Affiliation:
1. 1Department of Pediatrics, Division of Epidemiology and Clinical Research, University of Minnesota, Minneapolis, Minnesota.
2. 2Division of Environmental Health Sciences, University of Minnesota, Minneapolis, Minnesota.
3. 3Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.
4. 4Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California.
5. 5Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii.
Abstract
AbstractBackground:While cigarette smoking is the leading cause of lung cancer, the majority of smokers do not develop the disease over their lifetime. The inter-individual differences in risk among smokers may in part be due to variations in exposure to smoking-related toxicants.Methods:Using data from a subcohort of 2,309 current smokers at the time of urine collection from the Multiethnic Cohort Study, we prospectively evaluated the association of ten urinary biomarkers of smoking-related toxicants [total nicotine equivalents (TNE), a ratio of total trans-3′-hydroxycotinine (3-HCOT)/cotinine (a phenotypic measure of CYP2A6 enzymatic activity), 4-(methylnitrosamino)-1–3-(pyridyl)-1-butanol (NNAL), S-phenylmercapturic acid (SPMA), 3-hydroxypropyl mercapturic acid (3-HPMA), phenanthrene tetraol (PheT), 3-hydroxyphenanthrene (PheOH), the ratio of PheT/PheOH, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid (8-iso-PGF2α)] with lung cancer risk (n = 140 incident lung cancer cases over an average of 13.4 years of follow-up). Lung cancer risk was estimated using Cox proportional hazards models.Results:After adjusting for decade of birth, sex, race/ethnicity, body mass index, self-reported pack-years, creatinine, and urinary TNE (a biomarker of internal smoking dose), a one SD increase in log total 3-HCOT/cotinine (HR, 1.33; 95% CI, 1.06–1.66), 3-HPMA (HR, 1.41; 95% CI, 1.07–1.85), and Cd (HR, 1.45; 95% CI, 1.18–1.79) were each associated with increased lung cancer risk.Conclusions:Our study demonstrates that urinary total 3-HCOT/cotinine, 3-HPMA, and Cd are positively associated with lung cancer risk. These findings warrant replication and consideration as potential biomarkers for smoking-related lung cancer risk.Impact:These biomarkers may provide additional information on lung cancer risk that is not captured by self-reported smoking history or TNE.See related commentary by Etemadi et al., p. 289
Funder
National Cancer Institute
National Institute for Occupational Safety and Health
Publisher
American Association for Cancer Research (AACR)