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.

Urinary benzene biomarkers and DNA methylation in Bulgarian petrochemical workers : study findings and comparison of linear and beta regression models / W.J. Seow, A.C. Pesatori, E. Dimont, P.B. Farmer, B. Albetti, A.S. Ettinger, V. Bollati, C. Bolognesi, P. Roggieri, T.I. Panev, T. Georgieva, D.F. Merlo, P.A. Bertazzi, A. Baccarelli. - In: PLOS ONE. - ISSN 1932-6203. - 7:12(2012), pp. e50471.1-e50471.8. [10.1371/journal.pone.0050471]

Urinary benzene biomarkers and DNA methylation in Bulgarian petrochemical workers : study findings and comparison of linear and beta regression models

A.C. Pesatori
Secondo
;
B. Albetti;V. Bollati;P.A. Bertazzi
Penultimo
;
A. Baccarelli
Ultimo
2012

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.
Chemical Industry ; DNA Methylation ; Occupational Exposure ; Benzene ; Biological Markers ; Bulgaria ; Humans ; Models, Theoretical
Settore MED/44 - Medicina del Lavoro
Article (author)
File in questo prodotto:
File Dimensione Formato  
pone.0050471.pdf

accesso aperto

Tipologia: Publisher's version/PDF
Dimensione 307.53 kB
Formato Adobe PDF
307.53 kB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/226910
Citazioni
  • ???jsp.display-item.citation.pmc??? 20
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 40
social impact