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Updated: Sep 20, 2026

Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Germline EGFR T790M mutation and lung cancer risk
Jaclyn LoPiccolo1,2, Steven Micheletti3, Jing Shi3
1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Abstract:
Most lung cancers are tobacco related, with genetic factors influencing smoking behavior identified through genome-wide association studies. However, inherited risk in familial and non-smoking-related lung cancers, including risk in carriers of EGFR T790M, remains poorly understood. Here, in more than 3.3 million individuals, the EGFR T790M germline variant is significantly associated with lung cancer risk, with no increased risk for 17 other cancers and no interaction with polygenic risk. This risk exceeds that conferred by smoking and is several-fold higher in never-smokers. Global geographic and ancestry analyses show higher T790M prevalence in the US than in British- and Irish-descendant populations, reflecting a Southern Appalachian founder event about 200 to 225 years ago, increasing regional prevalence and affecting those of British, Irish, and African descent. Recognition of high-risk carriers may inform targeted genetic testing and screening strategies.
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