A rare genetic mutation in the EGFR T790M gene dramatically increases the risk of developing lung cancer, even in people who have never smoked, according to a new study published in Science. Researchers from Dana-Farber Cancer Institute and 23andMe analysed data from over 3.3 million people, finding that carriers of the mutation face approximately 62 times higher odds of lung cancer compared with never-smokers without the mutation. These findings could reshape lung cancer screening practices, which currently rely almost entirely on smoking history, by potentially incorporating genetic testing to identify at-risk individuals for personalised CT screening.

The mutation is remarkably rare, affecting roughly 1 in 15,000–16,000 people nationwide, although it is more prevalent in parts of Southern Appalachia where it may affect as many as 1 in 2,000 residents. Most US carriers share ancestry traced to British and Irish settlers who arrived in Southern Appalachia approximately 200–225 years ago. Researchers found no increased risk for the mutation across 17 other cancers studied, and noted that the risk compounds with smoking: a carrier who smokes faces the combined risk of both factors. The study has limitations, including relatively few carriers identified despite the large sample size, and reliance on 23andMe participants who may not represent the broader population.