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Risk assessment of esophageal adenocarcinoma using ?-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 ?-H2AX is an early cellular response to DNA double-strand breaks (DSB). We hypothesize that higher level of radiation-induced ?-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 ?-H2AX levels in PBLs from 211 patients with esophageal adenocarcinoma and 211 healthy controls. The ratio of induced ?-H2AX level to baseline level was used to evaluate individual susceptibility to DSBs. Relative risks for esophageal adenocarcinoma associated with ?-H2AX were assessed by multivariable logistic regression analysis. RESULTS:Radiation-induced ?-H2AX level and the ?-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 ?-H2AX ratio [OR = 2.94; 95% confidence interval (CI), 1.83-4.72]. Quartile analyses showed significant dose-response associations between higher ?-H2AX ratio and increased risk of esophageal adenocarcinoma (Ptrend, 1.64E-06). In addition, joint effect between ?-H2AX ratio and smoking was observed: smokers who had high ?-H2AX ratio exhibited the highest risk of esophageal adenocarcinoma (OR = 5.53; 95% CI, 2.71-11.25) compared with never smokers with low ?-H2AX ratio. CONCLUSION:Radiation-induced DNA damage assessed by ?-H2AX ratio is associated with an increased risk of esophageal adenocarcinoma. IMPACT:?-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.

SUBMITTER: Xu E

PROVIDER: S-EPMC3824382 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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Risk assessment of esophageal adenocarcinoma using γ-H2AX assay.

Xu Enping E Gong Yilei Y Gu Jian J Jie Lin L Ajani Jaffer A JA Wu Xifeng X

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20130731 10

<h4>Background</h4>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.<h4>Methods</h4>Laser scanning cytometer-based immunocytochemical method was used to measure baseline and irradiation-induc ...[more]

PMID: 23904462

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Project description:PurposeEsophageal adenocarcinoma (EAC) is the most common type of esophageal cancer in Western countries. It is usually detected at an advanced stage and has a poor prognosis. The aim of this study was to identify key genes and miRNAs in EAC.MethodsThe mRNA microarray data sets GSE1420, GSE26886, and GSE92396 and miRNA data set GSE16456 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were obtained using R software. Functional enrichment analysis was performed using the DAVID database. A protein-protein interaction (PPI) network and functional modules were established using the STRING database and visualized by Cytoscape. The targets of the DEMs were predicted using the miRecords database, and overlapping genes between DEGs and targets were identified. The prognosis-related overlapping genes were identified using Kaplan-Meier analysis and Cox proportional hazard analysis based on The Cancer Genome Atlas (TCGA) database. The differential expression of these prognosis-related genes was validated using the expression matrix in the TCGA database.ResultsSeven hundred and fifteen DEGs were obtained, consisting of 313 upregulated and 402 downregulated genes. The PPI network consisted of 281 nodes; 683 edges were constructed and 3 functional modules were established. Forty-four overlapping genes and 56 miRNA- mRNA pairs were identified. Five genes, FAM46A, RAB15, SLC20A1, IL1A, and ACSL1, were associated with overall survival or relapse-free survival. FAM46A and IL1A were found to be independent prognostic indicators for overall survival, and FAM46A, RAB15, and SLC20A1 were considered independent prognostic indicators for relapse-free survival. Among them, the overexpression of RAB15 and SLC20A1 and lower expression of ACSL1 were also identified in EAC tissues based on the expression matrix in the TCGA database.ConclusionThese prognosis-related genes and differentially expressed miRNA have provided potential biomarkers for EAC diagnosis and treatment.

Dataset Information

Risk assessment of esophageal adenocarcinoma using ?-H2AX assay.

Publications

Risk assessment of esophageal adenocarcinoma using γ-H2AX assay.

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