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

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Kar, SP; Berchuck, A; Gayther, SA; Goode, EL; Moysich, KB; Pearce, CL; Ramus, SJ; Schildkraut, JM; Sellers, TA; Pharoah, PDP

Published Date

  • June 14, 2017

Published In

PubMed ID

  • 28615364

Electronic International Standard Serial Number (EISSN)

  • 1538-7755

International Standard Serial Number (ISSN)

  • 1055-9965

Digital Object Identifier (DOI)

  • 10.1158/1055-9965.epi-17-0315

Language

  • eng