Scientists have identified an inherited genetic mutation involving the EGFR gene that significantly elevates the risk of developing lung cancer, even among individuals who have never smoked. According to a study published on a Thursday in the journal Science, people who had never smoked and carried a specific mutation called EGFR T790M were 62 times more likely to develop lung cancer than non-smokers without the mutation.
Rare EGFR Mutation Drastically Raises Lung Cancer Risk
The EGFR gene normally helps control how cells grow, divide, and survive. By comparison, individuals who smoked but did not carry the mutation were four times likelier to develop lung cancer than non-smokers, meaning the mutation alone carried a higher risk of the disease. Among study participants who smoked and also carried the T790M mutation, the variant increased their cancer risk 11-fold compared with other smokers.
Dataset Analysis and Geographic Distribution
To conduct the research, investigators analyzed DNA and health data from more than 3.3 million people. The data was gathered from individuals who used 23andMe‘s at-home genetic testing kits and consented to have their personal information used for research, alongside two large public genetic databases known as All of Us and the UK Biobank.
Overall, the T790M mutation appeared in 1 out of every 15,850 people in the study of over 3.3 million individuals of European ancestry. When researchers examined where study participants were born, they discovered that the T790M mutation was much more prevalent among those born in the Southeast, particularly in the states of Alabama, Mississippi, and Tennessee. In those three states, the mutation showed up in 1 out of every 2,078 people who contributed data to 23andMe. Researchers also reviewed historical records to piece together how and when the mutation likely spread.
Expert Perspectives and Screening Trials
Chris Amos, a genetic epidemiologist at the Baylor College of Medicine who was not involved in the study, called the finding very important, noting that the prevalence of the T790M variant and its impact on lung cancer risk had previously been poorly understood. Amos argued that patients should be tested for this mutation if they have a family history of lung cancer in non-smokers or if their relatives are known to carry the mutation, adding that it influences both risk assessment and treatment decisions for those who already have cancer.
Dr. Stephen Chanock, director of the Division of Cancer Epidemiology and Genetics at the National Cancer Institute, who was also not involved in the research, noted that because the mutation is relatively rare, it likely does not account for a large percentage of overall lung cancer cases. However, Amos emphasized that the findings highlight the need to begin screening at an earlier age and irrespective of smoking status.
A clinical trial is currently underway to evaluate computed tomography (CT)-based lung cancer screening in people carrying the mutation, which will also help determine whether lung cancer risk increases with age in this population. Additionally, a study called INHERIT — led by LoPiccolo — includes people from across the country with inherited genetic risks for lung cancer, including the EGFR T790M mutation. As part of this effort, doctors collaborate with participants to review family history, smoking history, genetic profiles, and environmental exposures to develop personalized plans for regular screening using low-dose CT scans.
Related reading