Tobacco-related urinary biomarkers and lung cancer risk in women, a case-cohort analysis

The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents-polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, nicotine, and volatile organic compounds-and lung cancer incidence among US women.

In a case-cohort study nested within the Sister Study (women aged 35-74 years at baseline, enrolled 2003-2009), data were obtained for a random subcohort and all remaining incident lung cancers through September 2017 (median follow-up = 9.6 years), stratified by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, others) and smoking status (current, former, never). The analytic sample included 356 cases and 433 noncases. We quantified 30 biomarkers in baseline urine samples and calculated hazard ratios (HRs) for associations between 1-unit increase in biomarker concentrations (log-scale) and lung cancer incidence using weighted Cox regression models adjusted for urinary creatinine and demographic, health, and lifestyle factors.

Among women who were currently smoking at enrollment, positive associations were observed for biomarkers of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, pyrene, fluorene; HRs = 1.4-5.3), tobacco-specific nitrosamines (particularly 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [nicotine-derived nitrosamine ketone]; HRs = 1.3-2.2), and volatile organic compounds (xylene, acrylamide, acrylonitrile, 1,2-dibromoethane and/or vinyl-chloride and/or ethylene-oxide and/or acrylonitrile, acrolein, styrene and/or ethylbenzene, benzene, dimethylformamide and/or methylisocyanate, 1,3-butadiene, crotonaldehyde, isoprene; HRs = 1.6-4.4). Associations with biomarkers of most polycyclic aromatic hydrocarbons, nicotine-derived nitrosamine ketone, xylene, and dimethylformamide and/or methylisocyanate remained after additional adjustment for smoking frequency, duration, and nicotine metabolites. In women who did not smoke, positive associations were observed for styrene and/or ethylbenzene and dimethylformamide and/or methylisocyanate biomarkers.

Exposure to polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, and several volatile organic compounds through tobacco smoking were associated with increased lung cancer risk among women.