{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T00:31:42Z","timestamp":1759969902977,"version":"build-2065373602"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T00:00:00Z","timestamp":1756425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01CA202979"],"award-info":[{"award-number":["U01CA202979"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006545","name":"National Institute on Minority Health and Health Disparities","doi-asserted-by":"publisher","award":["R01MD015396"],"award-info":[{"award-number":["R01MD015396"]}],"id":[{"id":"10.13039\/100006545","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021671","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R03CA273625"],"award-info":[{"award-number":["R03CA273625"]}],"id":[{"id":"10.13039\/501100021671","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007208","name":"Vanderbilt-Ingram Cancer Center","doi-asserted-by":"publisher","award":["P30CA068485"],"award-info":[{"award-number":["P30CA068485"]}],"id":[{"id":"10.13039\/100007208","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Previous studies have linked liver diseases to lung cancer (LC) risk; however, few studies evaluated the associations of circulating liver enzyme levels with LC risk. We conducted a study of 353 incident LC cases and 646 matched controls with baseline serum alanine aminotransferase (ALT) and of 548 cases and 1032 matched controls with baseline serum alkaline phosphatase (ALP) nested within the Southern Community Cohort Study. Conditional logistic regression and generalized linear models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) among all study participants and by stratification of potential effect modifiers. Most participants had clinically normal liver enzyme levels. Higher serum ALT levels were associated with reduced LC risk. Compared with the lowest tertile, participants in the second and third tertiles had OR (95% CI) of 0.74 (0.48\u20131.14) and 0.47 (0.28\u20130.78) (Ptrend &amp;lt; .01), respectively. The inverse association was observed in African Americans (AAs) and European Americans, which was especially prominent among men, and was seen in both those diagnosed within [ORT3 versus T1 = 0.41 (0.19\u20130.88)] and beyond [ORT3 versus T1 = 0.35 (0.17\u20130.73)] a median follow-up time of 39 months. Higher serum ALP levels were associated with increased LC risk among AA men only [ORT3 versus T1 = 2.01 (1.19\u20133.39)] (Ptrend &amp;lt; .01). Our results indicate that in a predominantly low-income American population, higher serum ALT levels may be related to lower LC risk. Further studies are warranted to confirm our findings and elucidate the potential underlying biological mechanisms of the associations.<\/jats:p>","DOI":"10.1093\/carcin\/bgaf052","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T13:42:03Z","timestamp":1756474923000},"source":"Crossref","is-referenced-by-count":0,"title":["Associations of prediagnostic serum liver enzyme levels with lung cancer risk in predominantly low-income African and European Americans"],"prefix":"10.1093","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7798-5720","authenticated-orcid":false,"given":"Shuai","family":"Xu","sequence":"first","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2388-1694","authenticated-orcid":false,"given":"Hui","family":"Cai","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2181-8971","authenticated-orcid":false,"given":"Jie","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5194-0009","authenticated-orcid":false,"given":"Jiajun","family":"Shi","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3580-9830","authenticated-orcid":false,"given":"Regina","family":"Courtney","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6368-2684","authenticated-orcid":false,"given":"Hyung-Suk","family":"Yoon","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]},{"name":"University of Florida Health Cancer Center , Gainesville, FL 32610 ,","place":["United States"]},{"name":"Department of Surgery, College of Medicine, University of Florida , Gainesville, FL 32610 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0711-8314","authenticated-orcid":false,"given":"Xiao-Ou","family":"Shu","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5581-5069","authenticated-orcid":false,"given":"William