WASHINGTON / RankWire.AI / – A rare inherited genetic mutation has been found to increase an individual’s overall likelihood of developing lung cancer by approximately 25 times, and by about 60 times among non-smokers, according to a study published in the journal Science. The research, conducted collaboratively by investigators at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed de-identified genomic data from over 3.3 million individuals. The scientists identified the germline variant, known as EGFR T790M, as one of the most potent inherited risk factors for lung cancer discovered so far.
This mutation occurs within the epidermal growth factor receptor gene, which is responsible for regulating cell growth and division in lung tissue. While somatic EGFR mutations acquired during a person’s lifetime are established drivers of non-small cell lung cancer, the T790M germline variant is inherited at birth and present in every cell. Data from the National Cancer Institute indicates that approximately 1 in every 15,850 people in the United States carries this mutation. Lead author Dr. Jaclyn LoPiccolo pointed out that carrying the variant increases lung cancer risk about 62-fold in never-smokers, compared to roughly 11-fold in those with a history of smoking.
Genetic tracing revealed that the EGFR T790M mutation is disproportionately concentrated 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. It became more prevalent following a genetic bottleneck roughly 200 years ago. Senior study author Dr. Pasi A. Jänne emphasized that although lung cancer screening currently largely depends on tobacco exposure, identifying strong genetic risk factors could open new avenues for targeted low-dose computed tomography screening in carriers who do not smoke.
Dana-Farber Study Analyzes Genomes of Over 3.3 Million Subjects
Supported by the National Institutes of Health, the preclinical and clinical trials confirmed that the mutation exhibits a notable specific association with lung cancer, with no significant links to 17 other common cancers examined in the dataset. Oncologists note that although tobacco consumption remains the primary cause of lung cancer overall, the increasing incidence of non-smoking-related lung cancer has become a significant global health concern. Pharmaceutical companies such as AstraZeneca continue advancing targeted therapies like Tagrisso, a tyrosine kinase inhibitor, to treat EGFR-mutant lung cancers when tumors progress.
Co-senior author Dr. Alexander Gusev observed that this study highlights how a single inherited point mutation can exert a remarkably strong influence on disease susceptibility. Experts recommend that individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or those with ancestral roots in Southern Appalachia seek advice from genetic counselors. The researchers stress that possessing this mutation does not necessarily mean a person will develop lung cancer, as environmental factors and secondary genetic modifications also play crucial roles in whether malignant transformation occurs over a lifetime.
EGFR Gene’s Role in Cell Growth Regulation and Cancer Development
The research team plans to expand observational efforts through the ongoing INHERIT Study, aiming to assess additional inherited EGFR variants across racially diverse groups. Long-term monitoring will focus on identifying specific environmental factors and secondary genetic changes that influence why some carriers develop tumors while others remain unaffected.
Detailed results related to population genetics, risk assessments, and screening recommendations are available through peer-reviewed medical repositories and institutional information portals. Researchers will also present updated biomarker data at upcoming international oncology conferences to guide future screening protocols.