Journal article
Polygenic risk of coronary artery disease for long-term survivors of breast cancer
JNCI : Journal of the National Cancer Institute, Vol.117(10), pp.2073-2081
10/01/2025
DOI: 10.1093/jnci/djaf189
PMCID: PMC12505140
PMID: 40665521
Abstract
Cardiovascular disease is a leading cause of death for long-term breast cancer survivors. We evaluated whether a polygenic risk score for coronary artery disease (CAD-PRS) was associated with the risk of incident CAD for survivors of unilateral or contralateral breast cancer.
The study included 1,307 women with breast cancer first diagnosed at age <55 years who participated in the WECARE Follow-up Study. The CAD-PRS was based on a PRS developed and validated in a separate population. We modelled the association between incident CAD and the CAD-PRS, adjusting for age, CAD risk factors, first (and second) breast cancer treatment, study recruitment phase, and genetic population stratification. We also explored whether the risk of CAD depended on interactions between the CAD-PRS and cardiotoxic cancer treatment.
There were 65 incident CAD diagnoses reported at a median of 16 years after breast cancer diagnosis. Participants with CAD-PRS≥median had a 2.48-times increased risk of CAD (95%CI = 1.44-4.29) relative to participants with CAD-PRS<median. Anthracycline-based chemotherapy was associated with increased CAD risk (HR = 2.04, 95%CI = 1.04-3.98), and the association was not modified by the CAD-PRS. The association between incident CAD and left-sided RT was increased for those with CAD-PRS≥median (HR = 2.90, 95% CI = 1.26-6.68), but not for those with CAD-PRS<median (HR = 0.96, 95% CI 0.32-2.88). There was evidence of super-additive interaction between the CAD-PRS and left-sided RT (relative excess risk due to interaction = 2.06, 95% CI 0.05-4.06).
A genome-wide CAD-PRS was associated with non-fatal CAD risk for long-term breast cancer survivors, providing potential utility for personalized cardiovascular care, particularly after RT.
Details
- Title: Subtitle
- Polygenic risk of coronary artery disease for long-term survivors of breast cancer
- Creators
- Gordon P Watt - Memorial Sloan Kettering Cancer CenterAnne S Reiner - Memorial Sloan Kettering Cancer CenterXiang Shu - Memorial Sloan Kettering Cancer CenterKathleen E Malone - Fred Hutch Cancer CenterJulia A Knight - Lunenfeld-Tanenbaum Research InstituteEsther M John - Stanford UniversityEric J Chow - Fred Hutch Cancer CenterCharles F Lynch - University of IowaLene Mellemkjær - Danish Cancer SocietyMeghan Woods - Memorial Sloan Kettering Cancer CenterXiaolin Liang - Memorial Sloan Kettering Cancer CenterAnh Phong Tran - Memorial Sloan Kettering Cancer CenterJung Hun Oh - Memorial Sloan Kettering Cancer CenterAndriy Derkach - Memorial Sloan Kettering Cancer CenterJonine L Bernstein - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- JNCI : Journal of the National Cancer Institute, Vol.117(10), pp.2073-2081
- DOI
- 10.1093/jnci/djaf189
- PMID
- 40665521
- PMCID
- PMC12505140
- NLM abbreviation
- J Natl Cancer Inst
- ISSN
- 0027-8874
- eISSN
- 1460-2105
- Publisher
- OXFORD UNIV PRESS INC
- Grant note
- United States National Cancer InstituteWECARE Study Data collection site Principal Investigators
The WECARE Study team would like to thank the participants of this study who made this research possible. The authors would also like to thank the WECARE Study Data collection site Principal Investigators and their research staff that worked to obtain these data. Finally, the authors would like to thank Prof. Dr Flora van Leeuwen and Dr Michael Schaapveld for their advice on this study.
- Language
- English
- Electronic publication date
- 07/16/2025
- Date published
- 10/01/2025
- Academic Unit
- Epidemiology
- Record Identifier
- 9984848000402771
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