Rare Genetic Mutation Dramatically Increases Lung Cancer Risk, Study Finds

A rare inherited germline mutation, T790M in the epidermal growth factor receptor (EGFR) gene, has been identified as a significant risk factor for lung cancer, capable of increasing a person's risk by 62 times, even in individuals who do not smoke. For smokers carrying this mutation, the likelihood of developing the disease increases by 25 times.

While tobacco smoking remains the leading cause of lung cancer, escalating risk by four times in the general population, the study highlights that non-smokers are also vulnerable. Lung cancer is the second most common cancer in the U.S. and the leading cause of cancer death for both men and women, according to the American Cancer Society.

The EGFR gene plays a crucial role in cell growth and division. When mutated, it can promote the proliferation and spread of cancer cells. Researchers analyzed genetic data from over 3.37 million individuals via 23andMe and found the T790M mutation in approximately one in 15,850 people. The mutation showed a strong association only with lung cancer among 17 other conditions and cancers evaluated. Genetic analysis suggests the T790M mutation originated in Southern Appalachian populations in the U.S. approximately 200 to 225 years ago. The American Lung Association notes that EGFR mutation-positive lung cancer accounts for 10-15% of all lung cancers in the U.S., with a higher prevalence in Asian populations.

Experts suggest that current lung cancer screening methods, which primarily rely on assessing tobacco exposure, may need to evolve. Pasi Jänne, M.D., Ph.D., a lung cancer specialist at Dana-Farber Cancer Institute and a lead author of the study, stated that individuals with the T790M mutation could potentially benefit from enhanced screening and early detection strategies. Identifying cancers at an earlier, more treatable stage is a key goal.

Dr. Jänne also emphasized that the T790M mutation is not the sole determinant of lung cancer risk. Environmental factors and other genetic nuances may further influence an individual's lifetime risk of developing the disease. This research could pave the way for more personalized approaches to lung cancer screening and treatment, targeting individuals with specific genetic predispositions. Therapies such as AstraZeneca's Tagrisso and Johnson & Johnson's Rybrevant are already used to treat EGFR-mutated lung cancer, with new potential treatments like BlossomHill's BH-30643 also in development.