WASHINGTON / RankWire.AI / – Researchers have uncovered a rare inherited genetic alteration that can boost an individual’s likelihood of developing lung cancer by approximately 25 times overall. Among non-smokers, this increase can be as high as 60 times, according to groundbreaking research published in the journal Science. The investigation, carried out by scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genetic information from over 3.3 million individuals. They identified the germline variant, known as EGFR T790M, as one of the strongest inherited risk factors for lung cancer found 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 life are recognized as drivers of non-small cell lung cancer, the T790M germline variant is inherited from birth and present in every cell of the body. Data from the National Cancer Institute shows that about 1 in every 15,850 people in the United States carries this mutation. Lead researcher Dr. Jaclyn LoPiccolo highlighted that those with the variant face about a 62-fold increase in lung cancer risk among never-smokers, compared to roughly 11 times in people with a history of smoking.
Genetic lineage studies indicated that the EGFR T790M mutation is disproportionately common in populations from Southern Appalachia, specifically across Tennessee and Alabama. Evolutionary geneticists traced the origin of this mutation to British and Irish settlers who migrated to North America during the colonial period. The mutation became more prevalent following a genetic bottleneck approximately 200 years ago. Senior author Dr. Pasi A. Jänne emphasized that, while current lung cancer screening primarily targets tobacco exposure, recognizing strong genetic risk factors opens the door to targeted low-dose computed tomography screening for non-smoking carriers.
Gene May Increase Lung Cancer Risk Up to 60 Times in Individuals Who Never Smoked
Supported by the National Institutes of Health, preclinical and clinical studies confirmed that the mutation has a significant specific association with lung cancer. It showed no notable link to 17 other common cancers examined in the dataset. Oncologists noted that, although tobacco use remains the leading cause of lung cancer overall, non-smoking-related lung cancer is a growing global health concern. 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 stated that the study illustrates how a single inherited point mutation can have an exceptionally powerful impact on disease risk. Medical experts recommend that individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or ancestral roots in Southern Appalachia consult with genetic counselors. The researchers also stressed that carrying the mutation does not guarantee a lung cancer diagnosis, as environmental factors and other genetic changes influence whether malignant transformation occurs over a lifetime.
Multi-Institutional Study Examines Genetic Data from Over Three Million Participants
The research group plans to expand observational efforts through the ongoing INHERIT Study. Their goal is to analyze additional inherited EGFR variants across diverse racial and ethnic groups. Long-term tracking aims to identify specific environmental triggers and secondary genetic alterations that influence why some carriers develop tumors while others remain unaffected.
Complete details on population genetics, risk assessments, and screening guidelines are available through peer-reviewed medical repositories and institutional release platforms. Future updates on biomarker data will be presented at upcoming international oncology conferences to guide enhanced screening protocols.