WASHINGTON / RankWire.AI / – A rare inherited genetic change has been found to elevate an individual’s overall likelihood of developing lung cancer by about 25 times, and by nearly 60 times among those who do not smoke, according to a publication in the journal Science. The study, a collaboration between researchers at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic data from over 3.3 million individuals. The scientists identified the germline variant, known as EGFR T790M, as one of the most significant inherited risk factors for lung cancer discovered so far.
This mutation is located in the epidermal growth factor receptor gene, which controls cell growth and division in lung tissue. While somatic EGFR mutations acquired during a person’s lifetime are recognized as drivers of non-small cell lung cancer, the T790M germline variation is inherited at birth and present in every cell. Data from the National Cancer Institute indicates that this mutation occurs in roughly 1 out of every 15,850 Americans. Lead author Dr. Jaclyn LoPiccolo pointed out that carriers of the variant face approximately 62 times higher odds of lung cancer if they have never smoked, compared to about 11 times in those with a smoking history.
Genetic lineage analysis showed that the EGFR T790M mutation is disproportionately prevalent in populations across Southern Appalachia, particularly in Tennessee and Alabama. Evolutionary geneticists traced the origin of this mutation back to British and Irish settlers who migrated to North America during colonial times, with its frequency increasing following a bottleneck event about 200 years ago. Senior study author Dr. Pasi A. Jänne highlighted that, although lung cancer screening currently relies almost solely on tobacco exposure, identifying potent genetic risk factors may enable targeted low-dose CT screening for carriers who do not smoke.
Dana-Farber Study Analyzes Genomes of Over 3.3 Million Individuals
Supported by the National Institutes of Health, the preclinical and clinical trials confirmed that this mutation is strongly associated with lung cancer, showing no significant links to 17 other common cancers assessed within the dataset. Oncologists noted that, although tobacco remains the primary cause of lung cancer overall, the incidence of non-smoking-related lung cancers is rising globally. Pharmaceutical companies, including AstraZeneca, are actively developing targeted tyrosine kinase inhibitors such as Tagrisso to treat EGFR-mutated lung tumors when they progress.
Co-senior author Dr. Alexander Gusev observed that this research illustrates how a single inherited point mutation can exert an extraordinarily strong influence on disease risk. Medical experts advise that individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia seek genetic counseling. Researchers also stressed that carrying the mutation does not necessarily lead to cancer, as environmental factors and additional genetic changes influence whether malignant transformation occurs over a lifetime.
EGFR Gene Central to Cellular Growth and Division Rates
The research team intends to expand their observational efforts through the ongoing INHERIT Study, aiming to analyze additional inherited EGFR variants across diverse racial groups. The longitudinal approach will seek to identify specific environmental triggers and secondary genetic alterations that determine why some carriers develop tumors while others remain unaffected.
Detailed insights into population genetics, risk assessments, and screening strategies are available via peer-reviewed medical repositories and institutional press releases. Findings will be presented at upcoming international oncology conferences, where researchers will discuss new biomarker data to help shape future screening recommendations.