title: Ionizing radiation-induced γ-H2AX activity in whole blood culture and the risk of lung cancer.
abstract: BACKGROUND
  Phenotypic biomarkers of DNA damage repair may enhance cancer risk prediction. The γ-H2AX formed at the sites of double-strand break (DSB) after ionizing radiation is a specific marker of DNA damage.
  
  
  METHODS
  In an ongoing case-control study, the baseline and ionizing radiation-induced γ-H2AX levels in peripheral blood lymphocytes (PBL) from frequency-matched 306 untreated patients with lung cancer and 306 controls were measured by a laser scanning cytometer-based immunocytochemical method. The ratio of ionizing radiation-induced γ-H2AX level to the baseline was used to evaluate interindividual variation of DSB damage response and to assess the risk of lung cancer by using unconditional multivariable logistic regression with adjustment of age, sex, ethnicity, smoking status, family history of lung cancer, dust exposure, and emphysema.
  
  
  RESULTS
  The mean γ-H2AX ratio was significantly higher in cases than controls (1.46 ± 0.14 vs. 1.41 ± 0.12, P < 0.001). Dichotomized at the median in controls, high γ-H2AX ratio was significantly associated with increased risk of lung cancer [OR = 2.43; 95% confidence interval (CI): 1.66-3.56]. There was also a significant dose-response relationship between γ-H2AX ratio and lung cancer risk in quartile analysis. Analysis of joint effects with other epidemiologic risk factors revealed elevated risk with increasing number of risk factors.
  
  
  CONCLUSIONS
  γ-H2AX activity as shown by measuring DSB damage in ionizing radiation-irradiated PBLs may be a novel phenotypic marker of lung cancer risk.
  
  
  CONCLUSIONS
  γ-H2AX assay is a robust and quantifiable image-based cytometer method that measures mutagen-induced DSB response in PBLs as a potential biomarker in lung cancer risk assessment.
authors.affiliation: Corresponding Author: Xifeng Wu, Department of Epidemiology, Unit 1340, The University of Texas MD Anderson Cancer Center, 1155 Herman Pressler, Houston, TX 77030, USA.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: He
authors.forename: Yilei
authors.initials: Y
authors.lastname: Gong
authors.forename: Jie
authors.initials: J
authors.lastname: Lin
authors.forename: David W
authors.initials: DW
authors.lastname: Chang
authors.forename: Jian
authors.initials: J
authors.lastname: Gu
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.forename: Xifeng
authors.initials: X
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D002294:Carcinoma, Squamous Cell / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D016022:Case-Control Studies; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects*; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006657:Histones / Q000378:metabolism* / Q000528:radiation effects; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000209:etiology*; D008214:Lymphocytes / Q000378:metabolism* / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011839:Radiation, Ionizing; D012307:Risk Factors; D055752:Small Cell Lung Carcinoma / Q000097:blood / Q000175:diagnosis / Q000209:etiology
chemical_list: D014408:Biomarkers, Tumor; C468783:H2AX protein, human; D006657:Histones