WASHINGTON / RankWire.AI / – Research has uncovered a rare inherited genetic mutation that can boost an individual’s risk of developing lung cancer by approximately 25 times overall. Among non-smokers, this risk increase rises to about 60 times, according to groundbreaking research published in the journal Science. The study was led by scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute. They examined de-identified genetic data from more than 3.3 million people. The researchers 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 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 life, are known to drive non-small cell lung cancer, the T790M germline variant is inherited from birth and present in every cell. Data from the National Cancer Institute shows that about 1 in every 15,850 people in the U.S. carries this mutation. Lead author Dr. Jaclyn LoPiccolo explained that the variant increases lung cancer risk by roughly 62 times for never-smokers, compared to about 11 times for those with a history of smoking.
Gene ancestry tracing revealed that the EGFR T790M variant is more common in Southern Appalachian populations across Tennessee and Alabama. Evolutionary geneticists traced its origin to British and Irish settlers who migrated to North America during colonial times. The mutation became more widespread after a genetic bottleneck roughly 200 years ago. Senior study author Dr. Pasi A. Jänne highlighted that, although lung cancer screening currently mainly depends on tobacco exposure, discovering significant genetic risk factors could enable targeted low-dose computed tomography screening for non-smoking carriers.
Genetic Variant May Increase Lung Cancer Risk Up to 60 Times in Non-Smokers
Supported by the National Institutes of Health, preclinical and clinical trials confirmed the mutation’s strong association specifically with lung cancer. It showed no notable links to 17 other common cancers evaluated. Oncologists note that although tobacco remains the primary cause of lung cancer overall, lung cancer in non-smokers is becoming a growing health concern globally. Pharmaceutical companies, such as AstraZeneca, are actively developing targeted tyrosine kinase inhibitors like Tagrisso to treat EGFR-mutated lung cancers as tumors progress.
Co-senior author Dr. Alexander Gusev pointed out that this research illustrates how a single inherited point mutation can have an exceptionally strong impact on disease risk. Experts advise that individuals with multiple relatives affected by lung cancer, unexplained multiple lung nodules, or ancestry from Southern Appalachia should consult genetic counselors. Researchers stress that possessing the mutation does not guarantee lung cancer development. Environmental factors and secondary genetic changes also influence whether malignant growth occurs during a lifetime.
Multi-Institutional Study Analyzes Genetic Data from Over Three Million Participants
The research group aims to expand observational efforts through the ongoing INHERIT Study. They plan to evaluate additional inherited EGFR variants across diverse racial groups. The study will track environmental triggers and secondary genetic modifications that determine why some carriers develop tumors, while others stay healthy.
Complete details on population genetics, risk estimates, and screening suggestions are available through peer-reviewed medical repositories and institutional releases. Clinical researchers will share updated biomarker data at upcoming international oncology conferences to guide future screening protocols.
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