{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:32:38Z","timestamp":1786354358885,"version":"build-2736575974"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"8","funder":[{"DOI":"10.13039\/100010628","name":"Center for Tobacco Products","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000038","name":"Food and Drug Administration","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000016","name":"Department of Health and Human Services","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000016","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010628","name":"Center for Tobacco Products","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010628","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000030","name":"Centers for Disease Control and Prevention","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000030","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["Z01-ES044005"],"award-info":[{"award-number":["Z01-ES044005"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The constituents of tobacco smoke that specifically contribute to lung cancer risk have yet to be fully identified. We evaluated associations between biomarkers of potentially harmful constituents\u2014polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, nicotine, and volatile organic compounds\u2014and lung cancer incidence among US women.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In a case-cohort study nested within the Sister Study (women aged 35-74\u2009years at baseline, enrolled 2003-2009), data were obtained for a random subcohort and all remaining incident lung cancers through September 2017 (median follow-up = 9.6\u2009years), stratified by race and ethnicity (Hispanic, non-Hispanic Black, non-Hispanic White, others) and smoking status (current, former, never). The analytic sample included 356 cases and 433 noncases. We quantified 30 biomarkers in baseline urine samples and calculated hazard ratios (HRs) for associations between 1-unit increase in biomarker concentrations (log-scale) and lung cancer incidence using weighted Cox regression models adjusted for urinary creatinine and demographic, health, and lifestyle factors.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among women who were currently smoking at enrollment, positive associations were observed for biomarkers of polycyclic aromatic hydrocarbons (naphthalene, phenanthrene, pyrene, fluorene; HRs = 1.4-5.3), tobacco-specific nitrosamines (particularly 4-[methylnitrosamino]-1-[3-pyridyl]-1-butanone [nicotine-derived nitrosamine ketone]; HRs = 1.3-2.2), and volatile organic compounds (xylene, acrylamide, acrylonitrile, 1,2-dibromoethane and\/or vinyl-chloride and\/or ethylene-oxide and\/or acrylonitrile, acrolein, styrene and\/or ethylbenzene, benzene, dimethylformamide and\/or methylisocyanate, 1,3-butadiene, crotonaldehyde, isoprene; HRs = 1.6-4.4). Associations with biomarkers of most polycyclic aromatic hydrocarbons, nicotine-derived nitrosamine ketone, xylene, and dimethylformamide and\/or methylisocyanate remained after additional adjustment for smoking frequency, duration, and nicotine metabolites. In women who did not smoke, positive associations were observed for styrene and\/or ethylbenzene and dimethylformamide and\/or methylisocyanate biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Exposure to polycyclic aromatic hydrocarbons, tobacco-specific nitrosamines, and several volatile organic compounds through tobacco smoking were associated with increased lung cancer risk among women.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djag078","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:38:24Z","timestamp":1773855504000},"page":"1444-1452","source":"Crossref","is-referenced-by-count":0,"title":["Tobacco-related urinary biomarkers and lung cancer risk in women, a case-cohort analysis"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7464-9756","authenticated-orcid":false,"given":"Mahdi","family":"Nalini","sequence":"first","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1931-1349","authenticated-orcid":false,"given":"Katie M","family":"O\u2019Brien","sequence":"additional","affiliation":[{"name":"Epidemiology Branch, National Institute of Environmental Health Sciences , Research Triangle Park, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9796-7482","authenticated-orcid":false,"given":"Antonia M","family":"Calafat","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6620-7096","authenticated-orcid":false,"given":"Lanqing","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2582-9483","authenticated-orcid":false,"given":"Jun","family":"Feng","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7613-6831","authenticated-orcid":false,"given":"Christopher M","family":"Reese","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5081-7447","authenticated-orcid":false,"given":"Baoyun","family":"Xia","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julianne Cook","family":"Botelho","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5089-0855","authenticated-orcid":false,"given":"Yuesong","family":"Wang","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4702-1525","authenticated-orcid":false,"given":"Tiffany","family":"Seyler","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3349-9827","authenticated-orcid":false,"given":"Esther J","family":"Roh","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Food and Drug Administration , Silver Spring, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-1783-4932","authenticated-orcid":false,"given":"Nicole A","family":"Tashakkori","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Food and Drug Administration , Silver