On Sept. 17, 2026, investigators at Dana-Farber Cancer Institute and 23andMe Research Institute report that a rare inherited mutation in the Epidermal Growth Factor Receptor (EGFR) gene is associated with a 25-fold increased risk of lung cancer. The findings included de-identified, aggregated genetic data from more than 3.3 million 23andMe research-consented participants.

Among people who never smoked, carriers of the mutation were more than 60 times as likely to develop lung cancer as people without it. Researchers identified EGFR T790M as one of the strongest inherited risk factors for lung cancer discovered to date. This could have important implications for genetic testing and future lung cancer screening strategies for people who carry the mutation. The findings were published in Science.

Although most lung cancers are associated with tobacco use or exposure, the proportion diagnosed in people who have never smoked has been rising. Yet the genetic factors underlying these cancers, particularly the role of inherited risk, aren’t well understood.

In 2005, researchers identified a rare inherited mutation called EGFR T790M in a European family with multiple cases of lung cancer. Since then, the mutation has been reported in other families with unusually high rates of the disease.

“For years we’ve known that some families inherit a markedly increased risk of lung cancer, but because this variant is so rare, we’ve never been able to accurately measure that risk,” said co-senior author Pasi A. Jänne, M.D., Ph.D., Senior Vice President for Translational Research and a lung cancer specialist at Dana-Farber. “By studying more than three million people, we were able to demonstrate just how strongly this inherited mutation is associated with lung cancer.”

Comparing people with lung cancer to those without the disease, the researchers examined whether EGFR T790M was more common among those who had developed lung cancer. They also analyzed people who had never smoked separately to determine whether the association persisted in the absence of tobacco use. Additional data supporting the association came from participants in the INHERIT Study (NCT05587439), led at Dana-Farber by Drs. LoPiccolo and Jänne, in partnership with GO2 for Lung Cancer (GO2) and the Addario Lung Cancer Medical Institute (ALCMI).

Among people who smoked, carriers of the mutation were about 10 times as likely to develop lung cancer as noncarriers. Among people who never smoked, carriers were more than 60 times as likely to develop lung cancer. This relative risk does not mean smoking is protective, the researchers explained. Because smoking already greatly increases lung cancer risk, the mutation’s effect appears smaller by comparison. The mutation was not linked to any of 17 other common cancers studied, suggesting that its effects may be largely limited to lung cancer.