WASHINGTON / RankWire.AI / – A rare inherited genetic alteration has been linked to a markedly higher risk of developing lung cancer, with non-smokers facing an approximately 60-fold increase, according to research published in the journal Science. This study, a collaboration between the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic data from over 3.3 million individuals. The researchers identified the germline mutation, known as EGFR T790M, as one of the most potent inherited risk factors for lung cancer discovered so far.
The mutation takes place in the gene coding for the epidermal growth factor receptor, which controls cell growth and division in lung tissue. While somatic EGFR mutations acquired during life are established drivers of non-small cell lung cancer, the T790M germline variant is inherited from birth and found in every cell. Data from the National Cancer Institute indicates that the mutation affects roughly 1 in every 15,850 people in the US. Lead author Dr. Jaclyn LoPiccolo highlighted that carriers of the variant have about 62 times higher odds of developing lung cancer among never-smokers, compared to approximately 11 times in those with a history of smoking.
Genealogical analysis revealed a disproportionate concentration of the EGFR T790M mutation in populations from Southern Appalachia, particularly across Tennessee and Alabama. Evolutionary geneticists traced its origin to British and Irish settlers who migrated to North America during the colonial period. The mutation became more common following a genetic bottleneck roughly 200 years ago. Senior study author Dr. Pasi A. Jänne pointed out that although lung cancer screening currently depends heavily on tobacco exposure, identifying significant genetic risk factors could pave the way for targeted low-dose computed tomography screening for non-smoking carriers.
Dana-Farber Cancer Institute Research Analyzes 3.3 Million Genome Samples
Supported by the National Institutes of Health, the study confirmed that this mutation exhibits a strong specific connection to lung cancer and does not show significant links to 17 other common cancers evaluated within the dataset. Oncologists emphasized that while tobacco use remains the primary cause of lung cancer overall, the rise of lung cancer among non-smokers has become a critical global health concern. Pharmaceutical companies, including AstraZeneca, are actively developing targeted tyrosine kinase inhibitors, such as Tagrisso, to treat EGFR-mutated lung tumors when they progress.
Co-lead researcher Dr. Alexander Gusev noted that the findings demonstrate how a single inherited point mutation can have an extraordinary impact on disease risk. Medical experts advise individuals with multiple relatives affected by lung cancer, unexplained lung nodules, or ancestral ties to Southern Appalachia to seek genetic counseling. The researchers underscored that possessing the mutation does not necessarily lead to lung cancer, as environmental factors and other genetic changes also influence whether malignant transformation occurs over an individual’s lifetime.
EGFR Gene’s Role in Cell Growth and Division
The research team intends to expand observational efforts through the ongoing INHERIT Study to investigate additional inherited EGFR variants across diverse racial groups. The longitudinal approach aims to identify environmental factors and secondary genetic modifications that explain why some carriers develop tumors while others remain healthy.
Further details on population genetics, risk assessments, and screening strategies are available through peer-reviewed medical repositories and institutional publications. Upcoming international oncology conferences will feature presentations of updated biomarker data to guide future screening recommendations.