WASHINGTON / RankWire.AI / – Researchers have pinpointed a rare inherited genetic alteration 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, examined anonymized genetic information from over 3.3 million people. The scientists identified the germline mutation, known as EGFR T790M, as one of the most significant inherited factors linked to lung cancer discovered to date.
This mutation affects the epidermal growth factor receptor gene, which governs cell growth and division within lung tissue. While somatic EGFR mutations acquired during life are recognized as key drivers of non-small cell lung cancer, the inherited T790M germline variant is present from birth and exists in every cell. Data from the National Cancer Institute indicates that the mutation occurs in about 1 in every 15,850 individuals in the United States. Lead author Dr. Jaclyn LoPiccolo stated that possessing the variant increases the likelihood of lung cancer roughly 62 times in those who have never smoked, compared to around 11 times in people with a smoking history.
Genetic lineage analysis revealed that the EGFR T790M mutation is disproportionately concentrated in populations across Tennessee and Alabama’s Southern Appalachian region. Evolutionary geneticists traced the mutation’s origin back to British and Irish settlers who migrated to North America during colonial times, with its prevalence increasing following a genetic bottleneck approximately 200 years ago. Senior study author Dr. Pasi A. Jänne emphasized that, although lung cancer screening is primarily based on tobacco use, recognizing strong genetic risk factors offers new opportunities for targeted low-dose computed tomography screening in carriers who have never smoked.
Gene Could Elevate Lung Cancer Risk Nearly 60 Times in Non-Smokers
Supported by the National Institutes of Health, preclinical and clinical trials confirmed that the mutation has a strong specific association with lung cancer, showing no significant correlation with 17 other common cancers evaluated in the study. Oncologists highlighted that while tobacco remains the main cause of lung cancer overall, the incidence among non-smokers is a growing concern worldwide. Pharmaceutical companies, including AstraZeneca, are actively developing targeted tyrosine kinase inhibitors like Tagrisso to treat EGFR-mutated lung cancers when tumors progress.
Co-senior author Dr. Alexander Gusev remarked that this research demonstrates how a single inherited point mutation can have an exceptionally strong impact on disease susceptibility. Medical professionals suggest that individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia consult with genetic counselors. The researchers stressed that carrying the mutation does not guarantee a lung cancer diagnosis, as environmental factors and additional genetic changes also influence whether malignant transformation occurs over time.
Multicenter Study Analyzes Genetic Data from Over Three Million Participants
The research alliance aims to expand observational efforts through the ongoing INHERIT Study to examine additional inherited EGFR variants across racially diverse populations. Long-term monitoring will seek to identify specific environmental factors and secondary genetic alterations that determine why some carriers develop tumors while others do not exhibit any symptoms.
Detailed results on population genetics, relative risk estimates, and screening guidelines remain available through peer-reviewed medical databases and institutional release channels. Future updates on biomarker data will be presented by clinical researchers at upcoming international oncology conferences to shape upcoming screening policies.