Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study

Xin Yang, Goska Leslie, Aleksandra Gentry-Maharaj, Andy Ryan, Maria Intermaggio, Andrew Lee, Jatinderpal K Kalsi, Jonathan Tyrer, Faiza Gaba, Ranjit Manchanda, Paul D P Pharoah, Simon A Gayther, Susan J Ramus, Ian Jacobs, Usha Menon, Antonis C Antoniou* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)
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BACKGROUND: Genome-wide association studies have identified >30 common SNPs associated with epithelial ovarian cancer (EOC). We evaluated the combined effects of EOC susceptibility SNPs on predicting EOC risk in an independent prospective cohort study.

METHODS: We genotyped ovarian cancer susceptibility single nucleotide polymorphisms (SNPs) in a nested case-control study (750 cases and 1428 controls) from the UK Collaborative Trial of Ovarian Cancer Screening trial. Polygenic risk scores (PRSs) were constructed and their associations with EOC risk were evaluated using logistic regression. The absolute risk of developing ovarian cancer by PRS percentiles was calculated.

RESULTS: The association between serous PRS and serous EOC (OR 1.43, 95% CI 1.29 to 1.58, p=1.3×10-11) was stronger than the association between overall PRS and overall EOC risk (OR 1.32, 95% CI 1.21 to 1.45, p=5.4×10-10). Women in the top fifth percentile of the PRS had a 3.4-fold increased EOC risk compared with women in the bottom 5% of the PRS, with the absolute EOC risk by age 80 being 2.9% and 0.9%, respectively, for the two groups of women in the population.

CONCLUSION: PRSs can be used to predict future risk of developing ovarian cancer for women in the general population. Incorporation of PRSs into risk prediction models for EOC could inform clinical decision-making and health management.

Original languageEnglish
Pages (from-to)546-554
Number of pages9
JournalJournal of Medical Genetics
Issue number8
Early online date5 May 2018
Publication statusPublished - Aug 2018

Bibliographical note

This work has been supported by grants from Cancer Research UK
(C12292/A20861, C1005/A12677) including the PROMISE research programme
and the Eve Appeal. UKCTOCS was core funded by the Medical Research Council,
Cancer Research UK (C1005/A12677), and the Department of Health with additional
support from the Eve Appeal, Special Trustees of Bart’s and the London, and Special
Trustees of UCLH and supported by researchers at the National Institute for Health
Research University College London Hospitals Biomedical Research Centre

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Data Availability Statement

Additional material is
published online only. To view
please visit the journal online

Requests for access to data should be addressed for
consideration to the UKCTOCS PI UM.


  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor
  • Case-Control Studies
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Middle Aged
  • Multifactorial Inheritance
  • Odds Ratio
  • Ovarian Neoplasms/epidemiology
  • Polymorphism, Single Nucleotide
  • Risk Assessment
  • Risk Factors


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