Abstract
BackgroundGenome-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.MethodsWe 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.ResultsThe 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.ConclusionPRSs 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.
Funder
Special Trustees of UCLH
the Eve Appeal
Cancer Research UK
the Medical Research Council
Special Trustees of Bart’s and the London
the Department of Health
Subject
Genetics (clinical),Genetics
Reference23 articles.
1. Cancer Research UK. Let’s beat cancer sooner. https://www.cancerresearchuk.org/ (acessed 18 Jan 2018).
2. Ten-Year Relative Survival for Epithelial Ovarian Cancer
3. A risk prediction algorithm for ovarian cancer incorporatingBRCA1, BRCA2, common alleles and other familial effects
4. Bahcall O . Common variation and heritability estimates for breast, ovarian and prostate cancers. http://www.nature.com/icogs/primer/common-variation-and-heritability-estimates-for-breast-ovarian-and-prostate-cancers/ (acessed 18 Jan 2018).
5. Identification of six new susceptibility loci for invasive epithelial ovarian cancer
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