Researchers have found that an unusually rare inherited mutation in the EGFR gene, known as EGFR T790M, dramatically increases the risk of lung cancer, including among people who have never smoked. The mutation makes lung cancer about 62 times more likely in lifelong nonsmokers and 10 times more likely in smokers, making it one of the strongest cancer-risk mutations identified to date. The mutation appears to have originated roughly 200 to 225 years ago in one or more people from the British Isles. Their descendants carried it to the United States, where it is now concentrated, particularly in Southern Appalachia and states such as Tennessee and Alabama. Researchers estimate that approximately one in 15,000 people in the United States carries the mutation, compared with about one in 2,000 people in Southern Appalachia. The findings, published in Science, were made possible by analyzing genetic and health information from 23andMe Research. The database included genetic data and lung-cancer information from about 3.37 million participants, 641 of whom carried the mutation. This large sample allowed scientists to estimate the mutation’s cancer risk and determine that it is specifically associated with lung cancer rather than a broad range of cancers. Unlike many EGFR mutations that develop randomly later in life, EGFR T790M is present from birth and does not prevent normal development. Researchers hope the discovery will lead to earlier detection, improved monitoring, and possibly preventive treatments for carriers. It also raises questions about whether people with the mutation should receive CT scans earlier or more frequently than current screening guidelines recommend, which generally focus on older smokers and former smokers.

The Rising Mystery of Lung Cancer in Non-Smokers: What’s Behind This Growing Threat? Lung cancer is often linked in our