title: Reduced DNA double-strand break repair capacity and risk of squamous cell carcinoma of the head and neck--A case-control study.
abstract: Tobacco smoke and alcohol use play important roles in the etiology of squamous cell carcinoma of the head and neck (SCCHN). Smoking causes DNA damage, including double-strand DNA breaks (DSBs), that leads to carcinogenesis. To test the hypothesis that suboptimal DSB repair capacity is associated with risk of SCCHN, we applied a flow cytometry-based method to detect the DSB repair phenotype first in four EBV-immortalized human lymphoblastoid cell lines and then in human peripheral blood T-lymphocytes (PBTLs). With this blood-based laboratory assay, we conducted a pilot case-control study of 100 patients with newly diagnosed, previously untreated SCCHN and 124 cancer-free controls of non-Hispanic whites. We found that the mean DSB repair capacity level was significantly lower in cases (42.1%) than that in controls (54.4%) (P<0.001). When we used the median DSB repair capacity level in the controls as the cutoff value for calculating the odds ratios (ORs) with adjustment for age, sex, smoking and drinking status, the cases were more likely than the controls to have a reduced DSB repair capacity (adjusted OR=1.93; 95% confidence interval, CI=1.04-3.56, P=0.037), especially for those subjects who were ever drinkers (adjusted OR=2.73; 95% CI=1.17-6.35, P=0.020) and had oropharyngeal tumors (adjusted OR=2.17; 95% CI=1.06-4.45, P=0.035). In conclusion, these findings suggest that individuals with a reduced DSB repair capacity may be at an increased risk of developing SCCHN. Larger studies are warranted to confirm these preliminary findings.
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Zhensheng
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Fengqin
authors.initials: F
authors.lastname: Gao
authors.affiliation: Departments of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Kristina R
authors.initials: KR
authors.lastname: Dahlstrom
authors.affiliation: Departments of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA; Department of Epidemiology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA.
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. Electronic address: qingyi.wei@duke.edu.
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
mesh_terms: D000428:Alcohol Drinking / Q000453:epidemiology; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded; D005260:Female; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D059767:Recombinational DNA Repair; D012907:Smoking / Q000453:epidemiology
keywords: Biomarker; DNA damage; DNA double-strand breaks repair capacity; Head and neck cancer; γ-H2AX