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. 2020 Oct 29;22(11):2109-2113.
doi: 10.1093/ntr/ntaa117.

Relationships Between Race, Gender, and Spot Urine Levels of Biomarkers of Tobacco Exposure Vary Based on How Creatinine Is Handled in Analyses

Dana M Carroll  1   2 , Shannon Cigan  3 , Joshua Ikuemonisan  2 , Taylor Hammonds  4 , Irina Stepanov  1   2 , Gideon St Helen  5 , Neal Benowitz  5 , Dorothy K Hatsukami  2   6
Affiliations

Relationships Between Race, Gender, and Spot Urine Levels of Biomarkers of Tobacco Exposure Vary Based on How Creatinine Is Handled in Analyses

Dana M Carroll et al. Nicotine Tob Res. .

Abstract

Introduction: We illustrate the differential impact of common analysis approaches to handling urinary creatinine, a measure for urine dilution, on relationships between race, gender, and biomarkers of exposure measured in spot urine.

Methods: In smokers, spot urine levels of total nicotine equivalents (TNE, sum of total nicotine, total cotinine, and total 3'-hydroxycotinine) and total 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) overall and per cigarette were examined. Relationships between race (African Americans [AA] n = 373, Whites n = 758) or gender (males n = 629, females n = 502) and TNE or NNAL were examined using the following approaches to handling creatinine: (1) unadjusted/unstandardized; (2) standardization; (3) adjustment as a covariate. Significance was considered at p < .05.

Results: Creatinine was higher in AA versus Whites (1.19 vs. 0.96 mg/mL; p < .0001) and in males versus females (1.21 vs. 0.84 mg/mL; p < .0001). Independent of how creatinine was handled, TNE was lower among AA than Whites (TNE ratios AA vs. Whites: 0.67-0.84; p's < .05). Unadjusted TNE per cigarette was higher among AA versus Whites (ratio 1.12; p = .0411); however, the relationship flipped with standardization (ratio 0.90; p = .0360) and adjustment (ratio 0.95; p = .3165). Regarding gender, unadjusted TNE was higher among males versus females (ratio 1.13; p = .0063), but the relationship flipped with standardization (ratio 0.79; p < .0001) or adjustment (ratio 0.89; p = .0018). Unadjusted TNE per cigarette did not differ across gender (ratio 0.98; p = .6591), but lower levels were found in males versus females with standardization (ratio 0.68; p < .0001) and adjustment (ratio 0.74; p < .0001). NNAL displayed similar patterns.

Conclusions: Relationships between race, gender, and spot urine levels of biomarkers of exposure can vary greatly based on how creatinine is handled in analyses.

Implications: Lack of appropriate methods can lead to discrepancies across reports on variability of urinary biomarkers by race and gender. We recommend that for any analyses of biomarkers of exposure measure in spot urine samples across race, gender, or other population subgroups that differ in urinary creatinine levels, sensitivity analyses comparing the different methods for handling urinary creatinine should be conducted. If methods result in discrepant findings, this should be clearly noted and discussed.

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Figures

Figure 1.
Figure 1.
Distribution of log-transformed urinary creatinine (natural log of mg/mL) by race and gender in spot urine sample among cigarette smokers.
See this image and copyright information in PMC

References

    1. Chang CM, Edwards SH, Arab A, Del Valle-Pinero AY, Yang L, Hatsukami DK. Biomarkers of tobacco exposure: summary of an FDA-sponsored public workshop. Cancer Epidemiol Biomarkers Prev. 2017;26(3):291–302. - PMC - PubMed
    1. United States Department of Health and Human Services. National Institutes of Health. National Institute on Drug Abuse, and United States Department of Health and Human Services. Food and Drug Administration. Center for Tobacco Products. Population Assessment of Tobacco and Health (PATH) Study [United States] Restricted-Use Files. Inter-university Consortium for Political and Social Research [distributor], 2020-06-24.
    1. Barr DB, Wilder LC, Caudill SP, Gonzalez AJ, Needham LL, Pirkle JL. Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements. Environ Health Perspect. 2005;113(2):192–200. - PMC - PubMed
    1. Carroll DM, Wagener TL, Peck JD, et al. . Biomarkers of exposure in ENDS users, smokers, and dual users of American Indian descent. Tob Regul Sci. 2018;4(2):3–15. - PMC - PubMed
    1. St Helen G, Dempsey D, Wilson M, Jacob P 3rd, Benowitz NL. Racial differences in the relationship between tobacco dependence and nicotine and carcinogen exposure. Addiction. 2013;108(3):607–617. - PMC - PubMed

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