title: Global DNA methylation patterns in Barrett's esophagus, dysplastic Barrett's, and esophageal adenocarcinoma are associated with BMI, gender, and tobacco use.
abstract: The risk of developing Barrett's esophagus (BE) and/or esophageal adenocarcinoma (EAC) is associated with specific demographic and behavioral factors, including gender, obesity/elevated body mass index (BMI), and tobacco use. Alterations in DNA methylation, an epigenetic modification that can affect gene expression and that can be influenced by environmental factors, is frequently present in both BE and EAC and is believed to play a role in the formation of BE and its progression to EAC. It is currently unknown whether obesity or tobacco smoking influences the risk of developing BE/EAC via the induction of alterations in DNA methylation. To investigate this possibility, we assessed the genome-wide methylation status of 81 esophageal tissues, including BE, dysplastic BE, and EAC epithelia using HumanMethylation450 BeadChips (Illumina).
  
  
  
  We found numerous differentially methylated loci in the esophagus tissues when comparing males to females, obese to lean individuals, and smokers to nonsmokers. Differences in DNA methylation between these groups were seen in a variety of functional genomic regions and both within and outside of CpG islands. Several cancer-related pathways were found to have differentially methylated genes between these comparison groups.
  
  
  
  Our findings suggest obesity and tobacco smoking may influence DNA methylation in the esophagus and raise the possibility that these risk factors affect the development of BE, dysplastic BE, and EAC through influencing the epigenetic status of specific loci that have a biologically plausible role in cancer formation.
authors: Gastroenterology Section, VA Puget Sound Health Care System, Seattle, WA 98108 USA ; Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA ; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors: Andrew M
authors: AM
authors: Kaz
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA.
authors: Chao-Jen
authors: CJ
authors: Wong
authors: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA.
authors: Vinay
authors: V
authors: Varadan
authors: Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 USA.
authors: Joseph E
authors: JE
authors: Willis
authors: Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, OH 44106 USA ; Division of Gastroenterology, Case Western Reserve University School of Medicine, Cleveland, OH 44106 USA.
authors: Amitabh
authors: A
authors: Chak
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109 USA ; Department of Medicine, University of Washington School of Medicine, Seattle, WA 98195 USA.
authors: William M
authors: WM
authors: Grady
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D001471:Barrett Esophagus / Q000235:genetics*; D015992:Body Mass Index; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D004938:Esophageal Neoplasms / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D009765:Obesity / Q000150:complications* / Q000453:epidemiology; D012307:Risk Factors; D012737:Sex Factors; D064424:Tobacco Use / Q000009:adverse effects*
keywords: Barrett’s esophagus; DNA methylation; Esophageal adenocarcinoma; Obesity; Tobacco use; Waist-to-hip ratio