Key Takeaways:
- A rare EGFR mutation increases lung cancer risk 62-fold in non-smokers, a study shows.
- Found in one in 15,000 Americans, the inherited trait is concentrated in Southern Appalachia.
- Researchers hope the finding expands CT lung screening guidelines beyond traditional smoking histories.
Researchers have identified a rare inherited EGFR mutation that sharply raises lung cancer risk in nonsmokers, potentially changing how doctors assess screening needs.
Rare Mutation Shows Strong Cancer Link
The study, published Thursday in Science, found that people carrying the EGFR T790M mutation faced about 25 times the risk of lung cancer compared with people without it. Among people who had never smoked, carriers faced about 62 times the lung cancer risk in nonsmokers.
Researchers analyzed genetic and health data from more than 3.3 million participants in the 23andMe Research Institute database. The mutation is extremely rare, occurring in about one in 15,000 people in the United States, according to the study.
Jaclyn LoPiccolo, an attending physician and lung cancer researcher at Dana-Farber Cancer Institute, co-led the study. She said the findings could eventually shift lung cancer screening from relying mainly on smoking history to also considering inherited genetic risk.
“Today, lung cancer screening is driven almost entirely by smoking history,” LoPiccolo said in a Dana-Farber statement. She said future screening could include personalized CT scans for people who carry the mutation if further research confirms the benefit.
Researchers Trace Mutation Through U.S. Population
Scientists first identified the inherited EGFR T790M mutation in a European family in 2005 after several family members developed lung cancer. Its rarity previously made it difficult to measure how strongly the mutation affects cancer risk.
The new analysis found that carriers are concentrated in parts of Southern Appalachia, particularly Tennessee and Alabama. Researchers say the mutation likely arrived in the United States with British and Irish settlers more than 200 years ago and became more common in relatively isolated populations.
Pasi Jänne, a lung cancer specialist at Dana-Farber and co-senior author of the study, said the large database allowed researchers to measure the mutation’s effect more precisely.
“For years we’ve known that some families inherit a markedly increased risk of lung cancer,” Jänne said. “By studying more than three million people, we were able to demonstrate just how strongly this inherited mutation is associated with lung cancer.”
Study Could Shape Future Screening
The findings could affect how doctors identify people who may face lung cncer risk in nonsmokers and may need closer monitoring. Nadia Litterman, executive director of the Susan Wojcicki Foundation, said genetic risk information could eventually help guide screening decisions. The foundation funded a lung cancer genetics study that supplied data used in the analysis, but did not fund the new study itself.
Lung cancer survivor Frank McKenna, who never smoked, learned he carried the mutation after being diagnosed with Stage IV lung cancer in 2016. His daughter also carries T790M, but there are currently no evidence-based recommendations for how she should monitor her lungs.
Researchers are continuing the INHERIT study to examine inherited lung cancer risks and better understand lung cancer risk in nonsmokers, while developing personalized approaches to low-dose CT screening.
