WASHINGTON / RankWire.AI / – A rare inherited genetic mutation has been found to increase an individual’s overall likelihood of developing lung cancer by about 25 times, with a risk increase of roughly 60 times among those who have never smoked, according to a study published in the journal Science. The research, a collaboration between the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed de-identified genomic data from over 3.3 million individuals. The investigators identified the germline variant, known as EGFR T790M, as one of the most potent inherited risk factors for lung cancer uncovered so far.
This mutation is located in the epidermal growth factor receptor gene, which controls cell growth and division throughout lung tissue. Although somatic EGFR mutations acquired during life are recognized as drivers of non-small cell lung cancer, the T790M germline variant is inherited at birth and found in every cell. Data from the National Cancer Institute indicates that the mutation occurs in approximately 1 out of every 15,850 people in the United States. Lead author Dr. Jaclyn LoPiccolo pointed out that carrying this variant raises the odds of lung cancer roughly 62 times in individuals who have never smoked, compared to about 11 times in those with a history of smoking.
Gene genealogy analysis revealed that the EGFR T790M mutation is disproportionately concentrated among populations in the Southern Appalachian regions of Tennessee and Alabama. Evolutionary geneticists traced the mutation back to British and Irish settlers who migrated to North America during colonial times, with its prevalence increasing after a genetic bottleneck roughly 200 years ago. Senior study author Dr. Pasi A. Jänne stressed that although lung cancer screening primarily depends on tobacco exposure, identifying significant genetic risk factors could pave the way for targeted low-dose computed tomography screening for non-smokers carrying the mutation.
Dana-Farber Cancer Institute’s Research Involves 3.3 Million Genomes
Supported by the National Institutes of Health, the study confirmed through preclinical and clinical trials that the mutation has a strong specific link to lung cancer, without showing significant associations with 17 other common cancers evaluated in the dataset. Oncologists noted that while tobacco use remains the primary cause of lung cancer overall, the rising incidence of lung cancer among non-smokers is becoming a global health concern. Pharmaceutical companies, including AstraZeneca, are actively working on targeted tyrosine kinase inhibitors like Tagrisso to treat lung cancers with EGFR mutations when tumors progress.
Co-senior author Dr. Alexander Gusev noted that the study exemplifies how a single inherited point mutation can have an exceptionally significant impact on disease risk. Medical experts advise that individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia seek guidance from genetic counselors. Researchers highlighted that carrying the mutation does not automatically result in a lung cancer diagnosis, as environmental factors and secondary genetic changes also influence whether cancer develops over a lifetime.
EGFR Gene’s Role in Cell Growth and Division
The research team aims to expand observational studies through the ongoing INHERIT Study to examine additional inherited EGFR variants in diverse racial groups. This longitudinal research will focus on uncovering specific environmental triggers and secondary genomic alterations that determine why some carriers develop tumors while others remain asymptomatic.
Detailed results regarding population genetics, risk assessments, and screening guidelines are accessible through peer-reviewed medical repositories and institutional release portals. Future updates on biomarker data will be presented by clinical researchers at international oncology conferences to help shape upcoming screening recommendations.