title: Risk assessment of esophageal adenocarcinoma using γ-H2AX assay.
abstract: BACKGROUND
  Mutagen-induced DNA damage as measured in peripheral blood lymphocytes (PBL) has been associated with increased risks of cancers. The formation of γ-H2AX is an early cellular response to DNA double-strand breaks (DSB). We hypothesize that higher level of radiation-induced γ-H2AX in PBLs may be associated with an increased risk of esophageal adenocarcinoma.
  
  
  METHODS
  Laser scanning cytometer-based immunocytochemical method was used to measure baseline and irradiation-induced γ-H2AX levels in PBLs from 211 patients with esophageal adenocarcinoma and 211 healthy controls. The ratio of induced γ-H2AX level to baseline level was used to evaluate individual susceptibility to DSBs. Relative risks for esophageal adenocarcinoma associated with γ-H2AX were assessed by multivariable logistic regression analysis.
  
  
  RESULTS
  Radiation-induced γ-H2AX level and the γ-H2AX ratio were significantly higher in cases than in controls. Dichotomized at the median in controls, a significantly increased risk for esophageal adenocarcinoma was observed in association with high γ-H2AX ratio [OR = 2.94; 95% confidence interval (CI), 1.83-4.72]. Quartile analyses showed significant dose-response associations between higher γ-H2AX ratio and increased risk of esophageal adenocarcinoma (Ptrend, 1.64E-06). In addition, joint effect between γ-H2AX ratio and smoking was observed: smokers who had high γ-H2AX ratio exhibited the highest risk of esophageal adenocarcinoma (OR = 5.53; 95% CI, 2.71-11.25) compared with never smokers with low γ-H2AX ratio.
  
  
  CONCLUSIONS
  Radiation-induced DNA damage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma.
  
  
  CONCLUSIONS
  γ-H2AX assay is a new and robust method to measure DSB damage in PBLs, which can be used to assess mutagen sensitivity and esophageal adenocarcinoma risk.
authors.affiliation: Authors' Affiliations: Departments of Epidemiology and Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas; and Department of Pathology, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China.
authors.forename: Enping
authors.initials: E
authors.lastname: Xu
authors.forename: Yilei
authors.initials: Y
authors.lastname: Gong
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Lin
authors.initials: L
authors.lastname: Jie
authors.forename: Jaffer A
authors.initials: JA
authors.lastname: Ajani
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D053903:DNA Breaks, Double-Stranded; D004938:Esophageal Neoplasms / Q000097:blood* / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D006657:Histones / Q000097:blood*; D006801:Humans; D047569:Laser Scanning Cytometry; D008214:Lymphocytes / Q000737:chemistry; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment
chemical_list: C468783:H2AX protein, human; D006657:Histones
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