J","family":"Blot","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1226-070X","authenticated-orcid":false,"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9384-5648","authenticated-orcid":false,"given":"Qiuyin","family":"Cai","sequence":"additional","affiliation":[{"name":"Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center , Nashville, TN 37203 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,8,29]]},"reference":[{"key":"2025100804464585200_bgaf052-B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21830","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2025100804464585200_bgaf052-B2","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","article-title":"Global Cancer Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J Clin"},{"key":"2025100804464585200_bgaf052-B3","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1093\/jnci\/djy206","article-title":"Racial\/ethnic differences in lung cancer incidence in the Multiethnic Cohort Study: an update","volume":"111","author":"Stram","year":"2019","journal-title":"J Natl Cancer Inst"},{"key":"2025100804464585200_bgaf052-B4","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.21037\/tlcr-21-794","article-title":"Racial disparities in histological subtype, stage, tumor grade and cancer-specific survival in lung cancer","volume":"11","author":"Zeng","year":"2022","journal-title":"Transl Lung Cancer Res"},{"key":"2025100804464585200_bgaf052-B5","doi-asserted-by":"publisher","first-page":"2910","DOI":"10.3390\/ijerph19052910","article-title":"Racial disparities in cigarette smoking behaviors and differences stratified by metropolitan area of residence","volume":"19","author":"Arauz","year":"2022","journal-title":"Int J Environ Res Public Health"},{"key":"2025100804464585200_bgaf052-B6","doi-asserted-by":"publisher","first-page":"873805","DOI":"10.3389\/fpubh.2022.873805","article-title":"Association between cancer prevalence and different socioeconomic Strata in the US: the National Health and Nutrition Examination Survey, 1999\u20132018","volume":"10","author":"Wang","year":"2022","journal-title":"Front Public Health"},{"key":"2025100804464585200_bgaf052-B7","doi-asserted-by":"publisher","first-page":"1167","DOI":"10.1038\/s41588-022-01115-x","article-title":"Cross-ancestry genome-wide meta-analysis of 61,047 cases and 947,237 controls identifies new susceptibility loci contributing to lung cancer","volume":"54","author":"Byun","year":"2022","journal-title":"Nat Genet"},{"key":"2025100804464585200_bgaf052-B8","doi-asserted-by":"publisher","first-page":"78044","DOI":"10.18632\/oncotarget.20351","article-title":"Chronic obstructive pulmonary disease and risk of lung cancer: a meta-analysis of prospective cohort studies","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"2025100804464585200_bgaf052-B9","doi-asserted-by":"publisher","first-page":"778","DOI":"10.1136\/gutjnl-2021-324191","article-title":"Non-alcoholic fatty liver disease and increased risk of incident extrahepatic cancers: a meta-analysis of observational cohort studies","volume":"71","author":"Mantovani","year":"2022","journal-title":"Gut"},{"key":"2025100804464585200_bgaf052-B10","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1016\/j.cgh.2010.10.014","article-title":"Increased risk for malignant neoplasms among patients with cirrhosis","volume":"9","author":"Kalaitzakis","year":"2011","journal-title":"Clin Gastroenterol Hepatol"},{"key":"2025100804464585200_bgaf052-B11","doi-asserted-by":"publisher","first-page":"705","DOI":"10.1007\/s00408-020-00365-y","article-title":"Chronic Hepatitis C virus infection is associated with an increased risk of lung cancer: a systematic review and meta-analysis","volume":"198","author":"Ponvilawan","year":"2020","journal-title":"Lung"},{"key":"2025100804464585200_bgaf052-B12","doi-asserted-by":"publisher","first-page":"378","DOI":"10.1165\/rcmb.2014-0195OC","article-title":"The lung-liver axis: a requirement for maximal innate immunity and hepatoprotection during pneumonia","volume":"53","author":"Hilliard","year":"2015","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2025100804464585200_bgaf052-B13","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1165\/rcmb.2015-0250PS","article-title":"The gut-liver-lung axis. Modulation of the innate immune response and its possible role in chronic obstructive pulmonary