Spring, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6835-9163","authenticated-orcid":false,"given":"Aaron","family":"Blakney","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Food and Drug Administration , Silver Spring, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4230-4980","authenticated-orcid":false,"given":"Kerui","family":"Xu","sequence":"additional","affiliation":[{"name":"Division for Heart Disease and Stroke Prevention, National Center for Chronic Disease Prevention and Health Promotion, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell H","family":"Gail","sequence":"additional","affiliation":[{"name":"Biostatistics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4788-8169","authenticated-orcid":false,"given":"Benjamin C","family":"Blount","sequence":"additional","affiliation":[{"name":"Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention , Atlanta, GA,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-8222","authenticated-orcid":false,"given":"Cindy M","family":"Chang","sequence":"additional","affiliation":[{"name":"Center for Tobacco Products, Food and Drug Administration , Silver Spring, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3008-7843","authenticated-orcid":false,"given":"Christian C","family":"Abnet","sequence":"additional","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6776-0018","authenticated-orcid":false,"given":"Dale P","family":"Sandler","sequence":"additional","affiliation":[{"name":"Epidemiology Branch, National Institute of Environmental Health Sciences , Research Triangle Park, NC,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0074-1098","authenticated-orcid":false,"given":"Neal D","family":"Freedman","sequence":"additional","affiliation":[{"name":"Tobacco Control Research Branch, Division of Cancer Control and Population Sciences, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-1072","authenticated-orcid":false,"given":"Arash","family":"Etemadi","sequence":"additional","affiliation":[{"name":"Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health , Bethesda, MD,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026081005031811400_djag078-B1","first-page":"405","article-title":"Proportion and number of cancer cases and deaths attributable to potentially modifiable risk factors in the United States, 2019","volume":"74","author":"Islami","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2026081005031811400_djag078-B2","doi-asserted-by":"crossref","first-page":"113179","DOI":"10.1016\/j.fct.2022.113179","article-title":"Carcinogenic components of tobacco and tobacco smoke: a 2022 update","volume":"165","author":"Li","year":"2022","journal-title":"Food Chem Toxicol"},{"key":"2026081005031811400_djag078-B3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1158\/0008-5472.CAN-13-3178","article-title":"Urinary tobacco smoke-constituent biomarkers for assessing risk of lung cancer","volume":"74","author":"Yuan","year":"2014","journal-title":"Cancer Res"},{"key":"2026081005031811400_djag078-B4","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1158\/1055-9965.EPI-22-1289","article-title":"Biomarkers of tobacco carcinogenesis in diverse populations: challenges and opportunities","volume":"32","author":"Etemadi","year":"2023","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081005031811400_djag078-B5","doi-asserted-by":"crossref","first-page":"127003","DOI":"10.1289\/EHP1923","article-title":"The sister study cohort: baseline methods and participant characteristics","volume":"125","author":"Sandler","year":"2017","journal-title":"Environ Health Perspect"},{"key":"2026081005031811400_djag078-B6","doi-asserted-by":"crossref","first-page":"804","DOI":"10.3390\/ijerph15040804","article-title":"Urinary cotinine concentration and self-reported smoking status in 1075 subjects living in Central Italy","volume":"15","author":"Paci","year":"2018","journal-title":"Int J Environ Res Public Health"},{"key":"2026081005031811400_djag078-B7","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1016\/S0895-4356(99)00102-X","article-title":"Analysis of case-cohort designs","volume":"52","author":"Barlow","year":"1999","journal-title":"J Clin Epidemiol"},{"key":"2026081005031811400_djag078-B8","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1097\/EDE.0000000000001469","article-title":"The case for case-cohort: an applied epidemiologist\u2019s guide to reframing case-cohort studies to improve usability and flexibility","volume":"33","author":"O\u2019Brien","year":"2022","journal-title":"Epidemiology"},{"key":"2026081005031811400_djag078-B9","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1289\/ehp.7337","article-title":"Urinary creatinine concentrations in the U.S. population: implications for urinary biologic monitoring measurements","volume":"113","author":"Barr","year":"2005","journal-title":"Environ Health Perspect"},{"key":"2026081005031811400_djag078-B10","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1158\/1055-9965.EPI-18-0743","article-title":"Urinary biomarkers of carcinogenic exposure among cigarette, waterpipe, and smokeless tobacco users and never users of tobacco in the Golestan cohort study","volume":"28","author":"Etemadi","year":"2019","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081005031811400_djag078-B11","doi-asserted-by":"crossref","first-page":"2109","DOI":"10.1093\/ntr\/ntaa117","article-title":"Relationships between race, gender, and spot urine levels of biomarkers of tobacco exposure vary based on how creatinine is handled in analyses","volume":"22","author":"Carroll","year":"2020","journal-title":"Nicotine Tob Res"},{"key":"2026081005031811400_djag078-B12","author":"International agency for research on cancer","year":"2024"},{"key":"2026081005031811400_djag078-B13","doi-asserted-by":"crossref","first-page":"6749","DOI":"10.1158\/0008-5472.CAN-11-0209","article-title":"Urinary