Urinary levels of cigarette smoke constituent metabolites are prospectively associated with lung cancer development in smokers

Jian Min Yuan, Yu Tang Gao, Sharon E Murphy, Steven G Carmella, Renwei Wang, Yan Zhong, Kristin A. Moy, Andrew B. Davis, Li Tao, Menglan Chen, Shaomei Han, Heather H Nelson, Mimi C. Yu, Stephen S Hecht

Research output: Contribution to journalArticlepeer-review

66 Scopus citations

Abstract

Polycyclic aromatic hydrocarbons (PAH) are believed to beamong the principal causative agents for lung cancer in smokers, but no epidemiologic studies have evaluated the relationship of PAH uptake and metabolism to lung cancer. In this study, we quantified prediagnostic urinary levels of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a validated biomarker of PAH uptake and metabolism, as well as 4-(methylnitrosamino)-1- (3-pyridyl)-1-butanol and its glucuronides (total NNAL), and cotinine and its glucuronides (total cotinine), validated biomarkers of uptake of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, and nicotine, respectively, in relation to lung cancer risk among current smokers in a nested case-control study within a cohort of 18,244 Chinese men in Shanghai, China. Urinary levels of PheT, total NNAL, and total cotinine were significantly higher in cases than controls (N = 476 matched pairs). ORs (95% confidence intervals) for lung cancer in the second, third, fourth, and fifth quintiles of PheT were 1.70 (1.00-2.88), 1.07 (0.62-1.84), 1.48 (0.86-2.53), and 2.34 (1.33-4.11), respectively, relative to the lowest quartile (Ptrend = 0.023) after adjustment for self-reported smoking intensity and duration and urinary total NNAL and total cotinine. This study also confirmed that urinary total NNAL and total cotinine are independently related to lung cancer risk.

Original languageEnglish (US)
Pages (from-to)6749-6757
Number of pages9
JournalCancer Research
Volume71
Issue number21
DOIs
StatePublished - Nov 1 2011

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