Cancer risk is not written in the genome or the environment alone. It emerges from the interaction between the two. At Fox Chase Cancer Center, Khadijah A. Mitchell, PhD, MS, is working to make that interaction measurable.
Mitchell’s research examines how lung cancer risk is shaped by the interaction between environmental exposures - including radon, tobacco smoke, air pollution and other place-based factors - and genetic ancestry, inherited susceptibility, DNA damage and repair, and molecular response.
“We have become extraordinarily good at measuring the genome,” Mitchell said. “But we still know much less about the environmental exposures that genome has experienced over a lifetime and why the same exposure may lead to cancer in one person but not another.”
Mitchell came to exposomics through cancer genetics. Her earlier genomic, transcriptomic, and proteomic studies examined biological differences associated with lung cancer disparities, including homologous recombination deficiency.
Her current program asks the next question: What environmental context is the genome responding to?
Using genomics, transcriptomics, metabolomics, functional studies of DNA damage and repair, and population-scale data, Mitchell is investigating how exposure and biological susceptibility intersect.
One component uses large-scale resources including the NIH All of Us Research Program to integrate genomic, environmental, behavioral, and place-based data in studies of lung cancer susceptibility. Complementary molecular and functional studies are examining biological mechanisms that may underlie those population-level patterns.
Radon is currently the program’s most developed exposure-specific focus. Mitchell leads a Pennsylvania Department of Health-supported radon health equity project focused on education, testing, and risk reduction in Southeastern Pennsylvania, particularly in environmental justice communities. Her work is particularly relevant in Pennsylvania, where approximately 40% of homes tested have radon levels above the EPA action guideline.
Mitchell is also a U.S. investigator and co-applicant on a five-year Canadian Institutes of Health Research/Canadian Cancer Society team grant led by Aaron Goodarzi, PhD, examining lung cancer risk from combined exposure to radon and wildfire smoke. Her role focuses on how genetics and DNA-repair capacity modify susceptibility to those environmental pollutants.
The work is currently in an active discovery and integration phase. Mitchell emphasizes that there is not yet a validated exposure biomarker or exposome-based screening test. The near-term goal is to determine whether combinations of environmental exposure, inherited susceptibility, and DNA-repair capacity can reproducibly explain differences in lung cancer risk and biological response.
These questions are particularly relevant for people whose risk is not fully captured by traditional smoking-based models, including people who have never smoked and those who develop lung cancer at younger ages.
Longer term, that evidence could support risk models that extend beyond age and smoking history to incorporate environmental exposure and biological susceptibility - bringing the principles of precision medicine into cancer prevention.
That translational pathway extends beyond the laboratory. Mitchell founded and chairs the Radon Health Equity Workgroup and works with public-health and community partners on testing, mitigation, education, and environmental policy. Her Fox Chase collaborations are also expanding across Cancer Prevention and Control, clinical programs, data science, and Community Outreach and Engagement.
For Fox Chase, cancer exposomics represents an emerging institutional strength: connecting fundamental cancer biology with population science, environmental health, community engagement, and policy. The goal is not to move away from the genome. It is to understand it more completely - and ultimately to make precision oncology begin before cancer develops.
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