Association Between Clonal Hematopoiesis, RCC, and Cardiovascular Disease

Valisha Shah, MS, computational biologist, BraunLab, Yale Medical School, Lank Center for Genitourinary Oncology, Dana-Farber Cancer Institute discusses the rationale behind a study investigating the relationship between clonal hematopoiesis, renal cell carcinoma (RCC), and cardiovascular diseases.

The inspiration for this study stemmed from the observed association between clonal hematopoiesis and RCC with cardiovascular diseases, Shah begins. However, the direct genetic relationship between these conditions, particularly with cardiovascular disorders and RCC, has not been comprehensively studied using genome-wide association studies (GWAS), she says.

The study aims to address this gap by examining common genetic pathways that may elucidate the shared predisposition to cardiovascular events in patients with RCC and clonal hematopoiesis. Shah explains that understanding these genetic links could provide insights into why patients with clonal hematopoiesis and RCC are more prone to developing cardiovascular diseases.

The investigation uses GWAS to identify genetic variants that are associated with both RCC and cardiovascular diseases. By exploring these genetic intersections, the research seeks to uncover potential mechanisms that drive the co-occurrence of these conditions. This approach could reveal novel targets for therapeutic intervention and inform the development of more personalized treatment strategies for patients, according to Shah.

Additionally, the study considers the implications of clonal hematopoiesis, a condition characterized by the presence of expanded clones of hematopoietic cells with acquired mutations, which has been linked to an increased risk of hematologic malignancies and cardiovascular diseases, Shah explains. The relationship between clonal hematopoiesis and RCC is less understood, prompting further investigation into how these expanded clones may contribute to the pathogenesis of RCC and its cardiovascular complications, Shah emphasizes.

Shah notes that amongst early findings, the lack of a genetic link implies that if there are genetic pathways perpetuating cardiovascular disease risk in patients with RCC, they are different from those associated with loss of Y chromosome disease. The clinical implications of identifying a pathway could be an impactful step in improving the understanding of the complex genetic relationship between these conditions, Shah continues. Additionally, identifying shared genetic pathways could lead to better risk stratification and treatment of patients with RCC and clonal hematopoiesis, ultimately reducing the incidence of cardiovascular events in this population, she explains.