Summary
Most lung cancer is linked to smoking, but 10 to 20 percent of cases in the U.S. each year happen in people who’ve never smoked. A new study offers one of the clearest genetic explanations yet for some of those cases.
Researchers led by Dr. Jaclyn LoPiccolo at Dana-Farber Cancer Institute studied a rare inherited mutation in the EGFR gene called T790M. People who carry this mutation had a 25-fold higher risk of developing lung cancer compared to people without it, regardless of whether they smoked. Among nonsmokers specifically, the risk jumped even higher: nonsmokers with the mutation were 60 times more likely to develop lung cancer than nonsmokers without it.
This mutation is rare overall — only about 1 in 15,000 people in the U.S. carry it. But in one specific region, Southern Appalachia, the rate is far higher: about 1 in 2,000. Researchers believe a single carrier brought the mutation to the U.S. from England or Ireland more than 200 years ago, and it’s been passed down in that region ever since.
Until now, researchers knew this mutation was linked to lung cancer but didn’t have a large enough group of carriers to measure exactly how much it raised risk. This study used a massive genetic database from 23andMe’s Research Institute to finally get real numbers.
The findings raise a bigger question: should genetic testing become part of how we decide who gets screened for lung cancer? Right now, screening is only recommended for people with a heavy smoking history above a certain age — which means someone with this inherited mutation but no smoking history wouldn’t currently qualify.
Researchers point to BRCA testing for breast cancer as a possible model: identify carriers, then screen them more often and earlier, regardless of other risk factors. A new study called INHERIT is now testing exactly this approach — building personalized screening plans based on genetic risk, family history, and environmental exposures, rather than smoking history alone.
