A Prospectively Measured Serum Biomarker for a Tobacco-Specific Carcinogen and Lung Cancer in Smokers

被引:95
作者
Church, Timothy R. [1 ,4 ]
Anderson, Kristin E. [2 ,4 ]
Caporaso, Neil E. [5 ]
Geisser, Mindy S. [1 ]
Le, Chap T. [3 ,4 ]
Zhang, Yan [4 ]
Benoit, Adam R. [4 ]
Carmella, Steven G. [4 ]
Hecht, Stephen S. [4 ]
机构
[1] Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Sch Publ Hlth, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Mason Canc Ctr, Minneapolis, MN USA
[5] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA
关键词
PHENANTHRENE METABOLITE RATIOS; DNA-ADDUCTS; PULMONARY NEOPLASIA; EXPOSURE; SMOKING; RISK; R-1,T-2,3,C-4-TETRAHYDROXY-1,2,3,4-TETRAHYDROPHENANTHRENE; TUMORIGENESIS; PROGRESSION; INHIBITION;
D O I
10.1158/1055-9965.EPI-08-0718
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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. Findings: 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. (Cancer Epidemiol Biomarkers Prev 2009;18(1):260-6)
引用
收藏
页码:260 / 266
页数:7
相关论文
共 36 条
[1]  
[Anonymous], 2004, Tobacco smoke and involuntary smoking. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans, V83, P53
[2]  
[Anonymous], 2009, Modern epidemiology
[3]  
[Anonymous], 2004, IARC monographs on the evaluation of carcinogenic risks to humans, V83, P1179
[4]  
BELINSKY SA, 1990, CANCER RES, V50, P3772
[5]  
BENOWITZ NL, 1994, J PHARMACOL EXP THER, V268, P296
[6]   Serum cotinine level as predictor of lung cancer risk [J].
Boffetta, Paolo ;
Clark, Sarah ;
Shen, Min ;
Gislefoss, Randi ;
Peto, Richard ;
Andersen, Aage .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2006, 15 (06) :1184-1188
[7]   Combined analysis of r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol in smokers' plasma [J].
Carmella, Steven G. ;
Yoder, Andrea ;
Hecht, Stephen S. .
CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION, 2006, 15 (08) :1490-1494
[8]   Phenethyl isothiocyanate and sulforaphane and their N-acetylcysteine conjugates inhibit malignant progression of lung adenomas induced by tobacco carcinogens in A/J mice [J].
Conaway, CC ;
Wang, CX ;
Pittman, B ;
Yang, YM ;
Schwartz, JE ;
Tian, DF ;
McIntee, EJ ;
Hecht, SS ;
Chung, FL .
CANCER RESEARCH, 2005, 65 (18) :8548-8557
[9]   The Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial of the National Cancer Institute: History, organization, and status [J].
Gohagan, JK ;
Prorok, PC ;
Hayes, RB ;
Kramer, BS .
CONTROLLED CLINICAL TRIALS, 2000, 21 (06) :251S-272S
[10]   Causal diagrams for epidemiologic research [J].
Greenland, S ;
Pearl, J ;
Robins, JM .
EPIDEMIOLOGY, 1999, 10 (01) :37-48