Frequency of EGFR and KRAS Mutations in Lung Adenocarcinomas in African Americans

Abstract

The detection of mutations in the epidermal growth factor receptor (EGFR) gene, which predict sensitivity to treatment with EGFR tyrosine kinase inhibitors, represents a major advance in the treatment of lung adenocarcinoma. KRAS mutations confer resistance to EGFR-tyrosine kinase inhibitors. The prevalence of these mutations in African American patients has not been thoroughly investigated. We collected formalin-fixed, paraffin-embedded material from resected lung adenocarcinomas from African American patients at three institutions for DNA extraction. The frequencies of EGFR exon 19 deletions, exon 21 L858R substitutions, and KRAS mutations in tumor specimens from African American patients were compared with data in white patients (n = 476). EGFR mutations were detected in 23 of the 121 specimens from African American patients (19%, 95% confidence interval [CI]: 13-27%), whereas KRAS mutations were found in 21 (17%, 95% CI: 12-25%). There was no significant difference between frequencies of EGFR mutations comparing African American and white patients, 19% versus 13% (61/476, 95% CI: 10-16%; p = 0.11). KRAS mutations were more likely among whites, 26% (125/476, 95% CI: 23-30%; p = 0.04). This is the largest study to date examining the frequency of mutations in lung adenocarcinomas in African Americans. Although KRAS mutations were somewhat less likely, there was no difference between the frequencies of EGFR mutations in African American patients, when compared with whites. These results suggest that all patients with advanced lung adenocarcinomas should undergo mutational analysis before initiation of therapy.