Urinary levels of cigarette smoke constituent metabolites are prospectively associated with lung cancer development in smokers.
Polycyclic aromatic hydrocarbons (PAH) are believed to be among 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 (P(trend) = 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.
Masonic Cancer Center, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA. yuanj@upmc.edu
Jian-Min
JM
Yuan
Yu-Tang
YT
Gao
Sharon E
SE
Murphy
Steven G
SG
Carmella
Renwei
R
Wang
Yan
Y
Zhong
Kristin A
KA
Moy
Andrew B
AB
Davis
Li
L
Tao
Menglan
M
Chen
Shaomei
S
Han
Heather H
HH
Nelson
Mimi C
MC
Yu
Stephen S
SS
Hecht
D000368:Aged; D002681:China / Q000453:epidemiology; D003367:Cotinine / Q000652:urine*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000209:etiology / Q000652:urine*; D008297:Male; D008875:Middle Aged; D009538:Nicotine / Q000493:pharmacokinetics; D009602:Nitrosamines / Q000493:pharmacokinetics / Q000652:urine*; D010616:Phenanthrenes / Q000652:urine*; D011446:Prospective Studies; D011725:Pyridines / Q000652:urine*; D012906:Smoke / Q000009:adverse effects / Q000032:analysis*; D012907:Smoking / Q000009:adverse effects*; D014026:Nicotiana
D009602:Nitrosamines; D010616:Phenanthrenes; D011725:Pyridines; D012906:Smoke; C502234:r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol; D003367:Cotinine