Rare Genetic Mutation Linked to Lung Cancer Risk in Nonsmokers
A new study published in Science suggests that a rare inherited mutation in the EGFR gene may substantially increase lung cancer risk, including among people who have never smoked. Although smoking remains a leading cause of lung cancer, the CDC estimates that 10% to 20% of U.S. cases occur in people who never smoked.
Researchers co-led by Dr. Jaclyn LoPiccolo of Dana-Farber Cancer Institute analyzed genetic data from the 23andMe Research Institute. They found that carriers of the EGFR T790M mutation had a 25-fold higher risk of lung cancer than noncarriers, regardless of smoking history. Among nonsmokers, carriers had a 60-fold higher risk than nonsmokers without the mutation.
The variant is uncommon, affecting an estimated one in 15,000 Americans. Its prevalence is higher in Southern Appalachia, where about one in 2,000 people may carry it. Researchers believe the mutation may have entered the region through a person who arrived from England or Ireland more than two centuries ago.
The findings could inform future lung cancer screening policies. Current recommendations generally focus on older adults with substantial smoking histories and use low-dose CT scans. No evidence-based screening guidelines yet exist for younger nonsmokers who carry T790M.
Virginia resident Frank McKenna, a nonsmoker diagnosed with Stage IV lung cancer in 2016, learned that he carried the mutation and began targeted therapy. His daughter also carries T790M but currently lacks clear guidance on lung monitoring.
LoPiccolo’s INHERIT study is now examining inherited lung cancer risk alongside smoking history, family history, and environmental exposures. Researchers hope the results will help develop personalized screening schedules and detect cancers at earlier, more treatable stages. The Science study was funded by philanthropic organizations and a government grant; the Susan Wojcicki Foundation funded a separate genetics study that contributed data used in the researchers’ broader population-level risk analysis.