TY - JOUR
T1 - Risk assessment of esophageal adenocarcinoma using γ-H2AX assay
AU - Xu, Enping
AU - Gong, Yilei
AU - Gu, Jian
AU - Jie, Lin
AU - Ajani, Jaffer A.
AU - Wu, Xifeng
PY - 2013/10
Y1 - 2013/10
N2 - Background: Mutagen-inducedDNAdamage 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-inducedDNAdamage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. Impact: g-H2AX assay is a newand robustmethod tomeasure DSB damage in PBLs, which can be used to assess mutagen sensitivity and esophageal adenocarcinoma risk.
AB - Background: Mutagen-inducedDNAdamage 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-inducedDNAdamage assessed by γ-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. Impact: g-H2AX assay is a newand robustmethod tomeasure DSB damage in PBLs, which can be used to assess mutagen sensitivity and esophageal adenocarcinoma risk.
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U2 - 10.1158/1055-9965.EPI-13-0485
DO - 10.1158/1055-9965.EPI-13-0485
M3 - Article
C2 - 23904462
AN - SCOPUS:84886426448
SN - 1055-9965
VL - 22
SP - 1797
EP - 1804
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 10
ER -