Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers: The Multiethnic Cohort Study.

Abstract

BACKGROUND:

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.

• Authors: Shannon S Cigan, Sharon E Murphy, Daniel O Stram, Stephen S Hecht, Loïc Le Marchand, Irina Stepanov, Sungshim L Park
• Journal: Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology (Cancer Epidemiol Biomarkers Prev) Vol. 32 Issue 3 Pg. 306-314 (03 06 2023) ISSN: 1538-7755 [Electronic] United States
• PMID: 36350738 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: ©2022 American Association for Cancer Research.

Chemical References

• Cotinine
• hydroxypropyl methacrylate
• Cadmium
• Biomarkers
• Nitrosamines

Topics

• Humans
• Cohort Studies
• Cotinine
• Incidence
• Smokers
• Cadmium
• Biomarkers (urine)
• Cigarette Smoking
• Lung Neoplasms (etiology)
• Nitrosamines (urine)