title: Urinary benzene biomarkers and DNA methylation in Bulgarian petrochemical workers: study findings and comparison of linear and beta regression models.
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.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, United States of America. wes480@mail.harvard.edu
authors.forename: Wei Jie
authors.initials: WJ
authors.lastname: Seow
authors.forename: Angela Cecilia
authors.initials: AC
authors.lastname: Pesatori
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dimont
authors.forename: Peter B
authors.initials: PB
authors.lastname: Farmer
authors.forename: Benedetta
authors.initials: B
authors.lastname: Albetti
authors.forename: Adrienne S
authors.initials: AS
authors.lastname: Ettinger
authors.forename: Valentina
authors.initials: V
authors.lastname: Bollati
authors.forename: Claudia
authors.initials: C
authors.lastname: Bolognesi
authors.forename: Paola
authors.initials: P
authors.lastname: Roggieri
authors.forename: Teodor I
authors.initials: TI
authors.lastname: Panev
authors.forename: Tzveta
authors.initials: T
authors.lastname: Georgieva
authors.forename: Domenico Franco
authors.initials: DF
authors.lastname: Merlo
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D001554:Benzene / Q000633:toxicity*; D015415:Biomarkers / Q000652:urine*; D002031:Bulgaria; D002617:Chemical Industry; D019175:DNA Methylation; D006801:Humans; D008962:Models, Theoretical; D016273:Occupational Exposure
chemical_list: D015415:Biomarkers; D001554:Benzene