TY - JOUR
T1 - Association of Urinary Biomarkers of Smoking-Related Toxicants with Lung Cancer Incidence in Smokers
T2 - The Multiethnic Cohort Study
AU - Cigan, Shannon S.
AU - Murphy, Sharon E.
AU - Stram, Daniel O.
AU - Hecht, Stephen S.
AU - Le Marchand, Loïc
AU - Stepanov, Irina
AU - Park, Sungshim L.
N1 - Publisher Copyright:
© 2022 American Association for Cancer Research.
PY - 2023/3/1
Y1 - 2023/3/1
N2 - 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-(methylni-trosamino)-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.
AB - 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-(methylni-trosamino)-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.
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U2 - 10.1158/1055-9965.EPI-22-0569
DO - 10.1158/1055-9965.EPI-22-0569
M3 - Article
C2 - 36350738
AN - SCOPUS:85149999590
SN - 1055-9965
VL - 32
SP - 306
EP - 314
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 3
ER -
