Enping Xu1, Yilei Gong, Jian Gu, Lin Jie, Jaffer A Ajani, Xifeng Wu. 1. 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.
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. CONCLUSION: Radiation-induced DNA damage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. IMPACT: 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.
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. CONCLUSION: Radiation-induced DNA damage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. IMPACT: 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: Xifeng Wu; Margaret R Spitz; Christopher I Amos; Jie Lin; Lina Shao; Jian Gu; Mariza de Andrade; Neal L Benowitz; Peter G Shields; Gary E Swan Journal: Cancer Res Date: 2006-06-15 Impact factor: 12.701
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