Abstract 1502: Urinary biomarkers of polycyclic aromatic hydrocarbon and volatile organic carcinogens in relation to lung cancer development in lifelong never smokers - The Shanghai Cohort Study.
Authors: Yuan Jian-Min , Gao Yu-Tang , Murphy Sharon , Carmella Steven G. , Wang Renwei , Nelson Heather H. , Hecht Stephen S. 
Published: August 2014

Background: In the United States, 10-15% of lung cancer victims are lifelong never smokers. Non-smoking related lung cancer alone ranks as the 6th most frequently diagnosed cancer. The etiological factors for non-smoking lung cancer are unclear. Although strong evidence supports a major role for polycyclic aromatic hydrocarbon (PAH) as causes of lung cancer in smokers, epidemiological studies prospectively investigating biomarkers of PAH and volatile organic carcinogens in relation to lung cancer risk among never smokers are lacking.

Methods: A nested case-control study of lung cancer among never smokers was conducted within the Shanghai Cohort Study, a prospective cohort of 18,244 Chinese men aged 45-64 years at enrollment during 1986-1989. After more than 20 years of follow-up, we identified 96 incident lung cancer cases among never smokers. For each case, we randomly chose one control among cohort participants who were never smokers. The control was matched to the index case by age (±2 years), date of urine collection (±1 month) and neighborhood of residence. We quantified urinary free cotinine, 3-hydroxyphenanthrene (3-OH-Phe), total hydroxyphenanthrenes (the sum of 1-, 2-, 3-, and 4-OH-Phe) (total OH-Phe), r-1,t-2,3,c-4-tetrahdroxy-1,2,3,4-tetrahydrophenanthrene (PheT), mercapturic acid metabolites of acrolein [3-hydroxypropyl mercapturic acid (HPMA)], benzene [S-phenyl mercapturic acid (SPMA)], crotonaldehyde [4-hydroxybut-2-yl mercapturic acid (HBMA)], and ethylene oxide [2-hydroxyethyl mercapturic acid (HEMA)]. Self-reported never smokers whose urinary free cotinine was greater than 20 ng/ml were excluded from the present analysis for their potential use of tobacco. The odds ratio (OR) and 95% confidence interval (CI) for lung cancer for each urinary biomarker was estimated using an unconditional logistic regression method.

Results: Among never smokers, urinary levels of all 3 measured PAH biomarkers were statistically significantly higher in cases than controls. The geometric means (pmol/mg creatinine) of total OH-Phe, 3-OH-Phe and PheT were 19.10 (in cases) vs 16.08 (in controls) (P = 0.017); 6.64 vs 5.44 (P = 0.011); and 19.84 vs 16.10 (P = 0.035), respectively. Compared with the lowest quartile, ORs (95% CIs) for lung cancer for the highest quartile were 2.59 (1.01-6.65) for total OH-Phe, 3.10 (1.12-7.75) for 3-OH-Phe, and 2.98 (1.13-7.87) for PheT (all Ptrend &lt;0.05). There was no statistically significant difference in urinary levels of HPMA, SPMA, HBMA and HEMA between cases and controls.

Conclusion: This is the first prospective study that demonstrates a positive association between urinary biomarkers of PAH and lung cancer risk among never smokers. Given its ubiquitous presence in the environment, PAH could account for large proportion of non-smoking related lung cancer.

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Citation Format: Jian-Min Yuan, Yu-Tang Gao, Sharon Murphy, Steven G. Carmella, Renwei Wang, Heather H. Nelson, Stephen S. Hecht. Urinary biomarkers of polycyclic aromatic hydrocarbon and volatile organic carcinogens in relation to lung cancer development in lifelong never smokers - The Shanghai Cohort Study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1502. doi:10.1158/1538-7445.AM2013-1502