WASHINGTON / RankWire.AI / – A groundbreaking study published in the journal Science has revealed a rare inherited genetic mutation that can increase an individual’s risk of developing lung cancer by approximately 25 times overall, with a notable 60-fold increase among non-smokers. The research, carried out by scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute, examined anonymized genetic data from over 3.3 million individuals. The investigators identified the germline variant, known as EGFR T790M, as one of the most significant inherited risk factors for lung cancer identified to date.
This mutation is situated in the epidermal growth factor receptor gene, which oversees 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 is present in every cell. According to data from the National Cancer Institute, the mutation affects roughly 1 in every 15,850 individuals in the United States. Lead author Dr. Jaclyn LoPiccolo pointed out that carriers of this variant face about a 62 times higher chance of lung cancer among never-smokers, compared to approximately 11 times in those with a smoking history.
Genetic lineage analysis indicated a significant concentration of the EGFR T790M variant in populations across Southern Appalachia, particularly in parts of Tennessee and Alabama. Evolutionary geneticists traced the mutation back to British and Irish settlers who migrated to North America during colonial times, where the variant became more prevalent following a genetic bottleneck roughly 200 years ago. Dr. Pasi A. Jänne, senior author of the study, emphasized that although lung cancer screening is currently primarily based on tobacco use, recognizing strong genetic risk factors could pave the way for targeted low-dose computed tomography screening, especially for non-smoking carriers.
Genetic Variant Potentially Elevates Lung Cancer Risk in Non-Smokers by 60 Times
Supported by the National Institutes of Health, preclinical and clinical trials confirmed that this mutation shows a strong, specific connection to lung cancer, with no significant association found for 17 other common cancers evaluated. While tobacco use remains the leading cause of lung cancer, oncologists are increasingly focused on non-smoking-related cases, which are becoming a growing global health concern. Pharmaceutical companies, such as AstraZeneca, are actively developing targeted tyrosine kinase inhibitors like Tagrisso for treating EGFR-mutated lung cancers once tumors progress.
Dr. Alexander Gusev, co-senior author, noted that the research illustrates how a single inherited point mutation can exert an extraordinarily powerful influence on disease risk. Medical professionals advise individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia to seek genetic counseling. The researchers highlighted that possessing the mutation does not guarantee lung cancer development, as environmental factors and additional genetic modifications also play a role in whether malignant transformation occurs over a person’s lifetime.
Multicenter Study Examines Genetic Data from Over Three Million Participants
Plans are underway to expand observational efforts through the ongoing INHERIT Study, aiming to evaluate other inherited EGFR variants across diverse racial groups. The longitudinal approach will focus on identifying specific environmental factors and secondary genetic changes that influence why some carriers develop tumors while others remain asymptomatic.
Further details on population genetics, risk assessments, and screening recommendations are available through peer-reviewed medical repositories and official institutional releases. Upcoming international oncology conferences will feature presentations of new biomarker data to help shape future screening guidelines.