title: Apoptotic capacity and risk of squamous cell carcinoma of the head and neck.
abstract: Tobacco smoke and alcohol drinking are the major risk factors for squamous cell carcinoma of the head and neck (SCCHN). Smoking and drinking cause DNA damage leading to apoptosis, and insufficient apoptotic capacity may favour development of cancer because of the dysfunction of removing damaged cells. In the present study, we investigated the association between camptothecin (CPT)-induced apoptotic capacity and risk of SCCHN in a North American population.
  
  
  
  In a case-control study of 708 SCCHN patients and 685 matched cancer-free controls, we measured apoptotic capacity in cultured peripheral blood lymphocytes in response to in vitro exposure to CPT by using the flow cytometry-based method.
  
  
  
  We found that the mean level of apoptotic capacity in the cases (45.9 ± 23.3%) was significantly lower than that in the controls (49.0 ± 23.1%) (P = 0.002). When we used the median level of apoptotic capacity in the controls as the cutoff value for calculating adjusted odds ratios, subjects with a reduced apoptotic capacity had an increased risk (adjusted odds ratio = 1.42, 95% confidence interval = 1.13-1.78, P = 0.002), especially for those who were age ≥57 (1.73, 1.25-2.38, 0.0009), men (1.76, 1.36-2.27, <0.0001) and ever drinkers (1.67, 1.27-2.21, 0.0003), and these variables significantly interacted with apoptotic capacity (Pinteraction= 0.015, 0.005 and 0.009, respectively). A further fitted prediction model suggested that the inclusion of apoptotic capacity significantly improved in the prediction of SCCHN risk.
  
  
  
  Individuals with a reduced CPT-induced apoptotic capacity may be at an increased risk of developing SCCHN, and apoptotic capacity may be a biomarker for susceptibility to SCCHN.
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: Peng
authors.initials: P
authors.lastname: Han
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: Department 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: Department 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: Guojun
authors.initials: G
authors.lastname: Li
authors.affiliation: Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Kouros
authors.initials: K
authors.lastname: Owzar
authors.affiliation: Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Jose P
authors.initials: JP
authors.lastname: Zevallos
authors.affiliation: Department 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: D000328:Adult; D000368:Aged; D000428:Alcohol Drinking / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002166:Camptothecin / Q000494:pharmacology; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000503:physiopathology*; D016022:Case-Control Studies; D005260:Female; D005434:Flow Cytometry; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000503:physiopathology*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects; D000077195:Squamous Cell Carcinoma of Head and Neck; D059004:Topoisomerase I Inhibitors / Q000494:pharmacology
chemical_list: D059004:Topoisomerase I Inhibitors; D002166:Camptothecin
keywords: Apoptosis; Apoptotic capacity; Biomarker; CPT; Head and neck cancer