Larose TL, et al. - Whether circulating cotinine—a nicotine metabolite and biomarker of recent tobacco exposure—provides additional information on lung cancer risk beyond self-reported smoking, which is the principal measure used to assess lung cancer risk in epidemiological studies, was investigated. Researchers found a consistent association of circulating cotinine concentrations with lung cancer risk for current smokers. Moreover, relative to self-report smoking alone, these offer additional risk-discriminative information.

Methods

• In this study conducted in the Lung Cancer Cohort Consortium (LC3) involving 20 prospective cohort studies, measurements of pre-diagnostic serum cotinine concentrations were carried out in one laboratory on 5364 lung cancer cases and 5364 individually matched controls.
• Researchers, using conditional logistic regression, assessed the link between circulating cotinine and lung cancer.
• They also used receiver-operating characteristic (ROC) curve analysis and assessed if cotinine provided additional risk-discriminative information compared with self-reported smoking (smoking status, smoking intensity, smoking duration).

Results

• For current smokers, a strong positive association between cotinine and lung cancer risk was observed [odds ratio (OR ) per 500 nmol/L increase in cotinine (OR500): 1.39, 95% confidence interval (CI): 1.32–1.47].
• In former smokers, cotinine concentrations consistent with active smoking (≥115 nmol/L) (cases: 14.6%; controls: 9.2%) were commonly found while, such a finding was rarely reported in never smokers (cases: 2.7%; controls: 0.8%).
• Increased lung cancer risk was also exhibited by former and never smokers with cotinine concentrations indicative of active smoking (≥115 nmol/L).
• Compared with self-reported smoking alone (AUC_smoke: 0.66, 95% CI: 0.64–0.68), the risk-discriminative performance of cotinine combined with self-reported smoking (AUC_integrated: 0.69, 95% CI: 0.68–0.71) yielded a small improvement for current smokers (P=1.5x10^-9).