Abstract 863: Urinary levels of a polycyclic aromatic hydrocarbon metabolite in relation to lung cancer development in cigarette smokers of the Shanghai Cohort Study

Abstract

Abstract Background: Polycyclic aromatic hydrocarbons (PAH) are believed to be among the principal causative agents for lung cancer in smokers, but epidemiologic data directly linking PAH biomarkers to lung cancer in humans are lacking. A validate bimarker of PAH exposure plus metabolism, r-1,t-2,3,c-4-tetrahydroxy1,2,3,4-tetrahydrophenanthrene (PheT), is a metabolite of phenanthrene, the simplest PAH with a bay region, a feature closely associated with carcinogenicity. Methods: The association between PheT in pre-diagnostic urines and risk of lung cancer amoung current smokers was examined in the Shanghai Cohort Study, which enrolled 18,244 men aged 45-64 years in Shanghai, China during 1/1/86 − 9/30/89. In addition to in-person interviews for cigarette smoking and other lifestyle factors, we collected blood and urine samples from all cohort participants. The cohort has been actively followed for cancer incidence. A case-control study nested within the cohort was conducted involving 535 lung cancer patients (cases) who smoked cigarettes at recruitment and 535 current smokers (controls) who were individually matched to the index cases by age and date of urine collection. PheT in urines of all cases and controls was quantified by gas chromatography-mass spectrometry (GC-MS). In addition, we have so far completed the quantification of total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL; a metabolite of the tobacco-specific lung carcinogen NNK) and cotinine on a subset of the study subjects (137 case-control pairs). The relative risk (RR) and 95% confidence interval (CI) for lung cancer with urinary PheT alone and in combination with total NNAL were estimated using a conditional logistic regression method. Results: Urinary levels of PheT were significantly higher for cases than controls after adjustment for smoking intensity and duration [geometric mean 31.7 (95% CI 30.2-33.3) vs 28.1 (95% CI 26.8-29.6) pmol/mg creatinine, P = 0.001]. Relative to the lowest quintile, RRs (95% CIs) for the 2nd, 3rd, 4th, and 5th quintile of total PheT were 1.49 (0.94-2.34), 1.24 (0.78-1.96), 1.73 (1.09-2.75), and 2.64 (1.63-4.28), respectively (P for trend = 0.0001). Based on the subset, smokers in the highest tertiles of urinary PheT and total NNAL exhibited a 13.8-fold (95% CI 2.0-96.1) increased risk for lung cancer relative to smokers with comparable levels of urinary cotinine and smoking intensity and duration but being in the lowest tertiles of urinary PheT and total NNAL. Conclusion: Findings of this study directly link a specific biomarker for PAH uptake and metabolism to lung cancer development in humans. Urinary PheT is an independent predictor of lung cancer risk in smokers. In addition to urinary total NNAL, an established biomarker of NNK uptake, urinary PheT can be another member of an individual-based predictive model for lung cancer risk in a smoker. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 863.