disease","volume":"54","author":"Young","year":"2016","journal-title":"Am J Respir Cell Mol Biol"},{"key":"2025100804464585200_bgaf052-B14","doi-asserted-by":"publisher","first-page":"e033532","DOI":"10.1136\/bmjopen-2019-033532","article-title":"Circulating liver enzymes and risks of chronic diseases and mortality in the prospective EPIC-Heidelberg case-cohort study","volume":"10","author":"Katzke","year":"2020","journal-title":"BMJ Open"},{"key":"2025100804464585200_bgaf052-B15","doi-asserted-by":"publisher","first-page":"26318","DOI":"10.1038\/s41598-024-78281-x","article-title":"Allometric fat mass index and alanine aminotransferase attenuate the associations of platelet parameters with lung cancer risk","volume":"14","author":"Christakoudi","year":"2024","journal-title":"Sci Rep"},{"key":"2025100804464585200_bgaf052-B16","first-page":"972","article-title":"Southern community cohort study: establishing a cohort to investigate health disparities","volume":"97","author":"Signorello","year":"2005","journal-title":"J Natl Med Assoc"},{"key":"2025100804464585200_bgaf052-B17","doi-asserted-by":"publisher","first-page":"895479","DOI":"10.3389\/fonc.2022.895479","article-title":"Associations of Pre-diagnostic Serum levels of total bilirubin and albumin with lung cancer risk: results from the Southern Community Cohort Study","volume":"12","author":"Yoon","year":"2022","journal-title":"Front Oncol"},{"key":"2025100804464585200_bgaf052-B18","doi-asserted-by":"publisher","first-page":"926","DOI":"10.1111\/dme.12187","article-title":"Liver enzymes, race, gender and diabetes risk: the Atherosclerosis Risk in Communities (ARIC) study","volume":"30","author":"Schneider","year":"2013","journal-title":"Diabet Med"},{"key":"2025100804464585200_bgaf052-B19","doi-asserted-by":"publisher","first-page":"446","DOI":"10.1097\/EDE.0b013e318064630a","article-title":"Analysis of matched case-control data with incomplete Strata: applying longitudinal approaches","volume":"18","author":"Lin","year":"2007","journal-title":"Epidemiology"},{"key":"2025100804464585200_bgaf052-B20","doi-asserted-by":"publisher","first-page":"1121900","DOI":"10.3389\/fendo.2023.1121900","article-title":"Circulating liver function markers and the risk of COPD in the UK Biobank","volume":"14","author":"Du","year":"2023","journal-title":"Front Endocrinol"},{"key":"2025100804464585200_bgaf052-B21","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1038\/s41598-022-05766-y","article-title":"The association between elevated lipid profile and liver enzymes: a study on Bangladeshi adults","volume":"12","author":"Kathak","year":"2022","journal-title":"Sci Rep"},{"key":"2025100804464585200_bgaf052-B22","doi-asserted-by":"publisher","first-page":"e0249299","DOI":"10.1371\/journal.pone.0249299","article-title":"Obesity, insulin resistance and their interaction on liver enzymes","volume":"16","author":"Liu","year":"2021","journal-title":"PLoS One"},{"key":"2025100804464585200_bgaf052-B23","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.jacl.2017.05.004","article-title":"Blood lipids profile and lung cancer risk in a meta-analysis of prospective cohort studies","volume":"11","author":"Lin","year":"2017","journal-title":"J Clin Lipidol"},{"key":"2025100804464585200_bgaf052-B24","doi-asserted-by":"publisher","first-page":"e0177875","DOI":"10.1371\/journal.pone.0177875","article-title":"Obesity, metabolic factors and risk of different histological types of lung cancer: a Mendelian randomization study","volume":"12","author":"Carreras-Torres","year":"2017","journal-title":"PLoS One"},{"key":"2025100804464585200_bgaf052-B25","doi-asserted-by":"publisher","first-page":"1821","DOI":"10.1016\/s0016-5085(03)00395-0","article-title":"Relation of elevated serum alanine aminotransferase activity with iron and antioxidant levels in the United States","volume":"124","author":"Ruhl","year":"2003","journal-title":"Gastroenterology"},{"key":"2025100804464585200_bgaf052-B26","doi-asserted-by":"publisher","first-page":"127060","DOI":"10.1016\/j.jtemb.2022.127060","article-title":"Role of iron biomarkers and iron intakes in lung cancer risk: a systematic review and meta-analysis","volume":"74","author":"Wang","year":"2022","journal-title":"J Trace Elem Med Biol"},{"key":"2025100804464585200_bgaf052-B27","doi-asserted-by":"publisher","first-page":"19213","DOI":"10.1038\/srep19213","article-title":"Selenium