WASHINGTON / RankWire.AI / – According to a study published in the journal Science, a rare inherited genetic mutation significantly increases an individual’s overall risk of developing lung cancer by about 25 times, and by approximately 60 times among non-smokers. The research, a collaboration between Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic data from over 3.3 million people. The investigators identified the germline variant, known as EGFR T790M, as one of the most potent inherited factors linked to lung cancer identified to date.
This mutation is found in the epidermal growth factor receptor gene, which is responsible for controlling cell growth and division in lung tissue. While somatic mutations in EGFR acquired during a person’s lifetime are known to be key drivers of non-small cell lung cancer, the T790M germline variant is inherited from birth and present in every cell. Data from the National Cancer Institute indicates that about 1 in every 15,850 people in the U.S. carry this mutation. Lead researcher Dr. Jaclyn LoPiccolo pointed out that carriers of the variant have roughly 62 times higher odds of developing lung cancer among never-smokers, compared to about 11 times for those with a history of smoking.
Genetic lineage analysis shows that the EGFR T790M mutation is disproportionately common among populations in Southern Appalachia, specifically across Tennessee and Alabama. Evolutionary geneticists traced the mutation back to British and Irish settlers who migrated to North America during colonial times, with its frequency increasing following a genetic bottleneck roughly 200 years ago. Dr. Pasi A. Jänne, a senior author of the study, stressed that although current lung cancer screening primarily targets tobacco users, identifying strong genetic risk factors could allow for targeted low-dose computed tomography screening for non-smoking carriers.
Dana-Farber Cancer Institute’s Research Analyzes 3.3 Million Genomes
Supported by the National Institutes of Health, preclinical and clinical trials confirmed that this mutation exhibits a strong specific link to lung cancer, with no significant association observed with 17 other common cancers evaluated in the dataset. Oncologists noted that although tobacco exposure remains the leading cause of lung cancer overall, the rise of lung cancer among non-smokers is becoming a global health concern. Companies like AstraZeneca are actively developing targeted therapies such as tyrosine kinase inhibitors like Tagrisso to treat EGFR-mutated lung cancers, especially as tumors progress.
Co-senior author Dr. Alexander Gusev highlighted that this study demonstrates how a single inherited point mutation can have a profound effect on disease susceptibility. Medical professionals advise individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia to seek genetic counseling. Researchers also emphasized that possessing the mutation does not guarantee lung cancer development, as environmental factors and additional genetic changes influence whether malignant transformation occurs during a lifetime.
EGFR Gene’s Role in Regulating Cell Growth
Plans are underway to expand observational efforts through the ongoing INHERIT Study, which will examine additional inherited EGFR variants across racially diverse groups. Longitudinal studies will aim to identify environmental triggers and secondary genetic modifications that explain why some carriers develop tumors while others remain healthy.
Further detailed data on population genetics, risk assessments, and screening protocols can be found through peer-reviewed medical repositories and institutional release portals. Future updates, including biomarker data, will be presented at upcoming international oncology conferences to shape new screening standards.