WASHINGTON / RankWire.AI / – A groundbreaking study published in the journal Science reveals a rare inherited genetic mutation that can elevate an individual’s overall risk of developing lung cancer by approximately 25 times and up to 60 times in non-smokers, according to recent research. The investigation, led by researchers at the Dana-Farber Cancer Institute in collaboration with the 23andMe Research Institute, examined anonymized genetic data from more than 3.3 million people. The team pinpointed the germline variant, known as EGFR T790M, as one of the most significant inherited risk factors for lung cancer identified so far.
This mutation is located within the epidermal growth factor receptor gene, which plays a critical role in controlling cell growth and division within lung tissue. While somatic EGFR mutations acquired during a person’s lifetime are established contributors to non-small cell lung cancer, the T790M germline variant is inherited from birth and is present in every cell. Data from the National Cancer Institute indicates that the mutation occurs in roughly 1 out of every 15,850 individuals in the United States. According to lead author Dr. Jaclyn LoPiccolo, carrying this variant increases lung cancer risk about 62 times in individuals who have never smoked, compared to roughly 11 times among those with a history of tobacco use.
Genealogical analysis revealed that the EGFR T790M mutation is disproportionately prevalent among populations in Southern Appalachia, particularly across Tennessee and Alabama. Evolutionary geneticists traced the origin of the mutation to British and Irish settlers who immigrated to North America during colonial times. The mutation’s frequency increased following a genetic bottleneck approximately 200 years ago. Senior study author Dr. Pasi A. Jänne highlighted that although current lung cancer screening primarily targets tobacco users, the identification of strong genetic risk factors could enable targeted low-dose computed tomography screening for non-smoking carriers.
Genetic Mutation May Amplify Lung Cancer Risk by Up to 60 Times in Non-Smokers
Supported by preclinical and clinical trials funded by the National Institutes of Health, the study confirmed that this mutation exhibits a strong specific link to lung cancer, showing no significant association with 17 other common cancers evaluated within the dataset. Oncologists pointed out that although tobacco remains the primary cause of lung cancer overall, the increasing prevalence of lung cancer among non-smokers makes it a major global health concern. Pharmaceutical companies, including AstraZeneca, are actively developing targeted therapies such as Tagrisso, a tyrosine kinase inhibitor, to treat lung cancers harboring EGFR mutations when tumors progress.
Co-senior author Dr. Alexander Gusev emphasized that this study demonstrates how a single inherited point mutation can exert an exceptionally strong influence on disease susceptibility. Medical professionals advise individuals with multiple relatives affected by lung cancer, unexplained multifocal lung nodules, or ancestral roots in Southern Appalachia to seek genetic counseling. Researchers clarified that possessing the mutation does not necessarily lead to lung cancer, as environmental factors and secondary genetic modifications also play critical roles in whether malignant transformation occurs over a lifetime.
A Multicenter Study Analyzes Genetic Data from Over Three Million Participants
The research consortium intends to expand its observational efforts through the ongoing INHERIT Study, which will investigate additional inherited EGFR variants across diverse racial and ethnic groups. Longitudinal analysis will focus on identifying environmental triggers and secondary genomic changes that influence why some carriers develop tumors while others remain unaffected.
Findings related to population genetics, risk assessment, and screening guidelines are available through peer-reviewed medical repositories and institutional release portals. Future biomarker data will be presented at international oncology conferences to guide the development of screening protocols and early detection strategies.