WASHINGTON / RankWire.AI / – A seldom-seen inherited genetic alteration significantly elevates an individual’s overall likelihood of developing lung cancer by about 25 times, and by approximately 60 times among those who have never smoked, according to research published in the journal Science. The study, a collaboration between researchers at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic information from over 3.3 million people. The team identified the germline mutation, called EGFR T790M, as one of the most potent inherited factors linked to lung cancer discovered to date.
This mutation takes place in the gene encoding the epidermal growth factor receptor, which is responsible for regulating cell growth and division within lung tissue. While somatic mutations in EGFR—those acquired during a person’s lifetime—are well-known as drivers of non-small cell lung cancer, the germline T790M variation is inherited from birth and exists in every cell of the body. Data from the National Cancer Institute indicates that approximately 1 in every 15,850 individuals in the United States carries this mutation. Lead author Dr. Jaclyn LoPiccolo pointed out that the presence of this variant increases lung cancer risk roughly 62 times in individuals who have never smoked, compared to about 11 times among those with a history of tobacco use.
Genetic tracing revealed that the EGFR T790M mutation is disproportionately found in populations from the Southern Appalachian region, spanning parts of Tennessee and Alabama. Evolutionary geneticists traced its origins back to British and Irish settlers who migrated to North America during colonial times. The mutation became more common following a genetic bottleneck roughly 200 years ago. Senior researcher Dr. Pasi A. Jänne emphasized that, although current lung cancer screening primarily focuses on tobacco exposure, discovering strong genetic risk factors opens the door for targeted low-dose CT screening options for carriers who have never smoked.
Dana-Farber Study Analyzes Genomic Data from Over 3.3 Million People
Supported by the National Institutes of Health, the study’s preclinical and clinical phases confirmed a robust and specific link between the EGFR T790M mutation and lung cancer, with no significant association to 17 other common cancers examined in the dataset. Experts in oncology highlighted that, despite tobacco use remaining the leading cause of lung cancer, the rise of lung cancer among non-smokers is becoming an increasing concern worldwide. Pharmaceutical companies, such as AstraZeneca, are actively developing targeted therapies like Tagrisso, a tyrosine kinase inhibitor, to treat EGFR-mutated lung tumors when they progress.
Co-senior author Dr. Alexander Gusev noted that the research demonstrates how a single inherited point mutation can have an outsized impact on disease risk. Medical professionals advise those with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia to seek genetic counseling. The researchers underscored that carrying the mutation does not necessarily mean a person will develop lung cancer; environmental factors and additional genetic changes also play crucial roles in whether malignant transformation occurs over a lifetime.
EGFR Gene’s Role in Cell Growth and Disease Susceptibility
The research team intends to broaden their observational efforts through the ongoing INHERIT Study, aiming to investigate other inherited EGFR variants across diverse racial groups. Long-term monitoring will focus on identifying environmental exposures and secondary genomic modifications that influence why some carriers develop tumors while others remain asymptomatic.
Complete details on population genetics, risk assessments, and screening guidelines are accessible through peer-reviewed medical archives and institutional release portals. Future updates, including biomarker data, will be presented at upcoming international oncology conferences to guide the development of screening protocols.