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Functional Landscape of Common Variants Associated with Susceptibility to Epithelial Ovarian Cancer

  • Genetic Epidemiology (C Amos, Section Editor)
  • Published:
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Abstract

Purpose of the Review

To date, genome-wide association studies (GWASs) have identified 39 genomic loci associated with risk of epithelial ovarian cancer at genome-wide significance level (p ≤ 5 × 10−8) and 13 additional loci using less strict thresholds. Follow-up functional dissection of these loci to uncover the underlining mechanisms driving cancer susceptibility has been challenging.

Recent Findings

In a manner similar to how post-linkage studies led the characterization of then poorly understood cellular pathways, functional analysis of GWAS loci is revealing new mechanisms of ovarian cancer.

Summary

Here, we review recent methodological and conceptual progress relevant to the understanding of how common genetic variation influences the risk of epithelial ovarian cancer.

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Abbreviations

CCOC:

Clear cell ovarian carcinoma

DDR:

DNA damage response

ENOC:

Endometrioid ovarian carcinoma

EOC:

Epithelial ovarian cancer

eQTL:

Expression quantitative trait loci

GWAS:

Genome-wide association studies

HGSOC:

High-grade serous ovarian carcinoma

LD:

Linkage disequilibrium

LGSOC:

Low-grade serous ovarian carcinoma

MOC:

Mucinous ovarian carcinoma

MAF:

Minor allele frequency

OCAC:

Ovarian Cancer Association Consortium

PARP:

Poly ADP ribosyl polymerase

S/MAR:

Substrate/matrix attachment region

SNP:

Single nucleotide polymorphism

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Acknowledgments

We thank all the women who have donated their time and samples to make possible this work.

Funding

Funding for ovarian cancer research in the Monteiro Lab came from NIH awards U19 CA148112, R01 CA116167, and U54 CA163068 and from the Rivkin Center and the Moffitt Foundation. This study was funded in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brasil (CAPES)—Finance Code 001 and Fundação de Amparo à Pesquisa do Estado do Espírito Santo (FAPES).

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Authors and Affiliations

  1. Biotechnology/RENORBIO Program, Federal University of Espírito Santo, Vitória, ES, Brazil

    Paulo Cilas Morais Lyra Jr & Letícia B. Rangel

  2. Cancer Epidemiology Program, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, FL, USA

    Alvaro N. A. Monteiro

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  1. Paulo Cilas Morais Lyra Jr
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Correspondence to Alvaro N. A. Monteiro.

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Lyra, P.C.M., Rangel, L.B. & Monteiro, A.N.A. Functional Landscape of Common Variants Associated with Susceptibility to Epithelial Ovarian Cancer. Curr Epidemiol Rep 7, 49–57 (2020). https://doi.org/10.1007/s40471-020-00227-4

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