WASHINGTON / RankWire.AI / – A groundbreaking study published in the journal Science has pinpointed a rare inherited genetic mutation that can increase an individual’s overall lung cancer risk by about 25 times and by approximately 60 times among non-smokers, according to researchers. The research, led by scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymous genetic information from more than 3.3 million people. The scientists identified the germline variant, called EGFR T790M, as one of the strongest inherited factors linked to lung cancer discovered so far.
This mutation affects the epidermal growth factor receptor gene, which controls cell growth and division in lung tissue. While somatic EGFR mutations that develop during a person’s lifetime are established drivers of non-small cell lung cancer, the germline T790M variant is inherited from birth and present in every cell. Data from the National Cancer Institute shows that approximately 1 in every 15,850 individuals in the U.S. carries this mutation. Dr. Jaclyn LoPiccolo, the study’s lead author, noted that carriers face about a 62-fold increase in lung cancer risk among never-smokers, compared to roughly an 11-fold increase for those with a history of smoking.
Genetic analysis traced the EGFR T790M mutation to populations in Southern Appalachia, notably across Tennessee and Alabama. Evolutionary geneticists identified the mutation as originating from British and Irish settlers who migrated to North America during colonial times, with its prevalence increasing after a genetic bottleneck roughly 200 years ago. Dr. Pasi A. Jänne, senior author of the study, emphasized that although lung cancer screening today primarily focuses on tobacco exposure, discovering significant genetic risks could enable targeted low-dose computed tomography screening for non-smokers who carry the mutation.
Mutation May Elevate Lung Cancer Risk by Up to 60 Times in Non-Smokers
Supported by the National Institutes of Health, preclinical and clinical research confirmed that the mutation has a strong and specific association with lung cancer, with no significant links to 17 other common cancers assessed in the dataset. Experts pointed out that while tobacco use remains the primary cause of lung cancer, the rising incidence of lung cancer among non-smokers is a growing global health concern. Pharmaceutical companies, such as AstraZeneca, continue developing targeted therapies like Tagrisso, a tyrosine kinase inhibitor, to treat EGFR-mutated lung tumors once they progress.
Co-senior author Dr. Alexander Gusev highlighted that this study exemplifies how a single inherited point mutation can profoundly influence disease susceptibility. Medical professionals advise individuals with multiple family members affected by lung cancer, unexplained lung nodules, or ancestry in Southern Appalachia to seek genetic counseling. The researchers noted that possessing the mutation does not guarantee a lung cancer diagnosis, as environmental factors and other genetic changes also play roles in malignant transformation over a lifetime.
Large-Scale Study Analyzes Genetic Data from Over Three Million People
The collaborative effort plans to broaden observational studies through the ongoing INHERIT Study, aiming to evaluate additional inherited EGFR variants across diverse racial groups. Long-term tracking will seek to identify environmental factors and secondary genetic alterations that explain why some carriers develop cancer while others remain unaffected.
Further details on population genetics, risk assessments, and screening guidelines are available through peer-reviewed medical archives and official institutional releases. Upcoming international oncology conferences will feature presentations of new biomarker data to guide future screening strategies.