A CAD polygenic risk score at or above the median was associated with a 2.48-times increased risk of incident CAD in long-term breast cancer survivors (95% CI 1.44-4.29).
Cohort (n=1,307)
Does a high polygenic risk score for coronary artery disease predict incident CAD in long-term survivors of breast cancer?
A genome-wide polygenic risk score for CAD identifies long-term breast cancer survivors at increased risk for incident CAD, particularly those who received left-sided radiation therapy.
Hazard Ratio: 2.48 (95% CI 1.44–4.29)
BACKGROUND: 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. METHODS: The study included 1307 women with breast cancer first diagnosed at younger than 55 years of age who participated in the Women's Environmental Cancer and Radiation Epidemiology Follow-up Study. The CAD-PRS was based on a PRS developed and validated in a separate population. We modeled 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. RESULTS: There were 66 incident CAD diagnoses reported at a median of 16 years after breast cancer diagnosis. Participants with CAD-PRS at or above the median had a 2.48-times increased risk of CAD (95% confidence interval CI = 1.44 to 4.29) relative to participants with CAD-PRS below the median. Anthracycline-based chemotherapy was associated with increased CAD risk (hazard ratio HR = 2.04, 95% CI = 1.04 to 3.98), and the association was not modified by the CAD-PRS. The association between incident CAD and left-sided radiation therapy (RT) was increased for those with CAD-PRS at or above the median (HR = 2.90, 95% CI = 1.26 to 6.68) but not for those with CAD-PRS below the median (HR = 0.96, 95% CI = 0.32 to 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 to 4.06). CONCLUSION: A genome-wide CAD-PRS was associated with nonfatal CAD risk for long-term breast cancer survivors, providing potential utility for personalized cardiovascular care, particularly after RT.
Watt et al. (Mon,) conducted a cohort in Breast cancer (n=1,307). Polygenic risk score for coronary artery disease (CAD-PRS) ≥ median vs. CAD-PRS < median was evaluated on Incident CAD (HR 2.48, 95% CI 1.44-4.29). A CAD polygenic risk score at or above the median was associated with a 2.48-times increased risk of incident CAD in long-term breast cancer survivors (95% CI 1.44-4.29).
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