Rare Inherited Gene Mutation Raises Lung Cancer Risk Up to 62-Fold in Nonsmokers, Study Finds

Researchers have identified a rare inherited mutation that sharply raises the odds of getting lung cancer, even in people who've never touched a cigarette. The study, published Thursday, September 17, 2026, in the journal Science, was co-led by Dr. Jaclyn LoPiccolo and Dr. Pasi Jänne of Dana-Farber Cancer Institute, working with the 23andMe Research Institute.

The mutation, called EGFR T790M, sits in a gene that normally controls how cells grow and divide. According to Live Science and Newsy Today, nonsmokers who carried the mutation were 62 times more likely to develop lung cancer than nonsmokers without it. By comparison, smokers without the mutation were only about four times likelier than nonsmokers to get the disease. Smokers who also carried T790M saw an 11-fold jump in risk compared to other smokers.

Dana-Farber's own summary of the study, echoed by TIME and News Medical, frames the numbers slightly differently: a 25-fold increased risk overall, and more than 60-fold among people who never smoked. The two framings aren't contradictory so much as different cuts of the same data, but the discrepancy underscores that this is a single large study, not multiple independent confirmations, funded in part through the Susan Wojcicki Foundation's Lung Cancer Genetics Study, according to Nadia Litterman, the foundation's executive director, speaking to TIME.

How They Found It

The research team analyzed genetic and health data from more than 3.3 million people, mostly drawn from 23andMe's research-consented database, according to Newsy Today, which also cited contributions from the UK Biobank and the National Institutes of Health's All of Us program. The mutation showed up in roughly 1 out of every 15,850 people studied, per Live Science.

That rarity comes with an important caveat: the core dataset was limited to people of European ancestry, Live Science reported. That means the risk estimates, however striking, may not translate cleanly to other populations, a limitation none of the six reports resolved.

A Southern Cluster

The mutation wasn't evenly spread. Newsy Today reported that people born in Alabama, Mississippi and Tennessee carried T790M at a rate of roughly 1 in 2,078, nearly eight times the national rate found in the study. TIME similarly reported a concentration in Southern Appalachia, at about 1 in 2,000, and said researchers believe a single carrier brought the mutation to the U.S. from England or Ireland more than 200 years ago. Researchers used historical records to trace that likely origin, according to Newsy Today.

T790M itself isn't new to science. It was first identified in 2005 in a European family with multiple lung cancer cases among nonsmokers, according to Dana-Farber's own release and News Medical. What changed is the scale: with 3.3 million genetic records to work with, researchers finally had enough carriers to calculate a population-level risk estimate, something Jänne said was previously impossible given how rare the variant is.

Why Experts Are Cautious, Not Alarmed

Chris Amos, a genetic epidemiologist at Baylor College of Medicine who wasn't involved in the study, called the finding "very important," telling Live Science that the prevalence and impact of T790M had been "poorly understood" until now. He argued patients with a family history of lung cancer among nonsmokers, or with relatives known to carry the mutation, should be tested, since it also affects treatment decisions for people already diagnosed.

But Dr. Stephen Chanock, director of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, offered a more measured take. Because the mutation is so rare, he told Live Science, it likely accounts for only a small slice of overall lung cancer cases. A 62-fold relative increase sounds enormous, but applied to a baseline risk that's already low for nonsmokers, and to a mutation carried by roughly 1 in 15,850 people nationally, the absolute number of cancers it explains is modest.

There's also a practical question the study doesn't answer: whether widescale genetic testing for a mutation this rare is worth the cost and anxiety it could generate, especially for people outside the Southern Appalachian cluster where prevalence is higher. Dr. LoPiccolo told Dana-Farber that current lung cancer screening is driven "almost entirely by smoking history," and that her findings raise the possibility of screening based on inherited risk instead, or in addition.

That possibility is already being tested. According to News Medical, additional data supporting the study came from the ongoing INHERIT Study, led by LoPiccolo and Jänne in partnership with GO2 for Lung Cancer and the Addario Lung Cancer Medical Institute, registered under NCT05587439. Newsy Today reported a clinical trial is underway evaluating CT-based screening specifically for T790M carriers. Whether that screening actually catches cancers earlier, and whether it justifies expanding genetic testing beyond people with a strong family history, remains an open question the trial is designed to answer.