O-193 THE SAFECHROM PROJECT - CIRCULATING LUNG-CANCER-RELATED NON-CODING RNAS ARE ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO HEXAVALENT CHROMIUM

Hexavalent chromium, Cr(VI), is classified as a Group 1 human carcinogen and causes lung cancer. This study was to investigate associations between occupational exposure to Cr(VI) and lung cancer-related non-coding RNAs.The study included 111 Cr(VI) exposed workers and 72 controls in Sweden, 91.4\smokers. Cr concentration in red blood cells (RBC-Cr) was measured. MicroRNA (miRNA) and long non-coding RNA (lncRNA) were extracted from plasma followed by DNAse treatment, cDNA synthesis, and qPCR using target-specific assays for four miRNAs (miR-142-3p, miR-15b-5p, miR-3940-5p, miR-451a), and three lncRNAs (H19, MALAT1, NORAD).Median RBC-Cr concentrations were significantly higher in the exposed group (0.73 µg/L, 5-95\.51-2.33) compared with controls (0.53 µg/L, 0.42-0.72). Plasma relative expression levels of all miRNAs, MALAT1 and NORAD were significantly lower in the exposed workers compared with controls. In the exposed group, significant negative correlations (rS=-0.19 - -0.27) were found between RBC-Cr and miR-142-3p, miR-15b-5p, miR-451a and NORAD. NORAD correlated with miR-142-3p (rS=0.34) and miR-15b-5p (rS=0.28). In multivariate regression models adjusting for confounders, expression of the miRNAs, MALAT1 and NORAD was still significantly lower in the exposed group compared with controls, and the expression decreased with increasing RBC-Cr.Cr(VI) exposure was associated in a dose-response manner with differential expression of circulating non-coding RNAs in exposed workers, which suggests non-coding RNAs as potential toxicological biomarkers for Cr(VI). Relations between miRNAs and lncRNAs suggest that they participate in the same lncRNA-miRNA-mRNA regulatory axes, which may play important roles in Cr(VI) carcinogenesis.Occupational Cr(VI) exposure may impact circulating lung-cancer-related non-coding RNAs expression.