Approved Research

The role of clonal hematopoiesis of indeterminate potential in infection and cancer risk

Lay summary

As we age, the risk of serious illness increases dramatically. Cancer and infections are more common with age, in part because there is a failure of the aging immune system to properly respond to danger within tissues and effectively return the body to its normal state. Clonal hematopoiesis of indeterminate potential (CHIP) is a common immune system disorder that affects at least 10% of individuals aged 65 and older. Having CHIP predisposes individuals to an unhealthy aging trajectory, including increased risks of cardiovascular disease and premature death. However, it is not known whether CHIP also predisposes individuals to infections or to developing cancer.

In this project, we will study the associations between CHIP, infection risk and cancer risk in the UK Biobank over the next three years. We expect that CHIP will be associated with a higher risk for both overall, but we may see differences in the level of risk between different types of infections or different types of cancers. One important question we will address is whether CHIP is linked with an increased risk of COVID-19 infection, since findings in smaller cohorts have been conflicting. We will use newly available data measuring levels of proteins and other small molecules in the body to learn about possible mechanisms linking CHIP and the risk of infection or cancer, an approach that might serve as drug targets in the future. Since CHIP is so common, our findings could have important implications for the health of the aging population.

Scope extension, April 2024:

We aim to expand this inquiry to investigate the potential role of omega-3 fatty acids as a mediator of inflammation. Basic science research suggests a role for omega-3 fatty acids as precursors to pro-resolving lipid mediators. These important anti-inflammatory signaling molecules have been implicated in terminating adaptive inflammation so as to avoid maladaptive tissue damage. We propose to use UKB NMR metabolomics data to determine omega-3 status for participants and use this as the exposure in an observational study. The outcome variable will be hospitalization due to infection. We hypothesize that individuals with higher omega-3 levels will have a lower risk of this outcome, and will test this hypothesis using a Cox proportional hazards model.