title: Ambient PM exposure and DNA methylation in tumor suppressor genes: a cross-sectional study.
abstract: Exposure to ambient air particles matter (PM) has been associated with increased risk of lung cancer. Aberrant tumor suppressor gene promoter methylation has emerged as a promising biomarker for cancers, including lung cancer. Whether exposure to PM is associated with peripheral blood leukocyte (PBL) DNA methylation in tumor suppressor genes has not been evaluated. In 63 male healthy steel workers with well-characterized exposure to metal-rich particles nearby Brescia, Italy, we evaluated whether exposure to PM and metal components was associated with PBL DNA methylation in 4 tumor suppressor genes (i.e., APC, p16, p53 and RASSF1A). Blood samples were obtained on the 1st (baseline) and 4th day (post-exposure) of the same work week and DNA methylation was measured using pyrosequencing. A linear mixed model was used to examine the correlations of the exposure with promoter methylation levels. Mean promoter DNA methylation levels of APC or p16 were significantly higher in post-exposure samples compared to that in baseline samples (p-values = 0.005 for APC, and p-value = 0.006 for p16). By contrast, the mean levels of p53 or RASSF1A promoter methylation was decreased in post-exposure samples compared to that in baseline samples (p-value = 0.015 for p53; and p-value < 0.001 for RASSF1A). In post-exposure samples, APC methylation was positively associated with PM10 (β = 0.27, 95% CI: 0.13-0.40), and PM1 (β = 0.23, 95% CI: 0.09-0.38). In summary, ambient PM exposure was associated with PBL DNA methylation levels of tumor suppressor genes of APC, p16, p53 and RASSF1A, suggesting that such methylation alterations may reflect processes related to PM-induced lung carcinogenesis.
authors: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, 680 N, Lakeshore Drive, Chicago, 60611, USA. l-hou@northwestern.edu
authors: Lifang
authors: L
authors: Hou
authors: Xiao
authors: X
authors: Zhang
authors: Letizia
authors: L
authors: Tarantini
authors: Francesco
authors: F
authors: Nordio
authors: Matteo
authors: M
authors: Bonzini
authors: Laura
authors: L
authors: Angelici
authors: Barbara
authors: B
authors: Marinelli
authors: Giovanna
authors: G
authors: Rizzo
authors: Laura
authors: L
authors: Cantone
authors: Pietro
authors: P
authors: Apostoli
authors: Pier Alberto
authors: PA
authors: Bertazzi
authors: Andrea
authors: A
authors: Baccarelli
mesh_terms: D000395:Air Pollutants, Occupational / Q000032:analysis / Q000633:toxicity*; D003430:Cross-Sectional Studies; D019175:DNA Methylation / Q000187:drug effects*; D003627:Data Interpretation, Statistical; D006801:Humans; D007558:Italy; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008669:Metallurgy; D008670:Metals / Q000032:analysis / Q000633:toxicity; D016273:Occupational Exposure / Q000009:adverse effects / Q000032:analysis; D010316:Particle Size; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D000395:Air Pollutants, Occupational; D008670:Metals; D052638:Particulate Matter; D025521:Tumor Suppressor Proteins