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

Catherine M Phelan; Karoline B Kuchenbaecker; Jonathan P Tyrer; Siddhartha P Kar; Kate Lawrenson; Stacey J Winham; Joe Dennis; Ailith Pirie; Marjorie J Riggan; Ganna Chornokur; Madalene A Earp; Paulo C Lyra; Janet M Lee; Simon Coetzee; Jonathan Beesley; Lesley McGuffog; Penny Soucy; Ed Dicks; Andrew Lee; Daniel Barrowdale; Julie Lecarpentier; Goska Leslie; Cora M Aalfs; Katja K H Aben; Marcia Adams; Julian Adlard; Irene L Andrulis; Hoda Anton-Culver; Natalia Antonenkova; Gerasimos Aravantinos; Norbert Arnold; Banu K Arun; Brita Arver; Jacopo Azzollini; Judith Balmaña; Susana N Banerjee; Laure Barjhoux; Rosa B Barkardottir; Yukie Bean; Matthias W Beckmann; Alicia Beeghly-Fadiel; Javier Benitez; Marina Bermisheva; Marcus Q Bernardini; Michael J Birrer; Line Bjorge; Anne-Marie Gerdes; Claus K Høgdall; Estrid Høgdall; Susanne K Kjaer; AOCS Study Group

doi:10.1038/ng.3826

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

Catherine M Phelan, Karoline B Kuchenbaecker, Jonathan P Tyrer, Siddhartha P Kar, Kate Lawrenson, Stacey J Winham, Joe Dennis, Ailith Pirie, Marjorie J Riggan, Ganna Chornokur, Madalene A Earp, Paulo C Lyra, Janet M Lee, Simon Coetzee, Jonathan Beesley, Lesley McGuffog, Penny Soucy, Ed Dicks, Andrew Lee, Daniel BarrowdaleJulie Lecarpentier, Goska Leslie, Cora M Aalfs, Katja K H Aben, Marcia Adams, Julian Adlard, Irene L Andrulis, Hoda Anton-Culver, Natalia Antonenkova, Gerasimos Aravantinos, Norbert Arnold, Banu K Arun, Brita Arver, Jacopo Azzollini, Judith Balmaña, Susana N Banerjee, Laure Barjhoux, Rosa B Barkardottir, Yukie Bean, Matthias W Beckmann, Alicia Beeghly-Fadiel, Javier Benitez, Marina Bermisheva, Marcus Q Bernardini, Michael J Birrer, Line Bjorge, Anne-Marie Gerdes, Claus K Høgdall, Estrid Høgdall, Susanne K Kjaer, AOCS Study Group

Department of Clinical Medicine

118 Citations (Scopus)

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.

Original language	English
Journal	Nature Genetics
Volume	49
Issue number	5
Pages (from-to)	680-691
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3826
Publication status	Published - 1 May 2017

Keywords

Alleles
BRCA1 Protein
BRCA2 Protein
Female
Genetic Loci
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Meta-Analysis as Topic
Mutation
Neoplasms, Glandular and Epithelial
Ovarian Neoplasms
Polymorphism, Single Nucleotide
Risk Factors
Telomere-Binding Proteins
Journal Article

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Phelan, C. M., Kuchenbaecker, K. B., Tyrer, J. P., Kar, S. P., Lawrenson, K., Winham, S. J., Dennis, J., Pirie, A., Riggan, M. J., Chornokur, G., Earp, M. A., Lyra, P. C., Lee, J. M., Coetzee, S., Beesley, J., McGuffog, L., Soucy, P., Dicks, E., Lee, A., ... AOCS Study Group (2017). Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nature Genetics, 49(5), 680-691. https://doi.org/10.1038/ng.3826

Phelan, CM, Kuchenbaecker, KB, Tyrer, JP, Kar, SP, Lawrenson, K, Winham, SJ, Dennis, J, Pirie, A, Riggan, MJ, Chornokur, G, Earp, MA, Lyra, PC, Lee, JM, Coetzee, S, Beesley, J, McGuffog, L, Soucy, P, Dicks, E, Lee, A, Barrowdale, D, Lecarpentier, J, Leslie, G, Aalfs, CM, Aben, KKH, Adams, M, Adlard, J, Andrulis, IL, Anton-Culver, H, Antonenkova, N, Aravantinos, G, Arnold, N, Arun, BK, Arver, B, Azzollini, J, Balmaña, J, Banerjee, SN, Barjhoux, L, Barkardottir, RB, Bean, Y, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Birrer, MJ, Bjorge, L, Gerdes, A-M , Høgdall, CK , Høgdall, E , Kjaer, SK & AOCS Study Group 2017, 'Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer', Nature Genetics, vol. 49, no. 5, pp. 680-691. https://doi.org/10.1038/ng.3826

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title = "Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer",

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.",

keywords = "Alleles, BRCA1 Protein, BRCA2 Protein, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Meta-Analysis as Topic, Mutation, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Polymorphism, Single Nucleotide, Risk Factors, Telomere-Binding Proteins, Journal Article",

author = "Phelan, {Catherine M} and Kuchenbaecker, {Karoline B} and Tyrer, {Jonathan P} and Kar, {Siddhartha P} and Kate Lawrenson and Winham, {Stacey J} and Joe Dennis and Ailith Pirie and Riggan, {Marjorie J} and Ganna Chornokur and Earp, {Madalene A} and Lyra, {Paulo C} and Lee, {Janet M} and Simon Coetzee and Jonathan Beesley and Lesley McGuffog and Penny Soucy and Ed Dicks and Andrew Lee and Daniel Barrowdale and Julie Lecarpentier and Goska Leslie and Aalfs, {Cora M} and Aben, {Katja K H} and Marcia Adams and Julian Adlard and Andrulis, {Irene L} and Hoda Anton-Culver and Natalia Antonenkova and Gerasimos Aravantinos and Norbert Arnold and Arun, {Banu K} and Brita Arver and Jacopo Azzollini and Judith Balma{\~n}a and Banerjee, {Susana N} and Laure Barjhoux and Barkardottir, {Rosa B} and Yukie Bean and Beckmann, {Matthias W} and Alicia Beeghly-Fadiel and Javier Benitez and Marina Bermisheva and Bernardini, {Marcus Q} and Birrer, {Michael J} and Line Bjorge and Anne-Marie Gerdes and H{\o}gdall, {Claus K} and Estrid H{\o}gdall and Kjaer, {Susanne K} and {AOCS Study Group}",

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T1 - Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer

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 - Gerdes, Anne-Marie

AU - Høgdall, Claus K

AU - Høgdall, Estrid

AU - Kjaer, Susanne K

AU - AOCS Study Group

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.

KW - Alleles

KW - BRCA1 Protein

KW - BRCA2 Protein

KW - Female

KW - Genetic Loci

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Meta-Analysis as Topic

KW - Mutation

KW - Neoplasms, Glandular and Epithelial

KW - Ovarian Neoplasms

KW - Polymorphism, Single Nucleotide

KW - Risk Factors

KW - Telomere-Binding Proteins

KW - Journal Article

U2 - 10.1038/ng.3826

DO - 10.1038/ng.3826

M3 - Journal article

C2 - 28346442

SN - 1061-4036

VL - 49

SP - 680

EP - 691

JO - Nature: New biology

JF - Nature: New biology

IS - 5

ER -

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

Abstract

Keywords

UN SDGs

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