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

Abstract

Up to 1% of patients with non-small cell lung cancer harbor germline epidermal growth factor receptor (<i>EGFR</i>) mutations, although they remain poorly described in unselected, noncancer populations. We sought to characterize the prevalence of germline <i>EGFR</i> mutations in Southeastern United States. We assessed the prevalence of <i>EGFR</i> mutations in unselected cohorts of individuals enrolled in the Duke CATHeterization GENetics, gnomAD, UK Biobank, and <i>All of Us</i> studies. We additionally performed comprehensive chart review for patients evaluated at the Duke Cancer Institute with germline <i>EGFR</i> mutations. We found the prevalence of germline <i>EGFR</i> T790M to be >1 in 3,000 individuals in the Duke catchment area. This prevalence was 7.5 times greater than the national <i>All of Us</i> 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 <i>All of Us</i> cohort. Twenty-eight individuals with suspected germline <i>EGFR</i> 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 <i>EGFR</i> mutations from both patients with lung cancer and unselected cohorts of individuals and presents evidence for increased prevalence of <i>EGFR</i> T790M mutations within the Southeastern United States. Given the high prevalence and documented hereditary risk of germline <i>EGFR</i> mutations, future studies investigating the role of familial testing and screening in these individuals is warranted.