title: Altered methylation in tandem repeat element and elemental component levels in inhalable air particles.
abstract: Exposure to particulate matter (PM) has been associated with lung cancer risk in epidemiology investigations. Elemental components of PM have been suggested to have critical roles in PM toxicity, but the molecular mechanisms underlying their association with cancer risks remain poorly understood. DNA methylation has emerged as a promising biomarker for environmental-related diseases, including lung cancer. In this study, we evaluated the effects of PM elemental components on methylation of three tandem repeats in a highly exposed population in Beijing, China. The Beijing Truck Driver Air Pollution Study was conducted shortly before the 2008 Beijing Olympic Games (June 15-July 27, 2008) and included 60 truck drivers and 60 office workers. On two days separated by 1-2 weeks, we measured blood DNA methylation of SATα, NBL2, D4Z4, and personal exposure to eight elemental components in PM2.5 , including aluminum (Al), silicon (Si), sulfur (S), potassium (K), calcium (Ca) titanium (Ti), iron (Fe), and zinc (Zn). We estimated the associations of individual elemental component with each tandem-repeat methylation in generalized estimating equations (GEE) models adjusted for PM2.5 mass and other covariates. Out of the eight examined elements, NBL2 methylation was positively associated with concentrations of Si [0.121, 95% confidence interval (CI): 0.030; 0.212, False Discovery Rate (FDR) = 0.047] and Ca (0.065, 95%CI: 0.014; 0.115, FDR = 0.047) in truck drivers. In office workers, SATα methylation was positively associated with concentrations of S (0.115, 95% CI: 0.034; 0.196, FDR = 0.042). PM-associated differences in blood tandem-repeat methylation may help detect biological effects of the exposure and identify individuals who may eventually experience higher lung cancer risk.
authors.affiliation: Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois; The Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.forename: Sheng
authors.initials: S
authors.lastname: Wang
authors.forename: Chang
authors.initials: C
authors.lastname: Dou
authors.forename: Liqiong
authors.initials: L
authors.lastname: Guo
authors.forename: Hyang-Min
authors.initials: HM
authors.lastname: Byun
authors.forename: Valeria
authors.initials: V
authors.lastname: Motta
authors.forename: John
authors.initials: J
authors.lastname: McCracken
authors.forename: Anaité
authors.initials: A
authors.lastname: Díaz
authors.forename: Choong-Min
authors.initials: CM
authors.lastname: Kang
authors.forename: Petros
authors.initials: P
authors.lastname: Koutrakis
authors.forename: Pier Alberto
authors.initials: PA
authors.lastname: Bertazzi
authors.forename: Jingyun
authors.initials: J
authors.lastname: Li
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000633:toxicity*; D016902:Air Pollution, Indoor / Q000032:analysis; D015415:Biomarkers / Q000378:metabolism; D002681:China; D019175:DNA Methylation; D004781:Environmental Exposure; D004784:Environmental Monitoring / Q000379:methods*; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D019570:Inhalation Exposure; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D016273:Occupational Exposure / Q000032:analysis*; D052638:Particulate Matter / Q000633:toxicity; D012107:Research Design; D012306:Risk; D017422:Sequence Analysis, DNA; D012907:Smoking / Q000009:adverse effects; D011795:Surveys and Questionnaires; D020080:Tandem Repeat Sequences / Q000235:genetics*
chemical_list: D000393:Air Pollutants; D015415:Biomarkers; D052638:Particulate Matter
keywords: DNA methylation; lung cancer; tandem repeats