Scientists at the Dana-Farber Cancer Institute and the 23andMe Research Institute have discovered a very rare genetic mutation in the Epidermal Growth Factor Receptor gene which increases a person's chance of developing lung cancer by 25 times. Scientists conducted their analysis using the anonymized, aggregated genomic data of over 3.3 million research participants who agreed to their data being used at 23andMe. The results showed that the EGFR T790M mutation led to one of the highest risks for lung cancer.
Compared to those without the EGFR T790M variant, never-smokers harboring this genetic variant were 60 times more likely to suffer from lung cancer. In smokers, on the other hand, those with the EGFR T790M variant were about 10 times more likely to develop the disease compared to those without the mutation. The scientists clarified that the disparity in risk did not indicate that smoking is protective against lung cancer.
"Today, lung cancer screening is almost completely determined by smoking history," said Jaclyn LoPiccolo, M.D., Ph.D., an attending physician and lung cancer researcher at the Dana-Farber Cancer Institute and a co-author of the study. The study results suggest that genetics can play a role in screening in the future," she added.
The EGFR T790M mutation was first discovered in 2005 among a European family having many cases of lung cancer and has also been reported in other families that have unusually high incidence of lung cancer. Scientists utilized the extensive database of genetics to see if the mutation was prevalent among those individuals suffering from lung cancer, as well as non-smokers.
They found that the mutation was not related to any of the other 17 common cancers studied, which implies that the mutation might affect mainly lung cancer patients. In addition, the study estimated that the mutation is observed in around 1 out of 15,000 people in the U.S., while the frequency of occurrence can even go up to 1 out of 2,000 people in some parts of the southeastern United States.
"Should further studies confirm the effectiveness of this approach, patients who have the EGFR T790M gene mutation would be tested for it and offered personalized CT screenings in order to detect lung cancer at its most treatable stage," explained LoPiccolo.
Individuals with multiple relatives affected by lung cancer, multiple lung nodules, multifocal lung cancers, or those who hail from regions in the southeastern part of the country where this mutation is prevalent are advised to seek genetic counseling according to the recommendations of the researchers.
In future investigations, the researchers intend to study why some individuals with this EGFR T790M mutation contract lung cancer while others do not, why the mutation increases the chances of developing lung cancer yet not any other common type of cancer, and how environmental factors and other gene mutations interact with the mutation to increase the likelihood of developing lung cancer.
In fact, the identification of genetic mutations in EGFR that increase one's chances of developing lung cancer indicates the possibility of using genetic screening in the future. Genetic risk assessment can be another source of information to find people who need to undergo screening for lung cancer.
The Dana-Farber Cancer Institute is an institute that does research and treatment for cancer located in Boston. Researchers at the Dana-Farber Cancer Institute who were part of the study include Jaclyn LoPiccolo, M.D., Ph.D. Pasi A. Janne, M.D., Ph.D.; and Alexander Gusev, Ph.D. The study conducted research to establish a correlation between the inherited EGFR T790M mutation and lung cancer based on genetic information and lung cancer data of millions of research-consented participants.
Financial support for the study came from foundations and institutes like LUNGevity Foundation, Elaine & Gerald Schuster Fund for Lung Cancer Research, National Institutes of Health, American Cancer Society, Chen-Huang Center for EGFR-Mutant Lung Cancers, GO2 for Lung Cancer, and many others.
