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 Balmana; 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; Amanda Black; Kenneth Blankstein; Marinus J. Blok; Clara Bodelon; AOCS Study Group; EMEMBRACE Study; GEMO Study Collaborators; HEBON Study; KConFab Investigators; OPAL Study Grp; P Pujol

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 Balmana, 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, Amanda Black, Kenneth Blankstein, Marinus J. Blok, Clara Bodelon, AOCS Study Group, EMEMBRACE Study, GEMO Study Collaborators, HEBON Study, KConFab Investigators, OPAL Study Grp, P Pujol^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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
Pages (from-to)	680-691
Number of pages	12
Journal	Nature Genetics
Volume	49
Issue number	5
DOIs	https://doi.org/10.1038/ng.3826
Publication status	Published - May 2017

Keywords

CLEAR-CELL CARCINOMA
BREAST-CANCER
COMMON VARIANTS
TELOMERE LENGTH
RISK
ASSOCIATION
ENDOMETRIOSIS
METAANALYSIS
POPULATION
MUTATIONS

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10.1038/ng.3826

Cite this

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., ... Pujol, P. (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

@article{82c85658319048149530b0bb7a5e0f7f,

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 = "CLEAR-CELL CARCINOMA, BREAST-CANCER, COMMON VARIANTS, TELOMERE LENGTH, RISK, ASSOCIATION, ENDOMETRIOSIS, METAANALYSIS, POPULATION, MUTATIONS",

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 Balmana 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 Amanda Black and Kenneth Blankstein and Blok, {Marinus J.} and Clara Bodelon and {AOCS Study Group} and {EMEMBRACE Study} and {GEMO Study Collaborators} and {HEBON Study} and {KConFab Investigators} and {OPAL Study Grp} and P Pujol",

year = "2017",

month = may,

doi = "10.1038/ng.3826",

language = "English",

volume = "49",

pages = "680--691",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "5",

}

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, Balmana, J, Banerjee, SN, Barjhoux, L, Barkardottir, RB, Bean, Y, Beckmann, MW, Beeghly-Fadiel, A, Benitez, J, Bermisheva, M, Bernardini, MQ, Birrer, MJ, Bjorge, L, Black, A, Blankstein, K, Blok, MJ, Bodelon, C, AOCS Study Group, EMEMBRACE Study, GEMO Study Collaborators, HEBON Study, KConFab Investigators, OPAL Study Grp & Pujol, P 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

TY - JOUR

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 - Balmana, 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 - Blankstein, Kenneth

AU - Blok, Marinus J.

AU - Bodelon, Clara

AU - AOCS Study Group

AU - EMEMBRACE Study

AU - GEMO Study Collaborators

AU - HEBON Study

AU - KConFab Investigators

AU - OPAL Study Grp

AU - Pujol, P

PY - 2017/5

Y1 - 2017/5

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 - CLEAR-CELL CARCINOMA

KW - BREAST-CANCER

KW - COMMON VARIANTS

KW - TELOMERE LENGTH

KW - RISK

KW - ASSOCIATION

KW - ENDOMETRIOSIS

KW - METAANALYSIS

KW - POPULATION

KW - MUTATIONS

U2 - 10.1038/ng.3826

DO - 10.1038/ng.3826

M3 - Article

C2 - 28346442

SN - 1061-4036

VL - 49

SP - 680

EP - 691

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -