TY - JOUR
T1 - Ambient PM exposure and DNA methylation in tumor suppressor genes
T2 - A cross-sectional study
AU - Hou, Lifang
AU - Zhang, Xiao
AU - Tarantini, Letizia
AU - Nordio, Francesco
AU - Bonzini, Matteo
AU - Angelici, Laura
AU - Marinelli, Barbara
AU - Rizzo, Giovanna
AU - Cantone, Laura
AU - Apostoli, Pietro
AU - Bertazzi, Pier A.
AU - Baccarelli, Andrea
N1 - Funding Information:
This work was supported by the National Institute of Environmental Health Sciences (5P30ES000002), Environmental Protection Agency (R832416), Cassa di Rispamio delle Province Lombarde (CARIPLO) Foundation 2007-5469, the Italian Ministry of Scientific Research-Programs of Scientific Research of Relevant National Interest 2007-2S2HT8, Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine Northwestern University (P30 CA060553), and NIH award 1RC1ES018461-01.
PY - 2011/8/30
Y1 - 2011/8/30
N2 - 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
AB - 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
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U2 - 10.1186/1743-8977-8-25
DO - 10.1186/1743-8977-8-25
M3 - Article
C2 - 21878113
AN - SCOPUS:80052124957
SN - 1743-8977
VL - 8
JO - Particle and Fibre Toxicology
JF - Particle and Fibre Toxicology
M1 - 174325
ER -