A landmark study published in Science has confirmed that a single inherited genetic mutation — EGFR T790M — dramatically elevates lung cancer risk, particularly in people who have never smoked. Researchers from Dana-Farber Cancer Institute partnered with 23andMe to analyze data from more than 3.3 million individuals, making it one of the largest genetic studies of its kind.

The mutation, historically known as a resistance variant found in tumors, was found to exist in normal (germline) DNA and confer an outsized cancer risk. Crucially, the variant showed no association with any of the 17 other cancers studied — making it uniquely and specifically tied to lung cancer.

By the Numbers:

• 25x increased lung cancer risk overall for EGFR T790M carriers
• 60x increased risk among never-smokers specifically
• ~7x risk increase from smoking alone — roughly 3–4 times lower than this single mutation
• 1 in 15,850 individuals carry the variant overall; 1 in 2,078 in parts of the Southern Appalachian region
• 20,000–40,000 never-smokers are diagnosed with lung cancer annually in the U.S.

Why it matters: Current U.S. lung cancer screening guidelines are built around smoking history, potentially missing up to 65% of patients who develop the disease. Identifying high-risk genetic carriers like EGFR T790M could open the door to expanded, genetics-based screening programs — potentially catching cancers earlier and saving lives.