Association of Urinary Biomarkers of Tobacco Exposure with Lung Cancer Risk in African American and White Cigarette Smokers in the Southern Community Cohort Study

Author:

Murphy Sharon E.12ORCID,Guillermo Cherie3ORCID,Thomson Nicole M.2ORCID,Carmella Steven G.2ORCID,Wittmann Milo2ORCID,Aldrich Melinda C.4ORCID,Cai Qiuyin5ORCID,Sullivan Shannon M.2ORCID,Stram Daniel O.6ORCID,Le Marchand Loïc3ORCID,Hecht Stephen S.2ORCID,Blot William J.5ORCID,Park S. Lani3ORCID

Affiliation:

1. Department of Biochemistry Molecular Biology and Biophysics, University of Minnesota, Minneapolis, Minnesota. 1

2. Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota. 2

3. Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii. 3

4. Division of Genetic Medicine, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. 4

5. Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, Tennessee. 5

6. Department of Preventive Medicine, Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California. 6

Abstract

Abstract Background: After accounting for smoking history, lung cancer incidence is greater in African Americans than Whites. In the multiethnic cohort, total nicotine equivalents (TNE) are higher in African Americans than Whites at similar reported cigarettes per day. Greater toxicant uptake per cigarette may contribute to the greater lung cancer risk of African Americans. Methods: In a nested case–control lung cancer study within the Southern Community Cohort, smoking-related biomarkers were measured in 259 cases and 503 controls (40% White; 56% African American). TNE, the trans-3-hydroxycotinine/cotinine ratio, 4-(methylnitrosamino)-1–3-(pyridyl)-1-butanol (NNAL), mercapturic acid metabolites of volatile organic compounds, phenanthrene metabolites, cadmium (Cd), and (Z)-7-(1R,2R,3R,5S)-3,5-dihydroxy-2-[(E,3S)-3-hydroxyoct-1-enyl]cyclopenyl]hept-5-enoic acid were quantified in urine. Unconditional logistic regression was used to estimate the ORs and 95% confidence intervals (CI) for each biomarker and lung cancer risk. Results: TNE, NNAL, and Cd were higher in cases than controls (adjusted for age, race, sex, body mass index, and cigarettes per day). Among cases, these levels were higher in African Americans compared with Whites. After accounting for age, sex, body mass index, and pack-years, a one-SD increase in log-TNE (OR = 1.30; 95% CI, 1.10–1.54) and log-NNAL (OR = 1.27; 95% CI, 1.03–1.58 with TNE adjustment) was associated with lung cancer risk. In this study, in which NNAL concentration is relatively high, the association for log-TNE was attenuated after adjustment for log-NNAL. Conclusions: Smoking-related biomarkers provide additional information for lung cancer risk in smokers beyond smoking pack-years. Impact: Urinary NNAL, TNE, and Cd concentrations in current smokers, particularly African American smokers, may be useful for predicting lung cancer risk.

Funder

National Cancer Institute

Publisher

American Association for Cancer Research (AACR)

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