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

doi:10.1136/jmedgenet-2018-105313

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

Applied Health Sciences

Cambridge University Hospitals NHS Foundation Trust
University of New South Wales
Samuel Oschin Comprehensive Cancer Institute
Queen Mary University of London
University College London

Research output: Contribution to journal › Article › peer-review

44 Citations (Scopus)

8 Downloads (Pure)

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 language	English
Pages (from-to)	546-554
Number of pages	9
Journal	Journal of Medical Genetics
Volume	55
Issue number	8
Early online date	5 May 2018
DOIs	https://doi.org/10.1136/jmedgenet-2018-105313
Publication status	Published - 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
(http://dx.doi.org/10.1136/
jmedgenet-2018-105313).

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

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

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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Yang_etal_CG_Evaluation_Of_Polygenic_VoR
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Cite this

Yang, X., Leslie, G., Gentry-Maharaj, A., Ryan, A., Intermaggio, M., Lee, A., Kalsi, J. K., Tyrer, J., Gaba, F., Manchanda, R., Pharoah, P. D. P., Gayther, S. A., Ramus, S. J., Jacobs, I., Menon, U., & Antoniou, A. C. (2018). Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study. Journal of Medical Genetics, 55(8), 546-554. https://doi.org/10.1136/jmedgenet-2018-105313

Yang, X, Leslie, G, Gentry-Maharaj, A, Ryan, A, Intermaggio, M, Lee, A, Kalsi, JK, Tyrer, J, Gaba, F, Manchanda, R, Pharoah, PDP, Gayther, SA, Ramus, SJ, Jacobs, I, Menon, U & Antoniou, AC 2018, 'Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study', Journal of Medical Genetics, vol. 55, no. 8, pp. 546-554. https://doi.org/10.1136/jmedgenet-2018-105313

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title = "Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study",

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{\texttimes}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{\texttimes}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.",

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",

author = "Xin Yang and Goska Leslie and Aleksandra Gentry-Maharaj and Andy Ryan and Maria Intermaggio and Andrew Lee and Kalsi, \{Jatinderpal K\} and Jonathan Tyrer and Faiza Gaba and Ranjit Manchanda and Pharoah, \{Paul D P\} and Gayther, \{Simon A\} and Ramus, \{Susan J\} and Ian Jacobs and Usha Menon and Antoniou, \{Antonis C\}",

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{\textquoteright}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 {\textcopyright} 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.",

year = "2018",

month = aug,

doi = "10.1136/jmedgenet-2018-105313",

language = "English",

volume = "55",

pages = "546--554",

journal = "Journal of Medical Genetics",

issn = "0022-2593",

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number = "8",

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TY - JOUR

T1 - Evaluation of polygenic risk scores for ovarian cancer risk prediction in a prospective cohort study

AU - Yang, Xin

AU - Leslie, Goska

AU - Gentry-Maharaj, Aleksandra

AU - Ryan, Andy

AU - Intermaggio, Maria

AU - Lee, Andrew

AU - Kalsi, Jatinderpal K

AU - Tyrer, Jonathan

AU - Gaba, Faiza

AU - Manchanda, Ranjit

AU - Pharoah, Paul D P

AU - Gayther, Simon A

AU - Ramus, Susan J

AU - Jacobs, Ian

AU - Menon, Usha

AU - Antoniou, Antonis C

N1 - 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.

PY - 2018/8

Y1 - 2018/8

N2 - 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.

AB - 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.

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KW - Aged

KW - Aged, 80 and over

KW - Biomarkers, Tumor

KW - Case-Control Studies

KW - Female

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Genotype

KW - Humans

KW - Middle Aged

KW - Multifactorial Inheritance

KW - Odds Ratio

KW - Ovarian Neoplasms/epidemiology

KW - Polymorphism, Single Nucleotide

KW - Risk Assessment

KW - Risk Factors

U2 - 10.1136/jmedgenet-2018-105313

DO - 10.1136/jmedgenet-2018-105313

M3 - Article

C2 - 29730597

SN - 0022-2593

VL - 55

SP - 546

EP - 554

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

IS - 8

ER -

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

Abstract

Bibliographical note

Data Availability Statement

UN SDGs

Keywords

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