Genetic and epigenetic effects in a population of underground miners with coal workers Pneumoconiosis

Coal Workers Pneumoconiosis (CWP) is a respiratory occupational disease caused by chronic exposure to breathable mine dust which is characterized by an inflammatory reaction and a subsequent progressive massive fibrosis. The disease is irreversible and incurable; therefore, early diagnosis or prediction may become useful to control CWP. Oxidative stress is known to play an important rolein pathogenesis.Oxidative DNA damageis repaired by the Base Excision Repair (BER) pathway; therefore,genetic variations in BER pathway enzymes may confer differential risk in CWP. On the other hand, as has been shown for other environmental pollutants DNA methylation may represent an interface between exposure and disease. Biomarkers of exposure, effect and susceptibility were assessed in order to evaluate oxidative stress and methylation changes associated with the disease and the influence ofOGG1and XRCC1polymorphisms in CWP development. A group of 474 underground coal miners were selected to participate in this cross-sectional study. This population was subdivided into two groups of healthy and CWP miners. We show that underground miners who develop pneumoconiosis have a higher level of the oxidative stress marker 8-OHdG in white blood cells, and that this oxidative DNA damage was associated withXRCC1194Trp allele. In addition, leukocytes from CWP cases are differentially methylated at two immune-related loci when compared with control miners, as assessed by bisulfite pyrosequencing. Information regarding genetic, epigenetic and exposure conditions will contribute to the better understanding of disease aetiology in a population.