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

Accepted version
Peer-reviewed

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Type

Article

Change log

Authors

Kar, Siddhartha P 
Berchuck, Andrew 
Gayther, Simon A 
Goode, Ellen L 
Moysich, Kirsten B 

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.

Description

Keywords

epithelial ovarian cancer, genome-wide association studies, post-GWAS functional studies

Journal Title

Cancer Epidemiology, Biomarkers & Prevention

Conference Name

Journal ISSN

1055-9965
1538-7755

Volume Title

Publisher

American Association for Cancer Research
Sponsorship
Cancer Research Uk (None)
Cancer Research Uk (None)
S. P. K. is supported by a Homerton College Junior Research Fellowship.