Author(s): Seow WJ, Pesatori AC, Dimont E, Farmer PB, Albetti B,
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Abstract Chronic occupational exposure to benzene is associated with an increased risk of hematological malignancies such as acute myeloid leukemia (AML), but the underlying mechanisms are still unclear. The main objective of this study was to investigate the association between benzene exposure and DNA methylation, both in repeated elements and candidate genes, in a population of 158 Bulgarian petrochemical workers and 50 unexposed office workers. Exposure assessment included personal monitoring of airborne benzene at work and urinary biomarkers of benzene metabolism (S-phenylmercapturic acid [SPMA] and trans,trans-muconic acid [t,t-MA]) at the end of the work-shift. The median levels of airborne benzene, SPMA and t,t-MA in workers were 0.46 ppm, 15.5 µg/L and 711 µg/L respectively, and exposure levels were significantly lower in the controls. Repeated-element DNA methylation was measured in Alu and LINE-1, and gene-specific methylation in MAGE and p15. DNA methylation levels were not significantly different between exposed workers and controls (P>0.05). Both ordinary least squares (OLS) and beta-regression models were used to estimate benzene-methylation associations. Beta-regression showed better model specification, as reflected in improved coefficient of determination (pseudo R(2)) and Akaike's information criterion (AIC). In beta-regression, we found statistically significant reductions in LINE-1 (-0.15\%, P<0.01) and p15 (-0.096\%, P<0.01) mean methylation levels with each interquartile range (IQR) increase in SPMA. This study showed statistically significant but weak associations of LINE-1 and p15 hypomethylation with SPMA in Bulgarian petrochemical workers. We showed that beta-regression is more appropriate than OLS regression for fitting methylation data.
This article was published in PLoS One
and referenced in Journal of Molecular Biomarkers & Diagnosis