KRAS Mutation Status in Non-Small Cell Lung Cancer Distribution Across Occupational Categories.

Abstract

Lung cancer remains the leading cause of cancer-related deaths worldwide, with occupational carcinogen exposure contributing significantly to its etiology. However, the molecular mechanisms underlying this process remain largely unexplored. Does occupational exposure to specific carcinogens influence the molecular profile of metastatic non-small cell lung cancer (NSCLC)? A total of 302 patients with metastatic NSCLC without activating EGFR/ALK mutations were included, all of whom provided detailed occupational histories. Jobs were classified according to the International Standard Classification of Occupations (ISCO), an Adapted Classification (AC), and the carcinogenic exposure-based International Agency for Research on Cancer Classification (IARCC). Tumor biopsy specimens were analyzed by using next-generation sequencing. Comparisons were performed between each category and the rest of the cohort. Pairwise comparisons revealed significantly higher prevalence of KRAS mutations among cooks (AC; P = .035), whereas painters showed a trend toward significance (AC; P = .067). These associations were confirmed in multivariate analyses adjusted for sex and smoking status, with ORs of 5.81 (95% CI, 1.41-23.93) for cooks and 4.29 (95% CI, 1.03-17.91) for painters. Similarly, Personal Service Workers (ISCO) and Building and Related Trades Workers (ISCO) exhibited higher KRAS mutation prevalence (P = .003 and P = .027, respectively), which remained significant in multivariate analyses (OR of 5.46 [95% CI, 1.83-16.34] and 3.31 [95% CI, 1.18-9.26]). Conversely, lower KRAS mutation frequencies were observed among Information and Communications Technology Professionals (ISCO) (P = .031), office workers (AC; P = .002), and workers with low/no exposure (IARCC; P = .005). These associations were confirmed in multivariate models (OR of 0.34 [95% CI, 0.18-0.66] and 0.43 [95% CI, 0.25-0.75] for AC and IARCC). Finally, distinct distributions of KRAS mutation subtypes were found across occupations. Personal Service Workers (ISCO) were enriched for the G12C mutation (P = .012), painters for G12A (AC; P = .020), and chemically exposed workers for G12D (IARCC; P = .005). Our results suggest that occupational exposure is associated with distinct KRAS mutation prevalence in NSCLC, with different mutation patterns across job categories.