WASHINGTON / RankWire.AI / – A seldom-found inherited genetic alteration has been shown to increase an individual’s overall likelihood of developing lung cancer by about 25 times, with an even higher risk—roughly 60 times—in those who have never smoked, according to a report published in the journal Science. The research, conducted collaboratively by scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic information from over 3.3 million people. The team pinpointed the germline mutation, called EGFR T790M, as one of the most potent inherited factors linked to lung cancer identified to date.
This mutation occurs within the gene responsible for encoding the epidermal growth factor receptor, which plays a crucial role in controlling cell growth and division within lung tissue. Although somatic mutations of EGFR acquired during a person’s life are recognized as key drivers of non-small cell lung cancer, the germline variant T790M is inherited at birth, present in every cell. Data from the National Cancer Institute indicates that this mutation affects roughly 1 in every 15,850 individuals in the United States. Lead author Dr. Jaclyn LoPiccolo pointed out that carrying this variant increases lung cancer risk by approximately 62 times in people who have never smoked, versus around 11 times for those with a history of tobacco use.
Genetic analysis of family lineages revealed that the EGFR T790M mutation is disproportionately concentrated among populations in Southern Appalachia, specifically across Tennessee and Alabama. Evolutionary geneticists traced the origin of this mutation to British and Irish settlers who moved to North America during colonial times, with its frequency rising after a genetic bottleneck about 200 years ago. Senior researcher Dr. Pasi A. Jänne highlighted that, although lung cancer screening currently focuses mainly on tobacco exposure, recognizing significant genetic risks could pave the way for targeted low-dose computed tomography screening for carriers who do not smoke.
Dana-Farber’s Study Analyzes Genomic Data from Over 3.3 Million Subjects
Supported by the National Institutes of Health, the study’s preclinical and clinical phases confirmed a strong specific connection between the mutation and lung cancer, with no meaningful association observed for 17 other common cancers included in the dataset. Oncology experts noted that while tobacco remains the primary cause of lung cancer, the rising incidence among non-smokers has made non-smoking-related lung cancer an increasing concern worldwide. Pharmaceutical companies, such as AstraZeneca, continue to develop targeted tyrosine kinase inhibitors like Tagrisso to treat EGFR-mutated lung tumors when they progress.
Co-senior author Dr. Alexander Gusev remarked that this research exemplifies how a single inherited point mutation can exert a notably strong influence on disease susceptibility. Medical professionals advise that individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral links to Southern Appalachia should seek genetic counseling. Researchers stressed that possessing the mutation does not necessarily mean a person will develop lung cancer, as environmental factors and secondary genetic modifications also impact whether malignant transformation occurs during a lifetime.
Epidermal Growth Factor Receptor Gene Influences Cell Division Rates
The research team aims to broaden observational efforts through the ongoing INHERIT Study, examining additional inherited variants of EGFR across diverse racial populations. Long-term monitoring will focus on identifying specific environmental exposures and secondary genetic changes that determine why some carriers develop tumors while others do not show symptoms.
Further detailed findings, including population genetic data, risk assessments, and screening guidance, are available through peer-reviewed medical repositories and institutional release portals. Researchers plan to present updated biomarker data at upcoming international oncology conferences to help shape future screening protocols.