdale
Author: Julie Lecarpentier
Author: Leslie Goska
Author: Cora M. Aalfs
Author: Katja K.H. Aben
Author: Marcia Adams
Author: Julian Adlard
Author: Irene L. Andrulis
Author: Hoda Anton-Culver
Author: Natalia Antonenkova
Corporate Author: AOCS study Group
Corporate Author: EMBRACE Study
Corporate Author: GEMO Study Collaborators
Corporate Author: HEBON Study
Corporate Author: KConFab Investigators
Corporate Author: OPAL study group

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