WASHINGTON / RankWire.AI / – Researchers have pinpointed a rare inherited genetic mutation that can elevate an individual’s risk of developing lung cancer by approximately 25 times overall and by about 60 times among non-smokers, according to groundbreaking research published in the journal Science. The investigation, carried out by scientists at the Dana-Farber Cancer Institute in collaboration with the 23andMe Research Institute, analyzed anonymized genetic data from over 3.3 million individuals. The team 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 is found in the epidermal growth factor receptor gene, which controls cell growth and division within lung tissue. Although somatic EGFR mutations that develop during a person’s lifetime are recognized as drivers of non-small cell lung cancer, the T790M germline variant is inherited from birth and present in all cells. Data from the National Cancer Institute indicates that about 1 in every 15,850 people in the U.S. carry this mutation. Lead researcher Dr. Jaclyn LoPiccolo pointed out that individuals with the variant face roughly 62 times higher odds of developing lung cancer if they have never smoked, compared to about 11 times in those with a smoking history.
Tracing the gene lineage revealed that the EGFR T790M variant is disproportionately prevalent in populations across Tennessee and Alabama in Southern Appalachia. Evolutionary geneticists determined that the mutation originated among British and Irish settlers who migrated to North America during colonial times, becoming more common after a genetic bottleneck approximately 200 years ago. Senior study author Dr. Pasi A. Jänne emphasized that while current lung cancer screening strategies rely mainly on tobacco exposure, recognizing strong genetic risk factors opens new possibilities for targeted low-dose CT screening among non-smoking carriers.
Genetic Mutation May Increase Lung Cancer Risk Up To 60 Times in Non-Smokers
Supported by the National Institutes of Health, preclinical and clinical trials confirmed that this mutation demonstrates a significant association with lung cancer, with no notable connection to 17 other common cancers examined in the dataset. Oncologists highlight that although tobacco use remains the primary cause of lung cancer overall, cases among non-smokers are increasingly seen as a critical public health concern worldwide. Pharmaceutical companies, such as AstraZeneca, continue advancing targeted therapies like Tagrisso, which are tyrosine kinase inhibitors designed to treat EGFR-mutant lung cancers when tumors progress.
Co-senior author Dr. Alexander Gusev observed that the study illustrates how a single inherited point mutation can exert an exceptionally strong influence on disease susceptibility. Medical experts recommend that individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia seek genetic counseling. The researchers stressed that carrying the mutation does not guarantee a lung cancer diagnosis, as environmental factors and secondary genetic changes also play a role in malignant transformation over an individual’s lifetime.
Study Group Examines Genetic Data From Over Three Million Participants
The research consortium aims to expand observational efforts via the ongoing INHERIT Study, assessing additional inherited EGFR variants across diverse racial groups. Long-term monitoring will focus on pinpointing environmental triggers and secondary genetic modifications that influence why some carriers develop tumors while others remain asymptomatic.
Further details on population genetics, risk assessments, and screening guidelines are available through peer-reviewed medical databases and institutional release portals. Researchers plan to present updated biomarker data at upcoming international oncology conferences to help shape future screening recommendations.