Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, Ontario, Canada.
Department of Family Medicine, Sinai Health System; Toronto, Ontario, Canada.
PLoS One. 2020 Aug 28;15(8):e0237723. doi: 10.1371/journal.pone.0237723. eCollection 2020.
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.
本研究旨在调查尼古丁依赖作为上呼吸道（UADT）癌症（包括肺癌和头颈部癌症[HNC]）的独立危险因素。该研究旨在分离尼古丁依赖的直接影响，独立于吸烟。
在加拿大安大略省进行了一项总计 4957 名参与者的病例对照研究，其中 2964 名被归类为当前或曾经吸烟者用于分析。使用尼古丁依赖 Fagerström 测试（FTND）测量所有吸烟者（2360 例 UADT 病例和 604 例对照）的尼古丁依赖情况。通过中介分析和调整后的逻辑回归模型，我们分解了尼古丁依赖的直接作用和吸烟持续时间的中介作用，以量化肺癌和 HNC 的风险。评估了人乳头瘤病毒（HPV）和癌症亚型的作用。
大多数个体尼古丁依赖行为与肺癌呈正相关，风险增加约 1.8 至 3.5 倍，与 HNC 的风险增加较小，为 1.4 至 2.3 倍。尼古丁依赖部分解释了肺癌（OR=1.20，95%CI=1.13-1.28）和 HNC（1.12，95%CI=1.04-1.19）风险的增加。与 HPV 阳性口咽癌（OR=1.05，95%CI=0.67-1.65）相比，尼古丁依赖对 HPV 阴性口咽癌（OR=3.06，95%CI=1.65-5.66）的风险影响更大。在考虑累积烟草暴露后，尼古丁依赖的直接作用仍然显著。
在考虑吸烟的情况下，尼古丁依赖增加了肺癌和 HNC 癌症的风险，表明尼古丁可能具有潜在的毒性作用。这些结果为考虑尼古丁暴露的安全性提供了信息。
