Scientists have discovered a rare inherited mutation in the EGFR gene that significantly raises the risk of lung cancer, even in people who have never smoked. A study published in the journal Science found that individuals who never smoked and carried the EGFR T790M mutation were 62 times more likely to develop lung cancer than nonsmokers without the mutation. In contrast, smokers without the mutation had a fourfold increased risk compared to nonsmokers, while smokers with the mutation faced an 11-fold higher risk than other smokers. This highlights the mutation’s strong impact on cancer risk, independent of smoking. The study analyzed data from over 3 million people of European ancestry and found the T790M mutation in about 1 in every 15,850 individuals. Importantly, the mutation was not associated with other types of cancer or noncancerous lung conditions. Researchers note that while the mutation is rare in the general population, it could still play a role in a small fraction of lung cancer cases. The study relied heavily on genetic data from 23andMe, a company that provides at-home DNA testing, which had a much larger sample of people with the mutation than other databases. The T790M mutation was more common in people born in the Southeastern United States, especially in Alabama, Mississippi, and Tennessee, where it occurred in about 1 in every 2,078 individuals. Researchers believe the mutation was introduced to the U.S. by settlers from the British Isles in the early 1700s and became more common in southern Appalachia due to historical isolation and repeated transmission within families. This geographic concentration may partly explain the region’s higher lung cancer rates, though the area also has higher smoking rates than the national average. The study found that individuals with the T790M mutation tend to develop lung cancer about five years earlier than those without the mutation. This suggests that people with the mutation may benefit from earlier screening, regardless of whether they smoke. A clinical trial is currently testing CT-based lung cancer screening for those with the mutation, and more research is needed to understand how the mutation increases cancer risk and whether environmental factors interact with it. Experts also plan to investigate other rare genetic mutations that may contribute to inherited lung cancer risk, as the T790M mutation is just one of many possible genetic factors.