Urinary Cotinine Is as Good a Biomarker as Serum Cotinine for Cigarette Smoking Exposure and Lung Cancer Risk Prediction

Background: Cotinine is a metabolite of nicotine. Serum and urinary cotinine are validated biomarkers for cigarette exposure. Their performance for lung cancer risk prediction has not been simultaneously examined in epidemiologic studies. Methods: A nested case-control study, including 452 incident lung cancer cases and 452 smoking-matched controls in the Shanghai cohort study, was conducted. Mass spectrometry-based methods were used to quantify cotinine in serum and urine samples collected from current smokers at baseline, on average 10 years before cancer diagnosis of cases. Logistic regression was used to estimate ORs, 95% confidence intervals (CI), and AUC ROC for lung cancer associated with higher levels of cotinine. Results: Serum and urinary cotinine levels were significantly higher in lung cancer cases than controls. Compared with the lowest quartile serum cotinine (<= 0.40 nmol/mL), the OR of lung cancer for smokers in the highest quartiles (>1.39 nmol/mL) was 5.46 (95% CI, 3.38-8.81). Similarly, the OR was 5.49 (95% CI, 3.39-8.87) for highest (>16.38 nmol/mg creatinine) relative to the lowest quartile of urinary total cotinine (<= 4.11 nmol/mg creatinine). A risk prediction model yielded an AUC of 0.72 (95% CI, 0.69-0.75) for serum cotinine and 0.72 (95% CI, 0.69-0.75) for urinary total cotinine combined with smoking history. Conclusions: Urinary and serum cotinine have the same performance in prediction of lung cancer risk for current smokers. Impact: Urinary cotinine is a noninvasive biomarker that can replace serum cotinine in risk prediction of future lung cancer risk for current smokers.