Exposures to
polycyclic aromatic hydrocarbons (PAHs) from various environmental and occupational sources are considered a primary risk factor for
lung cancer among lifelong never smokers, based largely on results from epidemiologic studies utilizing self-reported exposure information. Prospective,
biomarker-based human studies on the role of PAH and other airborne
carcinogens in the development of
lung cancer among lifelong non-smokers have been lacking. We prospectively investigated levels of urinary metabolites of a PAH and
volatile organic compounds in relation to
lung cancer risk in a nested case-control study of 82 cases and 83 controls among lifelong never smokers of the Shanghai Cohort Study, a prospective cohort of 18 244 Chinese men aged 45-64 years at enrollment. We quantified three PAH metabolites:
r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), 3-hydroxyphenanthrene (3-OH-Phe) and total hydroxyphenanthrenes (total
OH-Phe, the sum of 1-, 2-, 3- and 4-
OH-Phe), as well as metabolites of the
volatile organic compounds acrolein (3-hydroxypropyl
mercapturic acid),
benzene (S-phenyl
mercapturic acid),
crotonaldehyde (3-hydroxy-1-methylpropylmercapturic acid) and
ethylene oxide (2-hydroxyethyl
mercapturic acid). Urinary
cotinine was also quantified to confirm non-smoking status. Compared with the lowest quartile, odds ratios (95% confidence intervals) for
lung cancer risk for the highest quartile levels of PheT, 3-OH-Phe and total
OH-Phe were 2.98 (1.13-7.87), 3.10 (1.12-7.75) and 2.59 (1.01-6.65) (all P trend < 0.05), respectively. None of the metabolites of the
volatile organic compounds were associated with overall
lung cancer risk. This study demonstrates a potentially important role of exposure to PAH in the development of
lung cancer among lifelong never smokers.