There is wide variability in cotinine levels per cigarette smoked. We hypothesized that in addition to smoking frequency, other behavioral measures of nicotine dependence, such as the time to first cigarette after waking, are associated with cotinine levels. To test this hypothesis, we measured plasma and urinary cotinine in a community-based study of 252 black and white daily cigarette smokers. Among one pack per day smokers, plasma cotinine levels varied from 16 to 1,180 ng/mL, a 74-fold difference. Two nicotine dependence phenotypes were discerned by time after waking. Subjects in the “low” dependent phenotype smoked >30 minutes after waking and nearly all smoked ≤20 cigarettes per day. Cotinine levels increased linearly with cigarette consumption in this group. Subjects in the “high” dependent phenotype smoked ≤30 minutes after waking but had a wide range in the frequency of daily cigarettes (6-70). Compared with the low dependent phenotype, there were relatively small differences in cotinine by cigarette frequency with evidence of a plateau effect in heavy smokers (∼30). After adjusting for cigarette frequency, the levels of cotinine by time to first cigarette were as follows: ≤5 minutes, 437 [95% confidence limits (CL), 380-494]; 6 to 30 minutes, 352 (95% CL, 291-413), 31 to 60 minutes, 229 (95% CL, 140-317), and >60 minutes, 215 (95% CL, 110-321). Similar findings were observed for urinary cotinine. These findings suggest that the time to first cigarette is a strong predictor of nicotine uptake and should be considered in the design of smoking interventions. (Cancer Epidemiol Biomarkers Prev 2009;18(12):3415–20)

Menthol is a controversial cigarette additive because its physiologic or pharmacologic effects may possibly increase the risk for cancer and its targeted market is the Black community. In a community-based cross-sectional study on 525 Black and White volunteers, we compared levels of urinary and plasma cotinine, plasma thiocyanate, urinary 4-(N-nitrosomethylamino)-1-(3-pyridyl)-1-butanol (NNAL), and its detoxified form (NNAL-Gluc) between menthol and nonmenthol smokers. In regression models that adjusted for daily cigarette intake, no significant differences were observed in the concentration of these biomarkers by menthol status in both races. There was no significant association between high Fagerstrom nicotine dependence scores and the use of menthol cigarettes (odds ratio, 1.1; 95% confidence interval, 0.6-2.0), but an increased risk was observed with smoking a cigarette soon (≤30 minutes) after waking (odds ratio, 2.1; 95% confidence interval, 1.0-3.8). The ratio of NNAL-Gluc to NNAL, a possible indicator of lung cancer risk, was significantly lower in menthol versus nonmenthol smokers. The NNAL-Gluc/NNAL ratio was 34% lower in Whites (P < 0.01) and 22% lower in Blacks. In subsequent human liver microsome studies, menthol inhibited the rate of NNAL-O-glucuronidation and NNAL-N-glucuronidation. Collectively, these results show that menthol does not affect biological exposure to tobacco smoke constituents but indicates that menthol might inhibit the detoxification of the potent lung carcinogen NNAL. (Cancer Epidemiol Biomarkers Prev 2009;18(1):35–41)

Talc, like asbestos, is a silicate that has been studied in relation to cancer risk. Several studies conducted over the past 25 years found an association between perineal talc powders and ovarian cancer. The summary relative risk is about 1.3 (95% confidence intervals 1.2–1.5) and these data have been interpreted as supporting a causal role. In this review article, we discuss the chemical and morphological features of talc and asbestos, and explain why despite their similar chemical classification talc does not possess asbestos-like carcinogenic properties. The heterogeneity in the perineal dusting studies has raised important concerns over the validity of the exposure measurements, and the lack of a consistent dose–response effect limits making causal inferences. Perhaps more importantly, whereas it is unknown whether external talc dust enters the female reproductive tract, measures of internal talc exposure such as talc-dusted diaphragms and latex condoms show no relationship with ovarian cancer risk. In addition, the therapeutic use of high dose cosmetic grade talc for pleurodesis has not been shown to cause cancer in patients receiving these treatment modalities. Talc is not genotoxic. Mechanistic, pathology and animal model studies have not found evidence for a carcinogenic effect. In summary, these data collectively do not indicate that cosmetic talc causes ovarian cancer.

Context: The validity of urinary correction standards has not been established for most analytes. Methods: We compared urinary creatinine and specific gravity as dilution correction standards for cotinine in a community-based study of smokers. Results: Models of blood cotinine regressed against CR or SG (measured by total soluble solids) significantly improved the fit compared to a model without a dilution measure (P < 0.01). There were no differences in model fit between CR- and SG-corrected values. Both CR and SG were significant predictors of urinary cotinine regressed against cigarettes smoked per day (P < 0.01). Conclusion: CR and SG are valid and interchangeable correction standards.

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 former), 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;. © 2011 American Cancer Society.

BACKGROUND: A behavioral phenotype that characterizes nicotine dependence, the time to first cigarette after waking, is hypothesized to increase the risk of lung cancer. METHODS: A case‐control study of histologically confirmed lung cancer was conducted. The current analysis included 4775 lung cancer cases and 2835 controls who were regular cigarette smokers. RESULTS: Compared with subjects who smoked their first cigarette > 60 minutes after waking, the pack‐years–adjusted odds ratio was 1.31 (95% confidence interval [95% CI], 1.11‐1.54) for subjects who smoked 31 minutes to 60 minutes after waking and 1.79 (95% CI, 1.56‐2.07) for subjects who smoked within 30 minutes of waking. The risk estimates were similar when smoking was modeled as total years, smoking status (current vs former), number of cigarettes smoked per day, years since quitting, and excess odds ratio. The findings were consistent for all histologic types of lung cancer. CONCLUSIONS: The findings of the current study indicate that a specific nicotine dependence phenotype that is associated with the amount of smoke uptake per cigarette is independently associated with lung cancer risk. These findings may help to identify high‐risk individuals who would benefit from targeted interventions. Cancer 2011;. © 2011 American Cancer Society.