Zhensheng Liu1, Hongliang Liu1, Peng Han1, Fengqin Gao1, Kristina R Dahlstrom2, Guojun Li3, Kouros Owzar4, Jose P Zevallos5, Erich M Sturgis3, Qingyi Wei6. 1. Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Medicine, Duke University School of Medicine, Durham, NC 27710, USA. 2. Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77030, USA. 3. 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. 4. Duke Cancer Institute, Duke University Medical Center, Durham, NC 27710, USA; Department of Biostatistics and Bioinformatics, Duke University Medical Center, Durham, NC 27710, USA. 5. 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. 6. 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.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSION: 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: Yuan-Chin Amy Lee; Paolo Boffetta; Erich M Sturgis; Qingyi Wei; Zuo-Feng Zhang; Joshua Muscat; Philip Lazarus; Elena Matos; Richard B Hayes; Deborah M Winn; David Zaridze; Victor Wünsch-Filho; Jose Eluf-Neto; Sergio Koifman; Dana Mates; Maria Paula Curado; Ana Menezes; Leticia Fernandez; Alexander W Daudt; Neonila Szeszenia-Dabrowska; Eleonora Fabianova; Peter Rudnai; Gilles Ferro; Julien Berthiller; Paul Brennan; Mia Hashibe Journal: Cancer Epidemiol Biomarkers Prev Date: 2008-08 Impact factor: 4.254