Cardiovascular disease (CVD) and cancer are leading causes of death and comprise heterogeneous clinical phenotypes with diverse risk factors, disease courses, and treatments. Increasing evidence indicates that shared pathophysiological mechanisms, particularly chronic inflammation and immune dysregulation, contribute to cardiovascular manifestations such as myocarditis and heart failure, as well as to cancer development and resistance to immunotherapy. These mechanisms establish a bidirectional link between CVD and cancer, underlying cancer- and cancer therapy-associated cardiovascular toxicity and the impact of pre-existing CVD on cancer initiation and progression.
While the genetic landscape of CVD and cancer, including pathogenic and likely pathogenic variants, is increasingly characterised, drivers of adverse outcomes in specific disease entities such as cardio-oncologic syndromes and inflammatory CVD remain poorly understood. Experimental data from murine models of viral myocarditis suggest that mitochondrial gene dysfunction may represent a key driver of immune cell infiltration and progressive myocardial injury. However, to date, no large-scale genome-wide association study has linked viral myocarditis with inflammatory cardiomyopathy. This project aims to elucidate the intersection of CVD and cancer by leveraging clinical, genetic, imaging, and molecular data from the UK Biobank. By integrating large-scale genetic data with detailed clinical and imaging phenotypes, the project will advance understanding of genetic and clinical determinants across inflammation-driven conditions, including heart failure, myocarditis, concomitant or sequential CVD and cancer, and cancer therapy-related cardiovascular toxicity. Specific objectives include identifying genetic loci associated with cardiotoxicity, characterising reverse cardio-oncology, investigating inflammation-related mitochondrial dysfunction, and defining systemic manifestations of inflammatory heart disease.
