A rare genetic mutation might significantly raise the risk of lung cancer for individuals, even if they’ve never smoked. This mutation, identified in the gene EGFR T790M, appears to elevate lung cancer risk by 25 times when compared to those without it, as detailed in a new study published in the journal Science.
Among non-smokers, individuals with this mutation had roughly 62 times greater chances of developing lung cancer compared to non-smokers without the mutation.
The comprehensive study, conducted by researchers at Dana-Farber Cancer Institute and 23andMe Research Institute, analyzed data from over 3.3 million people. Interestingly, this gene variation did not show any increased risk for 17 other cancers that were examined.
Jaclyn LoPiccolo, a co-author of the study and lung cancer researcher at Dana-Farber, noted that current lung cancer screening largely depends on smoking history. She explained that the findings suggest that future screenings might also consider inherited genetic risks. If subsequent research supports these results, individuals with the EGFR T790M mutation could be identified via genetic testing and possibly receive personalized CT screenings. This could help detect lung cancers when they are still treatable.
The study identified that most individuals in the U.S. carrying this mutation likely trace back to a common ancestry related to British and Irish settlers in Southern Appalachia roughly 200–225 years ago. Although this mutation is still quite rare nationwide, affecting about one in 15,000 to 16,000 people, it seems to be more prevalent in some areas of Southern Appalachia, where estimates suggest that up to one in 2,000 may carry it.
LoPiccolo emphasized how most carriers inherit the mutation from a shared ancestral lineage, establishing a connection to the British and Irish settlers in America. She pointed out that this mutation became more frequent following a genetic bottleneck event in Southern Appalachia around 200 years ago, making it a fascinating case of how migration and genealogy can influence disease risk across generations.
While this study makes a strong case for the association between the mutation and lung cancer risk, it doesn’t definitively prove that genetic testing can enhance survival rates or lead to better health outcomes. Alexander Gusev, a quantitative geneticist at Dana-Farber, remarked on the significant impact of a single mutation, calling it perhaps the strongest mutation linked to increased cancer risk yet discovered. He reiterated that both smoking and this particular mutation heighten lung cancer risks, and combining the two intensifies the threat.
Researchers recommend that individuals with a robust family history of lung cancer, multiple lung nodules, or familial ties to certain southeastern U.S. regions should consider consulting a genetic counselor to discuss whether genetic testing or lung cancer screenings might be appropriate for them.
Despite these insightful findings, there are some limitations within the study. Due to the rarity of the mutation, researchers located a limited number of carriers among millions of participants, leaving the precise extent of the increased risk somewhat uncertain. Moreover, the study heavily relied on 23andMe participants, who may not reflect the wider population accurately. Since the mutation is notably more common in specific U.S. regions, the risk estimates may not apply uniformly.
Ultimately, while the study establishes a significant connection between this genetic mutation and lung cancer risk, it does not confirm that genetic testing can directly influence mortality or other health outcomes. Funding for the study came from the National Institutes of Health and the American Cancer Society.
