title: Gene-expression profiling of buccal epithelium among non-smoking women exposed to household air pollution from smoky coal.
abstract: In China's rural counties of Xuanwei and Fuyuan, lung cancer rates are among the highest in the world. While the elevated disease risk in this population has been linked to the usage of smoky (bituminous) coal as compared to smokeless (anthracite) coal, the underlying molecular changes associated with this exposure remains unclear. To understand the physiologic effects of smoky coal exposure, we analyzed the genome-wide gene-expression profiles in buccal epithelial cells collected from healthy, non-smoking female residents of Xuanwei and Fuyuan who burn smoky (n = 26) and smokeless (n = 9) coal. Gene-expression was profiled via microarrays, and changes associated with coal type were correlated to household levels of fine particulate matter (PM2.5) and polycyclic aromatic hydrocarbons (PAHs). Expression levels of 282 genes were altered with smoky versus smokeless coal exposure (P < 0.005), including the 2-fold increase of proinflammatory IL8 and decrease of proapoptotic CASP3. This signature was more correlated with carcinogenic PAHs (e.g. Benzo[a]pyrene; r = 0.41) than with non-carcinogenic PAHs (e.g. Fluorene; r = 0.08) or PM2.5 (r = 0.05). Genes altered with smoky coal exposure were concordantly enriched with tobacco exposure in previously profiled buccal biopsies of smokers and non-smokers (GSEA, q < 0.05). This is the first study to identify a signature of buccal epithelial gene-expression that is associated with smoky coal exposure, which in part is similar to the molecular response to tobacco smoke, thereby lending biologic plausibility to prior epidemiological studies that have linked this exposure to lung cancer risk.
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA, Bioinformatics Program, Boston University, Boston, MA 02215, USA.
authors.forename: Teresa W
authors.initials: TW
authors.lastname: Wang
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Roel C H
authors.initials: RC
authors.lastname: Vermeulen
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: Wei
authors.initials: W
authors.lastname: Hu
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Xiao
authors.affiliation: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Yuriy
authors.initials: Y
authors.lastname: Alekseyev
authors.affiliation: School of Public Health, The University of Hong Kong, Hong Kong, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Xu
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands, School of Public Health, University of Washington, Seattle, WA 98195, USA.
authors.forename: Boris
authors.initials: B
authors.lastname: Reiss
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA, Bioinformatics Program, Boston University, Boston, MA 02215, USA.
authors.forename: Katrina
authors.initials: K
authors.lastname: Steiling
authors.affiliation: Division of Environmental Epidemiology, Institute for Risk Assessment Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: George S
authors.initials: GS
authors.lastname: Downward
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: Debra T
authors.initials: DT
authors.lastname: Silverman
authors.affiliation: China National Environmental Monitoring Center, Beijing, China and.
authors.forename: Fusheng
authors.initials: F
authors.lastname: Wei
authors.affiliation: China National Environmental Monitoring Center, Beijing, China and.
authors.forename: Guoping
authors.initials: G
authors.lastname: Wu
authors.affiliation: Qujing Center for Diseases Control and Prevention, Qujing, China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Li
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA, Bioinformatics Program, Boston University, Boston, MA 02215, USA, Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
authors.forename: Marc E
authors.initials: ME
authors.lastname: Lenburg
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.affiliation: Division of Computational Biomedicine, Boston University School of Medicine, Boston, MA 02118, USA, Bioinformatics Program, Boston University, Boston, MA 02215, USA, Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, MA 02118, USA, aspira@bu.edu.
authors.forename: Avrum
authors.initials: A
authors.lastname: Spira
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD 20850, USA.
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000328:Adult; D000368:Aged; D016902:Air Pollution, Indoor; D003031:Coal; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D019570:Inhalation Exposure; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism*; D005810:Multigene Family; D012906:Smoke; D059467:Transcriptome
chemical_list: D003031:Coal; D012906:Smoke