Abstract B009: Analysis of the KRAS mutation spectrum in Black/African American and White/European lung adenocarcinoma patients, and its association with patient survival

Abstract Lung cancer is the most common cause of cancer-related deaths in the U.S. and its incidence and mortality rates in Black/African American (B/AA) men are 15% and 12% higher, respectively, than White/European (W/E) men. Lung adenocarcinoma is the most prevalent subtype of lung cancer in all ethnic/racial groups and is characterized by several driver mutations to genes in the RAS/RAF/MEK/ERK pathway, including KRAS. Alterations to these driver genes can vary in spectrum and frequency between ethnic/racial groups. This may influence outcomes depending on patients’ genetic backgrounds, resulting in differential response to therapy. We thus compared the frequency and spectra of mutations of the KRAS gene in B/AA and W/E patients using publicly available databases with lung adenocarcinoma (LUAD) sequencing (American Association for Cancer Research Project GENIE [Genomics Evidence Neoplasia Information Exchange], The Cancer Genome Atlas, and smaller datasets from a variety of publications). We also examined the association of the identified mutations with patient survival, with consideration of patient age, sex, and tobacco smoking history, where available. Using this information, we found that B/AA individuals had lower rates of KRAS mutations than W/E individuals. We also observed that across all patients with relevant data, those with a KRAS mutation tended to have poorer survival outcomes than those patients without. We are using information on the frequency and spectrum of KRAS mutations to develop models for lung adenocarcinoma development in B/AA patients, among others by generating isogenic cell lines carrying different KRAS mutations. Further investigations of public and published LUAD datasets are ongoing. Using the correct cell and gene models constitute a key approach to address health disparities in LUAD research and treatment. Citation Format: Daniel J Mullen, Sofia Lugo, Pablo E. Puente, Kweku Ofosu-Asante, Justin K. Mensah-Mamfo, Kyle R. Phillips, Yong Huang, Nazarius S. Lamango, Ite A. Offringa. Analysis of the KRAS mutation spectrum in Black/African American and White/European lung adenocarcinoma patients, and its association with patient survival [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr B009.