Prevalence and Clinical Characteristics of Germline Epidermal Growth Factor Receptor Mutations in the Southeastern...

Up to 1% of patients with non-small cell lung cancer harbor germline epidermal growth factor receptor (EGFR) mutations, although they remain poorly described in unselected, noncancer populations. We sought to characterize the prevalence of germline EGFR mutations in Southeastern United States.

We assessed the prevalence of EGFR mutations in unselected cohorts of individuals enrolled in the Duke CATHeterization GENetics, gnomAD, UK Biobank, and All of Us studies. We additionally performed comprehensive chart review for patients evaluated at the Duke Cancer Institute with germline EGFR mutations.

We found the prevalence of germline EGFR T790M to be >1 in 3,000 individuals in the Duke catchment area. This prevalence was 7.5 times greater than the national All of Us cohort, 3.7 times greater than the international gnomAD cohort, and 55.8 times greater than the UK Biobank cohort. The Southeastern region also contained the highest proportion of T790M carriers in the All of Us cohort. Twenty-eight individuals with suspected germline EGFR mutations were identified in our institutional cohort. The majority of these patients did not have a history of smoking, had multiple lung nodules at the time of diagnosis, and had a family history of cancer. Forty-five percent of patients had a diagnosis of a second primary malignancy.

Our analysis represents the largest study to date assessing the prevalence of germline EGFR mutations from both patients with lung cancer and unselected cohorts of individuals and presents evidence for increased prevalence of EGFR T790M mutations within the Southeastern United States. Given the high prevalence and documented hereditary risk of germline EGFR mutations, future studies investigating the role of familial testing and screening in these individuals is warranted.