WASHINGTON / RankWire.AI / – A rare inherited genetic mutation has been shown to increase an individual’s overall likelihood of developing lung cancer approximately 25 times, with an increase of about 60 times among non-smokers, according to a study published in the journal Science. The research, carried out collaboratively by investigators at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed de-identified genomic data from more than 3.3 million individuals. The scientists identified the germline variant, known as EGFR T790M, as one of the strongest inherited risk factors for lung cancer discovered to date.
This mutation takes place in the epidermal growth factor receptor gene, which oversees cell growth and division within pulmonary tissue. While somatic EGFR mutations acquired 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 every cell. Data from the National Cancer Institute indicates that the mutation occurs in approximately 1 out of every 15,850 people in the United States. Lead author Dr. Jaclyn LoPiccolo highlighted that carrying this variant increases lung cancer risk roughly 62 times in never-smokers, compared to about 11 times in those with a smoking history.
Gene tracing studies revealed that the EGFR T790M variant is disproportionately concentrated among populations in the Southern Appalachian regions of Tennessee and Alabama. Evolutionary geneticists determined that the mutation originated among British and Irish settlers who migrated to North America during colonial times, with its frequency increasing following a genetic bottleneck approximately 200 years ago. Senior study author Dr. Pasi A. Jänne emphasized that, although current lung cancer screening largely relies on tobacco exposure, recognizing strong genetic risk factors opens opportunities for targeted low-dose computed tomography screening in non-smoking carriers.
Dana-Farber Cancer Institute’s Research Analyzes 3.3 Million Genomes
Supported by the National Institutes of Health through preclinical and clinical trials, researchers confirmed that the mutation has a strong specific association with lung cancer, showing no significant connection to 17 other common cancers evaluated in the dataset. Oncologists noted that while tobacco exposure remains the primary cause of lung cancer overall, non-smoking lung cancers are increasingly recognized as a significant global health concern. Several pharmaceutical companies, including AstraZeneca, are advancing targeted treatments such as tyrosine kinase inhibitors like Tagrisso for EGFR-mutated lung tumors that progress.
Co-senior author Dr. Alexander Gusev observed that the study demonstrates how a single inherited point mutation can have an extraordinarily strong impact on disease susceptibility. Medical professionals advise individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or with roots in Southern Appalachia to seek genetic counseling. The researchers also stressed that carrying the mutation does not mean a person will develop lung cancer, as environmental factors and secondary genetic changes influence whether malignant transformation occurs during a lifetime.
EGFR Gene’s Role in Controlling Cell Growth and Division
The research team plans to broaden observational efforts through the ongoing INHERIT Study to examine additional inherited EGFR variants across diverse racial and ethnic groups. Long-term monitoring will aim to identify environmental triggers and secondary genomic modifications that determine why some carriers develop tumors while others remain unaffected.
Comprehensive details on population genetics, risk assessments, and screening guidelines continue to be accessible via peer-reviewed medical repositories and institutional release portals. Future biomarker data will be presented at upcoming international oncology meetings to guide the evolution of screening protocols.