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

20 Citations (Scopus)

Abstract

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
Volume55
Issue number8
Early online date5 May 2018
DOIs
Publication statusPublished - Aug 2018

Keywords

  • 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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