A systematic review of genetic ancestry as a risk factor for incidence of non-small cell lung cancer in the US

Abstract

Background: Non-Small Cell Lung Cancer (NSCLC), the leading cause of cancer-related death in the United States, is the most diagnosed form of lung cancer. While lung cancer incidence has steadily declined over the last decade, disparities in incidence and mortality rates persist among African American (AA), Caucasian American (CA), and Hispanic American (HA) populations. Researchers continue to explore how genetic ancestry may influence differential outcomes in lung cancer risk and development. The purpose of this evaluation is to highlight experimental research that investigates the differential impact of genetic mutations and ancestry on NSCLC incidence. Methods: This systematic review was conducted using PubMed and Google Scholar search engines. The following key search terms were used to select articles published between 2011 and 2022: "African/European/Latin American Ancestry NSCLC"; "Racial Disparities NSCLC"; "Genetic Mutations NSCLC"; "NSCLC Biomarkers"; "African Americans/Hispanic Americans/Caucasian Americans NSCLC incidence." Systematic reviews, meta-analyses, and studies outside of the US were excluded. A total of 195 articles were initially identified and after excluding 156 which did not meet eligibility criteria, 38 were included in this investigation. Results: Studies included in this analysis focused on racial/ethnic disparities in the following common genetic mutations observed in NSCLC: KRAS, EGFR, TP53, PIK3CA, ALK Translocations, ROS-1 Rearrangements, STK11, MET, and BRAF. Results across studies varied with respect to absolute differential expression. No significant differences in frequencies of specific genetic mutational profiles were noted between racial/ethnic groups. However, for HAs, lower mutational frequencies in KRAS and STK11 genes were observed. In genetic ancestry level analyses, multiple studies suggest that African ancestry is associated with a higher frequency of EGFR mutations. Conversely, Latin ancestry is associated with TP53 mutations. At the genomic level, several novel predisposing variants associated with African ancestry and increased risk of NSCLC were discovered. Family history among all racial/ethnic groups was also considered a risk factor for NSCLC. Conclusion: Results from racially and ethnically diverse studies can elucidate driving factors that may increase susceptibility and subsequent lung cancer risk across different racial/ethnic groups. Identification of biomarkers that can be used as diagnostic, prognostic, and therapeutic tools may help improve lung cancer survival among high-risk populations.

Keywords: biomarkers; genetic ancestry; genetics; lung cancer; non-small cell lung cancer; racial disparities; risk factors.