Nicotine dependence as a risk factor for upper aerodigestive tract (UADT) cancers: A mediation analysis

• Published in: PloS one Vol. 15; no. 8; p. e0237723
• Main Authors: Thomas, Sera, Carroll, June C, Brown, M Catherine, Chen, Zhou, Mirshams, Maryam, Patel, Devalben, Boyd, Kevin, Pierre, Andrew, Goldstein, David P, Giuliani, Meredith E, Xu, Wei, Eng, Lawson, Khodayari Moez, Elham, Liu, Geoffrey, Hung, Rayjean J
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 28.08.2020; Public Library of Science (PLoS)
• Subjects: Aged; Alcohol use; Biology and Life Sciences; Case-Control Studies; Cell adhesion & migration; Dependence; Digestive system cancer; Drug dependence; Exposure; Family medical history; Female; Head & neck cancer; Head and neck; Head and Neck Neoplasms - epidemiology; Head and Neck Neoplasms - etiology; Health aspects; Health care networks; Health risks; Human papillomavirus; Humans; Lung cancer; Lung diseases; Lung Neoplasms - epidemiology; Lung Neoplasms - etiology; Male; Mediation; Medicine and Health Sciences; Middle Aged; Nicotine; Nicotine - adverse effects; Ontario - epidemiology; Oropharyngeal cancer; Physical Sciences; Public health; Regression analysis; Regression models; Respiratory tract cancer; Risk analysis; Risk Assessment; Risk Factors; Smoking; Social Sciences; Statistical analysis; Time Factors; Tobacco; Tobacco smoking; Tobacco Use Disorder - complications; Tobacco Use Disorder - epidemiology; Toxicity; Ontario; Canada; Toronto Ontario Canada
• DOI: 10.1371/journal.pone.0237723
• ISSN: 1932-6203

This study investigated nicotine dependence as an independent risk factor for upper aerodigestive tract (UADT) cancers, including lung and head and neck cancers (HNC). The study aimed to isolate the direct effect of nicotine dependence, independent of tobacco smoking. A case-control study with a total of 4957 participants was conducted in Ontario, Canada, of which 2964 categorized as either current or former smokers were used in the analysis. Nicotine dependence of ever-smokers (2360 UADT cases and 604 controls) was measured using the Fagerström Test for Nicotine Dependence. Using mediation analyses and adjusted logistic regression models, we decomposed the direct effect of nicotine dependence and the mediated effect of smoking duration to quantify the risks of lung and HNC. The role of human papillomavirus (HPV) and cancer subtypes were assessed. Most individual nicotine dependence behaviours showed positive associations with lung cancer with approximately 1.8 to 3.5-fold risk increase, and to lesser extent with 1.4 to 2.3-fold risk for HNC. Nicotine dependence is partially accountable for increased risks of lung cancer (OR = 1.20, 95%CI = 1.13-1.28) and HNC (1.12, 95%CI = 1.04-1.19). Nicotine dependence had a greater effect on the risk of HPV-negative oropharyngeal cancer (OR = 3.06, 95%CI = 1.65-5.66) in comparison to HPV-positive oropharyngeal cancer (OR = 1.05, 95%CI = 0.67-1.65). The direct effects of nicotine dependence remained significant after accounting for cumulative tobacco exposures. Nicotine dependence increases the risks of lung and HNC cancers after accounting for tobacco smoking, suggesting potential toxic effects of nicotine. These results are informative for the safety consideration of nicotine exposures.