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
Funder: Wellcome Trust
Keywords
Breast cancer, Cardiovascular disease, coronary artery disease, Coronary Heart Disease, Search, Polygenic Risk Score
Journal Title
Breast cancer research : BCR
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Journal ISSN
1465-5411
Volume Title
23
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Sponsorship
British Heart Foundation (RG/13/13/30194, RG/18/13/33946)
NIHR Newcastle Biomedical Research Centre (C490/A16561)
NIHR Newcastle Biomedical Research Centre (C490/A16561)