Researchers have identified a very rare genetic variant associated with a significantly increased risk of developing lung cancer, particularly among individuals who have never smoked according to STAT. The findings were reported in the journal Science on a Thursday.
Rare EGFR Variant and Heightened Lung Cancer Risk
The variant in question is known as T790M, which is a version of the EGFR gene that typically helps regulate how cells grow and divide, according to the Boston Globe. For never-smokers, carriers of the T790M variant were found to be some 60 times more likely to develop lung cancer, while the variant raised the risk by 10-fold among smokers. Experts noted that this does not suggest smoking is protective, but rather that smokers already carry a much higher baseline risk of lung cancer regardless of their T790M status. In the United States, the variant is far more common among people in Southern Appalachia than in other regions.
Insights from Large Genetic Datasets
To determine the strength of the association between the variant and lung cancer and to understand how common it is, a research group led by investigators at Boston’s Dana-Farber Cancer Institute analyzed data from millions of people who had their DNA examined by 23andMe and agreed to have their information open to scientific studies.
Jaclyn LoPiccolo, a thoracic oncologist at Dana-Farber and the lead author of the study, stated that the findings demonstrate how inherited genetic susceptibility can produce profound lung cancer risk in some people. For comparison, well-known BRCA mutations increase a person’s risk of breast cancer by five to eight times, though researchers cautioned against drawing direct comparisons given differences in study design and that T790M is being newly examined. In a surprise to the research team, the variant was not associated with an increased likelihood of more than a dozen other tumor types considered in the analysis.
Implications for Screening and Treatment
Experts noted that while the variant likely plays a role in only a small portion of never-smoker lung cancer cases, the research provides further evidence that these tumors can be tied to distinct risk factors. Deborah Caswell, a lung cancer biologist at University College London who was not involved with the study, remarked that even though the variant is very rare, the amount of increased risk it confers is huge.
The discovery highlights how turning to large datasets with health information from millions of people can yield narrow but crucial discoveries. Researchers indicated that these distinct risk factors may ultimately require thinking differently about screening programs and treatment strategies for patients who develop lung cancer without a history of smoking. The study’s authors are currently investigating the absolute risk carried by T790M carriers and are studying why inheriting the variant is more likely to lead to lung cancer, as T790M does not appear to directly cause the disease on its own.