The EGFR T790M gene mutation, traced to British Isles settlers in Southern Appalachia 200-225 years ago, is found in about one in 15,000 Americans but one in 2,000 in Southern Appalachia, especially Tennessee and Alabama. It makes lung cancer 62 times more likely in never-smokers and 10 times more likely in smokers. Described as one of the most powerful cancer-risk mutations ever found, it was identified in a study by Dana-Farber Cancer Institute and 23andMe Research Institute using data from over 10 million participants, including 641 with the mutation.

Unlike other EGFR mutations that arise later in life and can affect multiple organs, T790M is inherited, not lethal in embryos, and associated only with lung cancer. Researchers hope the discovery enables early detection, treatment, and prevention. Caroline Blanchard, a nurse practitioner in New Orleans, learned she carries the gene after her aunt and grandmother developed lung cancer despite never smoking, highlighting its familial impact.