WASHINGTON / RankWire.AI / – Researchers have uncovered a rare inherited genetic mutation that can elevate an individual’s likelihood of developing lung cancer by approximately 25 times overall and by about 60 times among non-smokers, according to a pivotal study 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 information from over 3.3 million people. The team identified the germline variant, known as EGFR T790M, as one of the most significant inherited risk factors for lung cancer discovered so far.
This mutation is found in the epidermal growth factor receptor gene, which plays a key role in controlling cell growth and division within lung tissue. While somatic mutations in EGFR 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 about 1 in every 15,850 individuals in the United States. Lead researcher Dr. Jaclyn LoPiccolo remarked that carrying this variant increases lung cancer risk approximately 62 times among never-smokers, versus roughly 11 times in those with a history of smoking.
Genetic tracing revealed that the EGFR T790M variant is disproportionately concentrated within populations of Southern Appalachia, particularly across Tennessee and Alabama. Evolutionary geneticists determined that this mutation originated among British and Irish settlers who immigrated to North America during the colonial period, with its prevalence increasing following a genetic bottleneck approximately 200 years ago. Senior study author Dr. Pasi A. Jänne emphasized that although current lung cancer screening primarily targets tobacco exposure, the identification of strong genetic risk factors paves the way for targeted low-dose computed tomography screening in non-smoking carriers.
Gene Variants Might Elevate Lung Cancer Risk by as Much as 60 Times in Non-Smokers
Supported by the National Institutes of Health, preclinical and clinical trials confirmed that this mutation shows a significant specific association with lung cancer, with no notable links to 17 other common cancers examined. Oncologists highlight that, although tobacco exposure remains the primary overall cause of lung cancer, the increasing incidence of lung cancer among non-smokers has become a critical global health concern. Pharmaceutical companies like AstraZeneca continue to develop targeted tyrosine kinase inhibitors such as Tagrisso to treat EGFR-mutated lung tumors when they progress.
Co-senior author Dr. Alexander Gusev noted that this research illustrates how a single inherited point mutation can exert a profoundly powerful influence on disease susceptibility. Medical experts advise that individuals with multiple family members affected by lung cancer, unexplained multifocal lung nodules, or ancestral ties to Southern Appalachia should seek genetic counseling. The researchers stress that possessing the mutation does not necessarily result in a lung cancer diagnosis, as environmental factors and additional genetic modifications can influence whether malignancy develops over time.
Multicenter Study Group Examines Genetic Data from Over Three Million Participants
The research coalition plans to expand observational studies through the ongoing INHERIT Study, aiming to assess other inherited EGFR variants across diverse racial groups. Long-term tracking will focus on identifying specific environmental triggers and secondary genetic changes that determine why some carriers develop tumors while others remain unaffected.
Findings regarding population genetics, risk assessments, and screening protocols remain accessible through peer-reviewed medical repositories and institutional release portals. Researchers will present updated biomarker data at upcoming international oncology conferences to inform future screening guidelines.