levels of cigarette smoke constituent metabolites are prospectively associated with lung cancer development in smokers","volume":"71","author":"Yuan","year":"2011","journal-title":"Cancer Res"},{"key":"2026081005031811400_djag078-B14","doi-asserted-by":"crossref","first-page":"1073","DOI":"10.1158\/1055-9965.EPI-23-1362","article-title":"Association of urinary biomarkers of tobacco exposure with lung cancer risk in African American and white cigarette smokers in the southern community cohort study","volume":"33","author":"Murphy","year":"2024","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081005031811400_djag078-B15","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1158\/1055-9965.EPI-22-0569","article-title":"Association of urinary biomarkers of smoking-related toxicants with lung cancer incidence in smokers: the multiethnic cohort study","volume":"32","author":"Cigan","year":"2023","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081005031811400_djag078-B16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1158\/1055-9965.EPI-08-0718","article-title":"A prospectively measured serum biomarker for a tobacco-specific carcinogen and lung cancer in smokers","volume":"18","author":"Church","year":"2009","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"2026081005031811400_djag078-B17","doi-asserted-by":"crossref","first-page":"118077","DOI":"10.1016\/j.envpol.2021.118077","article-title":"Associations of polycyclic aromatic hydrocarbons exposure and its interaction with XRCC1 genetic polymorphism with lung cancer: a case-control study","volume":"290","author":"Zhou","year":"2021","journal-title":"Environ Pollut"},{"key":"2026081005031811400_djag078-B18","author":"The Center for Disease Control and Prevention","year":"2025"},{"key":"2026081005031811400_djag078-B19","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1021\/acs.accounts.5b00472","article-title":"Exposure and metabolic activation biomarkers of carcinogenic tobacco-specific nitrosamines","volume":"49","author":"Hecht","year":"2016","journal-title":"Acc Chem Res"},{"key":"2026081005031811400_djag078-B20","doi-asserted-by":"crossref","first-page":"2990","DOI":"10.1158\/0008-5472.CAN-08-4330","article-title":"Urinary levels of tobacco-specific nitrosamine metabolites in relation to lung cancer development in two prospective cohorts of cigarette smokers","volume":"69","author":"Yuan","year":"2009","journal-title":"Cancer Res"},{"key":"2026081005031811400_djag078-B21","doi-asserted-by":"crossref","first-page":"611674","DOI":"10.3389\/fonc.2021.611674","article-title":"Relationship between urinary 4-(Methylnitrosamino)-1-(3-Pyridyl)-1-butanol and lung cancer risk in the general population: a community-based prospective cohort study","volume":"11","author":"Park","year":"2021","journal-title":"Front Oncol"},{"key":"2026081005031811400_djag078-B22","author":"The U.S. Food and Drug Administration","year":"2025"},{"key":"2026081005031811400_djag078-B23","author":"International Agency for Research on Cancer","year":"2024"},{"key":"2026081005031811400_djag078-B24","doi-asserted-by":"crossref","first-page":"7349","DOI":"10.3390\/ijerph18147349","article-title":"Associations between biomarkers of exposure and lung cancer risk among exclusive cigarette smokers in the Golestan cohort study","volume":"18","author":"Rostron","year":"2021","journal-title":"Int J Environ Res Public Health"},{"key":"2026081005031811400_djag078-B25","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1093\/carcin\/bgs026","article-title":"Urinary levels of volatile organic carcinogen and toxicant biomarkers in relation to lung cancer development in smokers","volume":"33","author":"Yuan","year":"2012","journal-title":"Carcinogenesis"},{"key":"2026081005031811400_djag078-B26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1186\/s12931-025-03165-1","article-title":"Exposure to volatile organic compounds and chronic respiratory disease mortality, a case-cohort study","volume":"26","author":"Nalini","year":"2025","journal-title":"Respir Res"},{"key":"2026081005031811400_djag078-B27","doi-asserted-by":"crossref","first-page":"345","DOI":"10.3109\/13547501003753881","article-title":"Temporal stability of urinary and plasma biomarkers of tobacco smoke exposure among cigarette smokers","volume":"15","author":"Church","year":"2010","journal-title":"Biomarkers"},{"key":"2026081005031811400_djag078-B28","doi-asserted-by":"crossref","first-page":"778","DOI":"10.1038\/nrc2190","article-title":"Lung cancer in never smokers\u2014a different disease","volume":"7","author":"Sun","year":"2007","journal-title":"Nat Rev Cancer"},{"key":"2026081005031811400_djag078-B29","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1001\/jamaoncol.2020.6362","article-title":"Proportion of never smokers among men and women with lung cancer in 7 US states","volume":"7","author":"Siegel","year":"2021","journal-title":"JAMA Oncol"},{"key":"2026081005031811400_djag078-B30","author":"World Health Organization","year":"2023"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djag078\/67392312\/djag078.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/8\/1444\/67392312\/djag078.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/8\/1444\/67392312\/djag078.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T09:03:26Z","timestamp":1786352606000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/118\/8\/1444\/8527873"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,18]]},"references-count":30,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,3,18]]},"published-print":{"date-parts":[[2026,8,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djag078","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,3,18]]}}}