Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.
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Authors
Kaptoge, Stephen
Dennis, Joe
Shah, Mitul
Tyrer, Jonathan
Inouye, Michael
Easton, Douglas F
Pharoah, Paul D P
Publication Date
2021-09-30Journal Title
Breast cancer research : BCR
ISSN
1465-5411
Volume
23
Issue
1
Language
eng
Type
Article
This Version
VoR
Metadata
Show full item recordCitation
Liou, L., Kaptoge, S., Dennis, J., Shah, M., Tyrer, J., Inouye, M., Easton, D. F., & et al. (2021). Genomic risk prediction of coronary artery disease in women with breast cancer: a prospective cohort study.. Breast cancer research : BCR, 23 (1) https://doi.org/10.1186/s13058-021-01465-0
Description
Funder: Wellcome Trust
Abstract
<h4>Background</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
Keywords
Breast cancer, Cardiovascular disease, coronary artery disease, Coronary Heart Disease, Search, Polygenic Risk Score
Sponsorship
British Heart Foundation (RG/13/13/30194, RG/18/13/33946)
NIHR Newcastle Biomedical Research Centre (C490/A16561)
Identifiers
PMC8482562, 34593009
External DOI: https://doi.org/10.1186/s13058-021-01465-0
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330180
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