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

Published version
Peer-reviewed

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Authors

Yang, Xin 
Leslie, Goska 
Gentry-Maharaj, Aleksandra 
Ryan, Andy 
Intermaggio, Maria 

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.

Description

Keywords

evaluation, ovarian cancer, polygenic risk scores, prospective cohort study, risk prediction, 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, Polymorphism, Single Nucleotide, Risk Assessment, Risk Factors

Journal Title

J Med Genet

Conference Name

Journal ISSN

0022-2593
1468-6244

Volume Title

55

Publisher

BMJ
Sponsorship
Cancer Research UK (20861)