WASHINGTON / RankWire.AI / – A previously uncommon inherited genetic change has been found to elevate an individual’s overall likelihood of developing lung cancer by about 25 times, and nearly 60 times among those who have never smoked, according to a study published in the journal Science. The research, a collaboration between scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute, analyzed anonymized genomic data from over 3.3 million people. The scientists identified the germline mutation, known as EGFR T790M, as one of the most significant inherited risk factors for lung cancer discovered so far.
This mutation takes place in the epidermal growth factor receptor gene, which controls cell growth and division within lung tissue. While somatic mutations in EGFR acquired during a person’s life are established drivers of non-small cell lung cancer, the T790M germline variant is inherited from birth and is present in every cell. According to data from the National Cancer Institute, the mutation appears in approximately 1 out of every 15,850 individuals in the U.S. Lead author Dr. Jaclyn LoPiccolo highlighted that carriers of this mutation have about a 62-fold increased risk of lung cancer in never-smokers, compared to roughly 11 times for those with a history of smoking.
Genealogical research revealed that the EGFR T790M variant is disproportionately common among populations in the Southern Appalachian regions of Tennessee and Alabama. Evolutionary geneticists traced the mutation back to British and Irish settlers who arrived in North America during colonial times. It became more prevalent following a genetic bottleneck around 200 years ago. Senior author Dr. Pasi A. Jänne emphasized that, although lung cancer screening currently focuses mainly on tobacco exposure, pinpointing strong genetic risk factors could lead to targeted low-dose computed tomography screening for carriers who do not smoke.
Dana-Farber Cancer Institute Research Analyzes Genomes of 3.3 Million Individuals
Supported by the National Institutes of Health, the study’s preclinical and clinical phases confirmed that the mutation has a specific strong association with lung cancer. No significant links were found between the mutation and 17 other common cancers evaluated within the dataset. Experts in oncology noted that while tobacco use remains the main cause of lung cancer overall, non-smoking-related lung cancers are becoming a growing concern worldwide. Several pharmaceutical companies, including AstraZeneca, are advancing the development of 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 extraordinarily strong effect on disease risk. Medical professionals advise individuals with multiple family members affected by lung cancer, unexplained lung nodules, or ancestral roots in Southern Appalachia to seek genetic counseling. The researchers stressed that carrying the mutation does not guarantee lung cancer development, as environmental factors and secondary genetic changes also influence whether malignancy occurs over a person’s lifetime.
EGFR Gene’s Role in Regulating Cell Growth and Division
The research team plans to extend observational efforts through the ongoing INHERIT Study, aiming to examine additional inherited EGFR variants across racially diverse populations. Long-term monitoring will focus on pinpointing specific environmental factors and secondary genetic alterations that determine why some carriers develop tumors while others do not exhibit symptoms.
In-depth results on population genetics, risk assessments, and screening protocols are accessible via peer-reviewed medical repositories and institutional publication portals. Future updates, including biomarker data, will be presented by clinical researchers at upcoming international oncology conferences to guide the refinement of screening guidelines.
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