# Population-enriched innate immune variants may identify candidate gene targets at the intersection of cancer and cardio-metabolic disease

## TL;DR

This paper explores how genetic differences in the immune system may explain why certain populations have higher rates of cancer and heart-related diseases.

## Contribution

The paper proposes that population-specific innate immune gene variants could be key to understanding and addressing health disparities in cancer and cardio-metabolic diseases.

## Key findings

- Population-specific genetic variations in innate immune genes may contribute to disparities in cancer and cardio-metabolic diseases.
- Innate immune genes may serve as novel targets for precision-based treatments of these diseases.
- Genetic markers linked to geographic ancestry may influence immune responses and disease susceptibility.

## Abstract

Both cancer and cardio-metabolic disease disparities exist among specific populations in the US. For example, African Americans experience the highest rates of breast and prostate cancer mortality and the highest incidence of obesity. Native and Hispanic Americans experience the highest rates of liver cancer mortality. At the same time, Pacific Islanders have the highest death rate attributed to type 2 diabetes (T2D), and Asian Americans experience the highest incidence of non-alcoholic fatty liver disease (NAFLD) and cancers induced by infectious agents. Notably, the pathologic progression of both cancer and cardio-metabolic diseases involves innate immunity and mechanisms of inflammation. Innate immunity in individuals is established through genetic inheritance and external stimuli to respond to environmental threats and stresses such as pathogen exposure. Further, individual genomes contain characteristic genetic markers associated with one or more geographic ancestries (ethnic groups), including protective innate immune genetic programming optimized for survival in their corresponding ancestral environment(s). This perspective explores evidence related to our working hypothesis that genetic variations in innate immune genes, particularly those that are commonly found but unevenly distributed between populations, are associated with disparities between populations in both cancer and cardio-metabolic diseases. Identifying conventional and unconventional innate immune genes that fit this profile may provide critical insights into the underlying mechanisms that connect these two families of complex diseases and offer novel targets for precision-based treatment of cancer and/or cardio-metabolic disease.