Additional impact of genetic ancestry over race/ethnicity to prevalence of KRAS mutations and allele-specific subtypes in non-small cell lung cancer

The KRAS mutation is the most common oncogenic driver in patients with non-small cell lung cancer (NSCLC). However, a detailed understanding of how self-reported race and/or ethnicity (SIRE), genetically inferred ancestry (GIA), and their interaction affect KRAS mutation is largely unknown. Here, we investigated the associations between SIRE, quantitative GIA, and KRAS mutation and its allele-specific subtypes in a multi-ethnic cohort of 3,918 patients from the Boston Lung Cancer Survival cohort and the Chinese OrigiMed cohort with an independent validation cohort of 1,450 patients with NSCLC. This comprehensive analysis included detailed covariates such as age at diagnosis, sex, clinical stage, cancer histology, and smoking status. We report that SIRE is significantly associated with KRAS mutations, modified by sex, with SIRE-Asian patients showing lower rates of KRAS mutation, transversion substitution, and the allele-specific subtype KRAS