A new Phase I study is exploring whether an investigational cancer vaccine, BNT116, can be combined with immunotherapy and chemotherapy before surgery to help the immune system recognize and attack NSCLC.
A study by investigators at Dana-Farber Cancer Institute and 23andMe Research Institute analyzed genetic and health data from more than 3 million people and report that an inherited variant (T790M) in the epidermal growth factor receptor (EGFR) gene is strongly associated with lung cancer risk.
Key Takeaways
The authors traced the history of the EGFR T790M mutation and found that the variant became enriched in the United States through a founder event in the Southern Appalachian region approximately 200 years ago. These insights reinforce the contribution of EGFR T790M to inherited lung cancer risk and may help to identify individuals who could benefit from genetic testing and lung cancer screening approaches. The study was published in Science.
Importantly, this is an inherited (germline) EGFR T790M variant, which is different from the T790M mutation that can develop within a lung tumor as a mechanism of resistance to EGFR-targeted therapies. Having the inherited variant does not mean that someone will necessarily develop lung cancer. The inherited EGFR T790M variant was first reported in 2005 in a European family with multiple cases of lung cancer. Since then, it has been identified in additional families with unusually high rates of lung cancer.
The study included data from the Lung Cancer Genetics Study (LCGS), funded by the Susan Wojcicki Foundation and powered by the 23andMe Research Institute, in collaboration with more than 20 lung cancer advocacy organizations, including The Happy Lungs Project.
Results
- Among 3,372,531 individuals, the germline EGFR T790M variant was found in approximately 1 in 15,850 people and was strongly associated with lung cancer.
- No significant associations were observed with the 17 non-lung cancer types or noncancerous pulmonary conditions evaluated. T
- he association was largely independent of broader genetic susceptibility to lung cancer.
- The effect was stronger among people who had never smoked than among those who had smoked.
- The variant was more common in the United States, occurring in approximately 1 in 8,920 people, compared with populations of British and Irish descent.
- Fine-scale geographic and ancestry analyses identified a founder effect in the Southern Appalachian region approximately 200–225 years ago, where the carrier frequency was approximately 1 in 2,078.
- The variant subsequently expanded into additional populations, including those with African and Indigenous American ancestry.
What Could This Mean for Screening?
Current lung cancer screening recommendations are largely based on age and smoking history. These findings raise the possibility that inherited genetic risk could eventually become another factor in identifying people who may benefit from screening. However, more research is needed to determine how people who carry EGFR T790M should be monitored and whether earlier or more frequent screening could improve outcomes.
People with multiple lung nodules, multifocal lung cancer, several family members with lung cancer, or ancestry associated with a higher prevalence of the variant may want to discuss their personal and family history with a genetic counselor. A genetic counselor can help assess personal and family history and determine whether genetic testing may be appropriate.
