RESUMEN
OBJECTIVE: Occupational exposure to welding fumes is linked to a higher risk of cardiovascular disease; however, the threshold exposure level is unknown. Here, we aimed to identify changes in proteins associated with cardiovascular disease in relation to exposure to welding fumes. METHODS: Data were obtained from two timepoints six years apart for 338 non-smoking men (171 welders, 167 controls); of these, 174 (78 welders, 96 controls) had measurements available at both timepoints. Exposure was measured as personal respirable dust (adjusted for personal protective equipment), welding years, and cumulative exposure. Proximity extension assays were used to measure a panel of 92 proteins involved in cardiovascular processes in serum samples. Linear mixed models were used for longitudinal analysis. The biological functions and diseases related to the identified proteins were explored using the Ingenuity Pathway Analysis software. RESULTS: At both timepoints, the median respirable dust exposure was 0.7 mg/m3 for the welders. Seven proteins were differentially abundant between the welders and controls and increased incrementally with respirable dust: FGF23, CEACAM8, CD40L, PGF, CXCL1, CD84, and HO1. CD84 was significant after adjusting for multiple comparisons. These proteins have been linked to disorders of blood pressure, damage related to clogged blood vessels, and chronic inflammatory disorders. CONCLUSION: Exposure to mild steel welding fumes below current occupational exposure limits for respirable particles and welding fumes in Europe and the US (1-5 mg/m3) was associated with changes in the abundance of proteins related to cardiovascular disease. Further research should evaluate the utility of these proteins as prospective biomarkers of occupational cardiovascular disease.
Asunto(s)
Contaminantes Ocupacionales del Aire , Enfermedades Cardiovasculares , Polvo , Exposición Profesional , Soldadura , Humanos , Masculino , Exposición Profesional/efectos adversos , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/sangre , Adulto , Persona de Mediana Edad , Contaminantes Ocupacionales del Aire/efectos adversos , Contaminantes Ocupacionales del Aire/análisis , Estudios Longitudinales , Polvo/análisis , Exposición por Inhalación/efectos adversos , Exposición por Inhalación/análisis , Enfermedades Profesionales/sangre , Enfermedades Profesionales/etiología , Enfermedades Profesionales/epidemiología , Estudios de Casos y Controles , Biomarcadores/sangreRESUMEN
OBJECTIVE: This study tested for an association between early cancer-related biomarkers and low-to-moderate exposure to fumes from welding mild steel. METHODS: Male, non-smoking participants from southern Sweden were recruited and examined (N=338, 171 welders and 167 controls); of these, 78 welders and 96 controls were examined on two occasions six years apart. Exposure to welding fumes was evaluated by measuring respirable dust, welding years, and cumulative exposure. DNA methylation of CpG sites within the cancer-related genes AHRR, F2RL3, and B3GNTL1 was measured by pyrosequencing and relative mitochondrial DNA copy number and telomere length were measured by qPCR in whole-blood samples. Multivariate models were used for longitudinal analysis. RESULTS: Median exposure to respirable dust was 0.7 mg/m3 at both timepoints, adjusted for use of personal protective equipment. Compared with controls, welders showed a significant decrease over time in DNA methylation of B3GNTL1 CpG1 and CpG4 [adjusted for age, body mass index, and smoking: ß=-0.66, standard error (SE)=0.28; ß=-0.48, SE=0.24, respectively]. In addition, exposure to respirable dust and cumulative exposure was associated with a decrease in methylation of F2RL3 CpG2 among all welders (adjusted ß=-0.67, SE=0.23 and ß=-0.03, SE=0.02, respectively). No significant associations were found for AHRR, mitochondrial DNA copy number, or telomere length. CONCLUSION: Low-to-moderate exposure to welding fumes was associated with a small effect on selected early epigenetic biomarkers of cancer. The direction of the methylation pattern (lower methylation of specific CpG sites) indicates early lung cancer-related changes associated with mild steel welding.