Nicotine dependence phenotype, time to first cigarette, and risk of head and neck cancer

BACKGROUND: A behavioral phenotype that characterizes nicotine dependence, the time to first cigarette after waking, is hypothesized to increase the risk of head and neck cancer. METHODS: A case-control study of histologically confirmed head and neck cancer was conducted that included 1055 cases and 795 controls with a history of cigarette smoking. RESULTS: The pack-years-adjusted odds ratio was 1.42 (95% confidence interval (95% CI), 1.02-1.99) for an interval of 31 minutes to 60 minutes to first cigarette after waking and 1.59 (95% CI, 1.19-2.11) for an interval of 1 minute to 30 minutes. The risk estimates were similar when smoking was modeled as total years, smoking status (current vs for- mer), number of cigarettes smoked per day, years since quitting, and excess odds ratio. Findings were consistent for cancers of the floor of the mouth, palate, and pharynx. CONCLUSIONS: Time to first cigarette is an indicator of increased nicotine dependence, smoke uptake, and risk of head and neck cancer. This high-risk group of individuals would benefit from targeted smoking interventions. Cancer 2011;117:5377-82. V C 2011 American Cancer Society. The risk of head and neck cancer increases with the frequency and duration of cigarette smoking. 1-4 The physiological dependence on nicotine determines the degree of nicotine uptake and associated tobacco toxins. This is not readily quanti- fiable in population-based studies. Smoke uptake has traditionally been characterized by age of smoking onset, frequency, duration, and years since quitting. These measures have satisfactorily documented the high rates and risks of many cancers as well as cardiovascular disease from cigarette smoking despite the moderate association noted between self-reported measures of cigarette frequency and biochemical exposure markers. 5,6 The time to first cigarette (TTFC), an item of the Fagerstrom Test for Nicotine Dependence (FTND), 7 is a objective measure of nicotine dependence 8,9 and is associated with the many behavioral traits of nicotine addiction, including smok- ing amount, 10 inability to quit, 11,12 smoking relapse, 13 and tolerance. 14 Nicotine dependence can also be measured bio- chemically by quantifying the blood levels of cotinine, the major nicotine metabolite. The levels of cotinine are associated with the number of cigarettes smoked per day and, to a lesser extent, the nicotine content of cigarettes. A shorter time elapsed between waking and the first cigarette smoked recently was found to be associated with significantly higher levels of cotinine in several hundred current smokers who smoked � 5 cigarettes per day. 15 Two nicotine dependence pheno- types were found. The ''low'' dependent phenotype was characterized by smoking > 30 minutes after waking and smoking � 20 cigarettes per day. In this group, cotinine levels were relatively low but increased linearly with cigarette consumption. The ''high'' dependent phenotype was characterized by smoking � 30 minutes after waking but having a wide range in the number of cigarettes smoked (eg, 6-70 cigarettes smoked per day). In this group, cotinine levels were much higher but there were few differences noted in these levels by cigarette frequency. If the TTFC is an independent marker of nicotine dependence and tobacco smoke exposure, subjects with early TTFC might have an increased risk of smoking-related can- cers. The current study examined whether the TTFC is a predictor of oral and pharyngeal cancer risk.