Smoking-promoted oxidative DNA damage response is highly correlated to lung carcinogenesis

// Chao Cao 1, * , Tianwen Lai 1, * , Miao Li 1 , Hongbin Zhou 1 , Dan Lv 1, 2 , Zaichun Deng 2 , Songmin Ying 1 , Zhihua Chen 1 , Wen Li 1 , Huahao Shen 1, 3 1 Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China 2 Department of Respiratory Medicine, Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, China 3 State Key Laboratory for Respiratory Diseases, Guangzhou, China * These authors have contributed equally to this work Correspondence to: Huahao Shen, e-mail: huahaoshen@163.com Wen Li, e-mail: liwenzjhz0408@163.com Keywords: lung cancer, smoking, oxidative DNA damage, 8-OHdG, biomarker Received: November 08, 2015     Accepted: January 31, 2016     Published: March 01, 2016 ABSTRACT Oxidative stress induced by tobacco smoking is one of the main causes of DNA damage and is known to be involved in various cancers. Smoking is the leading cause of lung cancer, while the role of cigarette smoke-induced oxidative DNA damage response during lung carcinogenesis is largely unknown. In this study, we investigated oxidative DNA damage response levels in smoking and nonsmoking patients with lung cancer, and evaluated the potential diagnostic value of 8-OHdG for lung cancer. We observed a higher level of 8-OHdG expression and secretion in airways of lung cancer patients than that of noncancer controls. 8-OHdG expression was associated with the TNM stages. Additionally, cigarette smoke-induced oxidative DNA damage response was observed in bronchial epithelial cells in vitro and in vivo . A statistical significance correlation was found between the levels of 8-OHdG and smoking index. With a cut-off value of 2.86 ng/ml, 8-OHdG showed a sensitivity and specificity of 70.0% and 73.7%, respectively, to identify a patient with lung cancer. These findings not only underscore the importance of smoking in oxidative DNA damage response of lung cancer patients, but also suggest 8-OHdG as a potential diagnostic biomarker for lung cancer.