A prospectively measured serum biomarker for a tobacco-specific carcinogen and lung cancer in smokers.
BACKGROUND
No prior studies have related a tobacco-specific carcinogen to the risk of lung cancer in smokers. Of the over 60 known carcinogens in cigarette smoke, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is specific to tobacco and causes lung cancer in laboratory animals. Its metabolites, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), have been studied as biomarkers of exposure to NNK. We studied the relation of prospectively measured NNK biomarkers to lung cancer risk.


METHODS
In a case-control study nested in the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial, we randomly selected 100 lung cancer cases and 100 controls who smoked at baseline and analyzed their baseline serum for total NNAL, cotinine, and r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbon exposure and metabolic activation. To examine the association of the biomarkers with all lung cancers and for histologic subtypes, we computed odds ratios for total NNAL, PheT, and cotinine using logistic regression to adjust for potential confounders.


RESULTS
Individual associations of age, smoking duration, and total NNAL with lung cancer risk were statistically significant. After adjustment, total NNAL was the only biomarker significantly associated with risk (odds ratio, 1.57 per unit SD increase; 95% confidence interval, 1.08-2.28). A similar statistically significant result was obtained for adenocarcinoma risk, but not for nonadenocarcinoma.


CONCLUSIONS
This first reporting of the effect of the prospectively measured tobacco-specific biomarker total NNAL, on risk of lung cancer in smokers provides insight into the etiology of smoking-related lung cancer and reinforces targeting NNK for cancer prevention.
Church
Timothy R
TR
Division of Environmental Health Sciences, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA. trc@cccs.umn.edu
Anderson
Kristin E
KE
Caporaso
Neil E
NE
Geisser
Mindy S
MS
Le
Chap T
CT
Zhang
Yan
Y
Benoit
Adam R
AR
Carmella
Steven G
SG
Hecht
Stephen S
SS
D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005965:Glucuronates / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008175:Lung Neoplasms / Q000097:blood* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009602:Nitrosamines / Q000097:blood* / Q000378:metabolism*; D011446:Prospective Studies; D011725:Pyridines / Q000097:blood*; D012307:Risk Factors; D014026:Nicotiana
C099564:4-((methylnitrosoamino)-1-(3-pyridyl)but-1-yl)beta-omega-glucosiduronic acid; D014408:Biomarkers, Tumor; D005965:Glucuronates; D009602:Nitrosamines; D011725:Pyridines; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; C099565:4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol