Abstract A6: Urinary levels of volatile organic carcinogens and toxicant biomarkers in relation to lung cancer development in both smokers and nonsmokers: The Shanghai Cohort Study
Authors: Yuan Jian-Min , Gao Yu-Tang , Carmella Steven G. , Wang Renwei , Chen Menglan , Hecht Stephen S. 
Published: June 2012

Background: Benzene and ethylene oxide are considered carcinogenic to humans by International Agency for Research on Cancer based on experimental animal studies whereas acrolein and crotonaldehyde are considered weak carcinogens. They are present in cigarette smoke and other environmental sources. Epidemiological data linking them to lung cancer in humans have been lacking.

Methods: A nested case-control study of lung cancer was conducted within the Shanghai Cohort Study, a population-based prospective cohort of 18,244 Chinese men aged 45–64 years at enrollment during 1986–1989. In addition to in-person interviews for information on use of tobacco and alcohol, usual diet, and medical history, each participant provided a 10-ml blood sample and one single void urine sample at baseline. Annual follow-ups to each surviving subject were conducted to identify incident cancer cases and death. The present study included 96 cases who never smoked and 343 cases who smoked cigarettes at baseline. One control for each case was randomly chosen among cohort participants. The control was matched to the index case by age (±2 years), date of urine collection (±1 month), neighborhood of residence, and smoking status. We quantified urinary mercapturic acid metabolites for benzene [S-phenyl mercapturic acid (SPMA)], ethylene oxide [2-hydroxyethyl mercapturic acid (HEMA)], acrolein [3-hydroxypropyl mercapturic acid (HPMA)], and crotonaldehyde [4-hydroxybut-2-yl mercapturic acid (HBMA)] for all study subjects. For current smokers, we also determined urinary levels of cotinine and its glucuronides (total cotinine), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and its glucuronides (PheT), validated biomarkers of uptake and metabolism of nicotine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and polycyclic aromatic hydrocarbons (PAH), respectively, for current smokers. The odds ratio (OR) and 95% confidence interval (CI) for lung cancer with urinary biomarkers were estimated using an unconditional logistic regression method.

Results: Among current smokers, all measured mercapturic acid metabolites were statistically significantly higher in cases than controls. Compared with the lowest quartile, ORs (95% CIs) of lung cancer for highest quartile were 1.80 (1.14–2.85) for SPMA, 2.13 (1.34–3.37) for HEMA, 2.00 (1.25–3.20) for HPMA, and 1.95 (1.22–3.12) for HBMA (all P's for trend &lt;0.01). Further adjustment for urinary total cotinine, total NNAL, and PheT significantly attenuated and resulted in a null association between all mercapturic acid metabolites and lung cancer risk (all P's for trend &gt;0.50). Among never smokers, cases showed elevated levels of SPMA, but similar levels of HEMA, HPMA, and HBMA, compared with controls. OR for lung cancer was 2.11 (95% CI 1.05–4.23) for highest tertile of SPMA (P for trend = 0.026). There was no statistically significant association between urinary HEMA, HPMA or HBMA and lung cancer risk among never smokers.

Conclusion: Urinary SPMA, a mercapturic acid metabolite for benzene, is statistically significant associated with lung cancer risk among never smokers whereas this positive association among current smokers could be largely explained by urinary biomarkers for nicotine, NNK and PAH, established risk factors for lung cancer for smokers in the present study population. Mercapturic acid metabolites for acrolein, crotonaldehyde, and ethylene oxide are not independent predictors for lung cancer for both smokers and nonsmokers.

Citation Information: Cancer Prev Res 2011;4(10 Suppl):A6.