Cancer risk over an individual’s lifespan. An individual’s risk for CH and subsequent malignancies is shaped by the combined risk of germline genetic factors, comprised of high population frequency/low penetrance alleles (e.g., found in TERT) and low population frequency/high penetrance alleles (e.g., found in TP53 and ATM) with environmental exposures, such as tobacco use, highly processed foods, environmental toxins, and cancer-directed therapies, among others. Created in BioRender. Franco, S. (2024) https://BioRender.com/a12g213.