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Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.

Published version
Peer-reviewed

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Authors

Kaptoge, Stephen 
Dennis, Joe 
Shah, Mitul 
Tyrer, Jonathan 

Abstract

BACKGROUND: Advancements in cancer therapeutics have resulted in increases in cancer-related survival; however, there is a growing clinical dilemma. The current balancing of survival benefits and future cardiotoxic harms of oncotherapies has resulted in an increased burden of cardiovascular disease in breast cancer survivors. Risk stratification may help address this clinical dilemma. This study is the first to assess the association between a coronary artery disease-specific polygenic risk score and incident coronary artery events in female breast cancer survivors. METHODS: We utilized the Studies in Epidemiology and Research in Cancer Heredity prospective cohort involving 12,413 women with breast cancer with genotype information and without a baseline history of cardiovascular disease. Cause-specific hazard ratios for association of the polygenic risk score and incident coronary artery disease (CAD) were obtained using left-truncated Cox regression adjusting for age, genotype array, conventional risk factors such as smoking and body mass index, as well as other sociodemographic, lifestyle, and medical variables. RESULTS: Over a median follow-up of 10.3 years (IQR: 16.8) years, 750 incident fatal or non-fatal coronary artery events were recorded. A 1 standard deviation higher polygenic risk score was associated with an adjusted hazard ratio of 1.33 (95% CI 1.20, 1.47) for incident CAD. CONCLUSIONS: This study provides evidence that a coronary artery disease-specific polygenic risk score can risk-stratify breast cancer survivors independently of other established cardiovascular risk factors.

Description

Keywords

Breast cancer, Cardiovascular disease, Coronary artery disease, Coronary heart disease, Polygenic risk score, SEARCH, Breast Neoplasms, Cancer Survivors, Coronary Artery Disease, Female, Genome-Wide Association Study, Genomics, Genotype, Humans, Incidence, Middle Aged, Multifactorial Inheritance, Proportional Hazards Models, Prospective Studies, Risk Factors, United Kingdom

Journal Title

Breast Cancer Res

Conference Name

Journal ISSN

1465-5411
1465-542X

Volume Title

23

Publisher

Springer Science and Business Media LLC
Sponsorship
Cancer Research Uk (None)
Medical Research Council (MR/L003120/1)
British Heart Foundation (None)
British Heart Foundation (RG/18/13/33946)
National Institute for Health and Care Research (IS-BRC-1215-20014)
British Heart Foundation (CH/12/2/29428)