Abstract
Lung cancer remains as the leading cause of cancer mortality worldwide. However, while current evidence suggests the existence of genomic differences between populations, indicating different risk factors associated with population-level genetic backgrounds, most studies have concentrated on populations of European ancestry, and more research is needed on non-European populations. We analyzed whole-exome sequencing data from 25 Mexican lung adenocarcinoma patients and compared them with a TCGA-PanCancer cohort enriched with patients of European ancestry as reference. Clinically relevant germline variants in cancer susceptibility genes are more frequent in our cohort (32% vs. 6.4%) than in the reference. Several mutational signatures (SBS32, SBS85, SBS12, SBS19) occurred at significantly higher frequencies in the Mexican cohort compared to the reference (p < 0.0001). Interestingly, the smoking-associated signature SBS4, present in 67.6% of smokers in the reference cohort, was absent in smoking Mexican patients (p < 0.01656). Somatic variant frequencies in SLC36A4 (20%; p < 0.00002), AP1S1 (8%; p < 0.00002), and TP53 (16%; p = 0.00005) showed significant differences from the European reference cohort. We demonstrate that all these observed biases were independent of the sample size. This study uncovers distinct genomic biases in lung cancer carcinogenesis in this population, compared to a European ancestry reference population, suggesting implications for precision medicine strategies in Latin American populations.