Journal
EUROPEAN JOURNAL OF CANCER
Volume 72, Issue -, Pages 166-176Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.ejca.2016.11.018
Keywords
Biomarker; Apoptosis; CPT; Apoptotic capacity; Head and neck cancer
Categories
Funding
- National Institutes of Health [R01 ES011740, R01 CA131274, P50 CA097007, CA 16672]
- Duke Cancer Institute
- Duke University Medical Center
- Duke Cancer Institute as part of the P30 Cancer Center Support Grant [NIH CA014236]
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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 (Finteraction = 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. (C) 2016 Elsevier Ltd. All rights reserved.
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