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Original article
Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study
  1. Xin Yang1,
  2. Goska Leslie1,
  3. Aleksandra Gentry-Maharaj2,
  4. Andy Ryan2,
  5. Maria Intermaggio3,
  6. Andrew Lee1,
  7. Jatinderpal K Kalsi2,
  8. Jonathan Tyrer4,
  9. Faiza Gaba5,
  10. Ranjit Manchanda2,5,6,
  11. Paul D P Pharoah1,4,
  12. Simon A Gayther7,8,
  13. Susan J Ramus3,9,
  14. Ian Jacobs2,10,11,
  15. Usha Menon2,
  16. Antonis C Antoniou1
  1. 1 Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK
  2. 2 Department of Women’s Cancer, Institute for Women’s Health, University College London, London, UK
  3. 3 School of Women’s and Children’s Health, University of New South Wales, Sydney, New South Wales, Australia
  4. 4 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
  5. 5 Centre for Experimental Cancer Medicine, Barts Cancer Institute, Queen Mary University of London, London, UK
  6. 6 Department of Gynaecological Oncology, Barts Health NHS Trust, Royal London Hospital, London, UK
  7. 7 Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
  8. 8 Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California, USA
  9. 9 The Kinghorn Cancer Centre, Garvan Institute of Medical Research, Sydney, New South Wales, Australia
  10. 10 University of New South Wales, Sydney, New South Wales, Australia
  11. 11 University of Manchester, Manchester, UK
  1. Correspondence to Prof Antonis C Antoniou, Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK; aca20{at}


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.

  • polygenic risk scores
  • ovarian cancer
  • prospective cohort study
  • risk prediction
  • evaluation

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  • Contributors XY and ACA performed the data analysis and drafted the manuscript. ACA, AG-M, UM and IJ conceived and designed the study. GL, AG-M and AR were involved in the data processing and data management. MI, SAG and SJR performed the genotyping. AG-M, AR, JKK, IJ and UM are coordinating the UKCTOCS study (PIs: IJ, UM). AL, JT, FG, RM and PDPP contributed to the analytical design and/or interpretation of data. All authors critically reviewed the manuscript.

  • Funding 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.

  • Disclaimer The funding source or the sponsor had no role in data collection, data analysis, data interpretation or writing of the report. The researchers are independent from the funders.

  • Competing interests UM and IJ have a financial interest through Abcodia Ltd in the third party exploitation of the trial biobank.

  • Patient consent Not required.

  • Ethics approval UKCTOCS was approved by the UK North West Multicentre Research Ethics Committees (North West MREC 00/8/34) on 21 June 2000 with site-specific approval from the local regional ethics committees and the Caldicott guardians (data controllers) of the primary care trusts. The SNP protocol was approved by NRES Committee North West – Liverpool Central (14/NW1026) in June 2014.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement Requests for access to data should be addressed for consideration to the UKCTOCS PI UM.

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