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Cancer Epidemiology, Biomarkers & Prevention
Cancer Epidemiology, Biomarkers & Prevention

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CEBP Focus

Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions

Siddhartha P. Kar, Andrew Berchuck, Simon A. Gayther, Ellen L. Goode, Kirsten B. Moysich, Celeste Leigh Pearce, Susan J. Ramus, Joellen M. Schildkraut, Thomas A. Sellers and Paul D.P. Pharoah
Siddhartha P. Kar
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
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  • For correspondence: sk718@medschl.cam.ac.ukpp10001@medschl.cam.ac.uk
Andrew Berchuck
Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina.
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Simon A. Gayther
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California.Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California.
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Ellen L. Goode
Department of Health Science Research, Division of Epidemiology, Mayo Clinic, Rochester, Minnesota.
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Kirsten B. Moysich
Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York.
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Celeste Leigh Pearce
Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, Michigan.
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Susan J. Ramus
School of Women's and Children's Health, University of New South Wales, Sydney, Australia.
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Joellen M. Schildkraut
Department of Public Health Sciences, University of Virginia School of Medicine, Virginia.
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Thomas A. Sellers
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida.
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Paul D.P. Pharoah
Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom.
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  • For correspondence: sk718@medschl.cam.ac.ukpp10001@medschl.cam.ac.uk
DOI: 10.1158/1055-9965.EPI-17-0315 Published April 2018
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Abstract

In this review, we summarize current progress in the genetic epidemiology of epithelial ovarian cancer (EOC), focusing exclusively on elucidating the role of common germline genetic variation in conferring susceptibility to EOC. We provide an overview of the more than 30 EOC risk loci identified to date by genome-wide association studies (GWAS) and describe the contribution of large-scale, cross-cancer type, custom genotyping projects, such as the OncoArray and the Collaborative Oncological Gene-Environment Study, to locus discovery and replication. We discuss the histotype-specific nature of these EOC risk loci, pleiotropy, or overlapping genetic effects between EOC and other hormone-related cancer types, and the application of findings to polygenic risk prediction for EOC. The second part of the article offers a concise review of primarily laboratory-based studies that have led to the identification of several putative EOC susceptibility genes using common variants at the known EOC risk loci as starting points. More global biological insights emerging from network- and pathway-based analyses of GWAS for EOC susceptibility are also highlighted. Finally, we delve into potential future directions, including the need to identify EOC risk loci in non-European populations and the next generation of GWAS functional studies that are likely to involve genome editing to establish the cell type–specific carcinogenic effects of EOC risk variants Cancer Epidemiol Biomarkers Prev; 27(4); 395–404. ©2018 AACR.

See all articles in this CEBP Focus section, “Genome-Wide Association Studies in Cancer.”

  • Received April 1, 2017.
  • Revision received May 24, 2017.
  • Accepted June 6, 2017.
  • Published first June 14, 2017.
  • ©2017 American Association for Cancer Research.
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Cancer Epidemiology Biomarkers & Prevention: 27 (4)
April 2018
Volume 27, Issue 4
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Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions
Siddhartha P. Kar, Andrew Berchuck, Simon A. Gayther, Ellen L. Goode, Kirsten B. Moysich, Celeste Leigh Pearce, Susan J. Ramus, Joellen M. Schildkraut, Thomas A. Sellers and Paul D.P. Pharoah
Cancer Epidemiol Biomarkers Prev April 1 2018 (27) (4) 395-404; DOI: 10.1158/1055-9965.EPI-17-0315

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Common Genetic Variation and Susceptibility to Ovarian Cancer: Current Insights and Future Directions
Siddhartha P. Kar, Andrew Berchuck, Simon A. Gayther, Ellen L. Goode, Kirsten B. Moysich, Celeste Leigh Pearce, Susan J. Ramus, Joellen M. Schildkraut, Thomas A. Sellers and Paul D.P. Pharoah
Cancer Epidemiol Biomarkers Prev April 1 2018 (27) (4) 395-404; DOI: 10.1158/1055-9965.EPI-17-0315
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    • Abstract
    • Introduction
    • GWASs of EOC Susceptibility
    • From Genetic Associations to Biological Mechanisms in Ovarian Cancer
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