Abstract Rationale Lung cancer (LC) remains one of the leading causes of cancer-related mortality in the United States. Despite major advances in molecular profiling, Hispanic individuals remain underrepresented in genomic studies, limiting the understanding of population-specific alterations. Identifying genomic patterns in this population is essential for improving biomarker-driven therapy and clinical trial inclusion. This study characterizes the most prevalent genomic alterations in Puerto Rican (PR) veterans with LC and compares their frequency with previously reported Hispanic cohorts. Methods Retrospective observational cohort study included PR veterans diagnosed with LC between June 2019 and December 2024. Genomic profiling of tumors was performed using FoundationOne CDx next-generation sequencing. The clinical and histological data were analyzed using descriptive statistics. The results were compared with previously published PR civilian cohorts to explore population-specific differences. Results A total of 124 patients were analyzed: 118 (95.2%) had non-small cell lung cancer (NSCLC). Adenocarcinoma predominated. Compared with the previously published PR civilian cohort on NSCLC (Zheng et al.), PR veterans showed a significantly lower EGFR alteration rate (7.6% vs. 24.0%, p = 0.0001) Table 1. The other alterations, including KRAS (19.5% vs. 18.7%) and MET amplification (5.9% vs. 10.2%), were not significantly different. The incidence of TP53 (66.7%) and CDKN2A/B (16.9%) frequency was not reported by Zeng et al but was notably high. Conclusion We present the first genomic analysis of PR veterans with lung cancer, revealing a distinct genomic alteration landscape compared with previously reported Hispanic cohorts. The lower EGFR frequency and higher prevalence of TP53 and KRAS genomic alterations may reflect a unique demographic or environmental characteristic within tumor biology in the veteran population. The predominance of TP53 alterations given its association to genomic instability commonly described in exposure-related lung carcinogenesis. These findings contribute essential data toward equitable precision oncology and highlight the need for better understanding of population-specific genomic alteration patterns to improve equitable access to biomarker testing, guide therapeutic development, and strengthen the foundation for inclusive precision oncology. This abstract is funded by: None
Paredes-Gonzalez et al. (Fri,) studied this question.