Cancer, genetic susceptibility and risk of coronary artery disease: A prospective study.

OBJECTIVE

Cancer survivors have an increased risk of developing coronary artery disease (CAD). We introduce CAD polygenic risk scores (PRS) and examine associations with cancer status on CAD outcomes.

METHODS

From the UK Biobank, we identified cancer survivors and CAD outcomes among 464,193 CAD-free participants using linked cancer registries, hospitalizations, and death records. CAD-PRS was categorized as low (lowest tertile), intermediate (tertile 2), and high (highest tertile). Adjusted Cox models assessed the joint and interaction effects of cancer status and CAD-PRS on CAD outcomes.

RESULTS

Over the follow-up (median 11.7 years), 36,332 participants developed CAD. Compared to low CAD-PRS, the hazard ratios (HRs) and 95% confidence intervals (CIs) for CAD was 1.35 (1.31-1.38) for intermediate and 1.86 (1.81-1.91) for high CAD-PRS. The HR (95% CI) for CAD in cancer survivors was 1.16 (1.13-1.19) compared to those without cancer. In the joint effect analysis, compared to participants with low CAD-PRS and no cancer, the HRs (95% CIs) for CAD were 1.37 (1.32-1.41) and 1.90 (1.84-1.96) for intermediate and high CAD-PRS without cancer, respectively. For those with cancer, the HRs (95% CIs) were 1.26 (1.19-1.33), 1.59 (1.51-1.67), and 2.13 (2.03-2.23) for low, intermediate, and high CAD-PRS, respectively. A significant multiplicative interaction (HR: 0.94, 95% CI: 0.91-0.98) was observed between CAD-PRS and cancer status on CAD. Additionally, a significant additive interaction between cancer and high CAD-PRS was found for fatal CAD.

CONCLUSION

Cancer was associated with a higher risk of CAD and may further increase the risk of CAD related to genetic factors.