Individuals who have never smoked but carry a specific rare genetic mutation may face significantly higher risks of lung cancer. A new study reveals that carriers of the rare EGFR T790M mutation have a 62-fold increased risk of developing lung cancer compared to never-smokers without this mutation. When considering both smokers and non-smokers, individuals with the mutation still encounter a 25-fold increased risk.
Researcher Jaclyn LoPiccolo, MD, PhD, emphasized, “Lung cancer risk is often linked to smoking and environmental factors. However, the study highlights that inherited genetics can substantially increase risk.” For most common diseases, risk is distributed across various genetic variants with minimal effects. In this case, a single inherited mutation correlates with a significant increase in lung cancer risk.
Lung cancer is prevalent in both men and women in the U.S. The American Cancer Society anticipates approximately 229,410 new lung cancer diagnoses in 2026. Lung cancer remains the leading cause of cancer deaths in the U.S., responsible for about 20% of all cancer mortalities. Tobacco smoking leads as the primary risk factor, contributing to approximately 80% of lung cancer fatalities. Other non-modifiable risk factors include air pollution and family history.
Though family history is known to enhance lung cancer risk, genetic underpinnings remain poorly understood. Recent research published in Science assessed the EGFR T790M mutation by examining genetic and health data from over 3 million individuals. Results indicate a strong association between this gene variant and lung cancer risk.
Researchers traced the mutation’s history, suggesting it arrived in the U.S. via the Southern Appalachian region about 200 years ago. LoPiccolo stated, “Carriers of the EGFR T790M mutation faced about 25-fold higher odds of developing lung cancer compared to non-carriers. The risk was exceptionally high in never-smokers, with over 60-fold odds.” Scientists are hopeful that these findings will assist in identifying patients who could gain from genetic testing and lung cancer screening.
Due to its rarity, previous studies on this gene have been limited. However, access to over 3.3 million genotyped samples enabled researchers to estimate cancer risks linked to the variant. They also assessed its geographic distribution, uncovering a presence in 1 in 15,850 participants. In particular, the mutation was “significantly enriched” in the U.S., with a carrier frequency of 1 in 8,920 among descendants of British and Irish populations and later among African and Indigenous American ancestries. This points to the mutation’s European origin, arriving with British and Irish settlers during the colonial period.
LoPiccolo noted that further insights about the mutation and its implications for carriers are needed. “We aim to comprehend how lung cancer risk evolves with age for mutation carriers, their lifetime risk, and why some develop cancer while others do not. This includes exploring genetic and environmental influences on risk modification.” Ultimately, the objective is to leverage this data for guiding CT screenings to identify at-risk individuals effectively.
Do you have a health concern? Have questions about cancer? Email [email protected] for expert advice or feature opportunities. Reference: Jaclyn LoPiccolo et al., Germline EGFR T790M mutation and lung cancer risk. Science 393, eaec0473 (2026). DOI:10.1126/science.aec0473. Contact Newsweek editors on this story: Kara Dolman and Emma Lee-Sang.