exposure and cancer risk: an updated meta-analysis and meta-regression","volume":"6","author":"Cai","year":"2016","journal-title":"Sci Rep"},{"key":"2025100804464585200_bgaf052-B28","doi-asserted-by":"publisher","first-page":"14829","DOI":"10.1038\/s41598-021-94385-0","article-title":"Low alanine aminotransferase as a risk factor for chronic obstructive pulmonary disease in males","volume":"11","author":"Choi","year":"2021","journal-title":"Sci Rep"},{"key":"2025100804464585200_bgaf052-B29","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1002\/ijc.33292","article-title":"Causal relationships between body mass index, smoking and lung cancer: univariable and multivariable Mendelian randomization","volume":"148","author":"Zhou","year":"2021","journal-title":"Int J Cancer"},{"key":"2025100804464585200_bgaf052-B30","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1093\/jnci\/djx286","article-title":"Overall and central obesity and risk of lung cancer: a pooled analysis","volume":"110","author":"Yu","year":"2018","journal-title":"J Natl Cancer Inst"},{"key":"2025100804464585200_bgaf052-B31","doi-asserted-by":"publisher","first-page":"6640","DOI":"10.1038\/s41598-021-86216-z","article-title":"Assessment of the relationship of serum liver enzymes activity with general and abdominal obesity in an urban Bangladeshi population","volume":"11","author":"Ali","year":"2021","journal-title":"Sci Rep"},{"key":"2025100804464585200_bgaf052-B32","doi-asserted-by":"publisher","first-page":"1319","DOI":"10.1016\/j.fertnstert","article-title":"Obesity and androgens: facts and perspectives","volume":"85","author":"Pasquali","year":"2006","journal-title":"Fertil Steril"},{"key":"2025100804464585200_bgaf052-B33","doi-asserted-by":"publisher","first-page":"1291","DOI":"10.1007\/s12325-017-0556-1","article-title":"NAFLD as a sexual dimorphic disease: role of gender and reproductive Status in the development and progression of nonalcoholic fatty liver disease and inherent cardiovascular risk","volume":"34","author":"Ballestri","year":"2017","journal-title":"Adv Ther"},{"key":"2025100804464585200_bgaf052-B34","doi-asserted-by":"publisher","first-page":"707254","DOI":"10.1155\/2015\/707254","article-title":"Serum cytokine of IL-10 and IL-12 in chronic liver disease: the immune and inflammatory response","volume":"2015","author":"El-Emshaty","year":"2015","journal-title":"Dis Markers"},{"key":"2025100804464585200_bgaf052-B35","doi-asserted-by":"publisher","first-page":"1867","DOI":"10.1002\/ijc.33351","article-title":"Circulating liver function markers and colorectal cancer risk: a prospective cohort study in the UK Biobank","volume":"148","author":"He","year":"2021","journal-title":"Int J Cancer"},{"key":"2025100804464585200_bgaf052-B36","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1080\/00365513.2019.1585567","article-title":"Relationship between serum alkaline phosphatase level, C-reactive protein and leukocyte counts in adults aged 60 years or older","volume":"79","author":"Seo","year":"2019","journal-title":"Scand J Clin Lab Invest"},{"key":"2025100804464585200_bgaf052-B37","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.lungcan.2013.04.001","article-title":"Bone mass density, fracture history, self-reported osteoporosis as proxy variables for estrogen and the risk of non-small-cell lung cancer\u2013a population based cohort study, the HUNT study: are proxy variables friends or faults?","volume":"81","author":"Hatlen","year":"2013","journal-title":"Lung Cancer"}],"container-title":["Carcinogenesis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/carcin\/advance-article-pdf\/doi\/10.1093\/carcin\/bgaf052\/64161738\/bgaf052.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/46\/3\/bgaf052\/64161738\/bgaf052.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/carcin\/article-pdf\/46\/3\/bgaf052\/64161738\/bgaf052.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T08:46:52Z","timestamp":1759913212000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/carcin\/article\/doi\/10.1093\/carcin\/bgaf052\/8244081"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,29]]},"references-count":37,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,9,4]]}},"URL":"https:\/\/doi.org\/10.1093\/carcin\/bgaf052","relation":{},"ISSN":["0143-3334","1460-2180"],"issn-type":[{"type":"print","value":"0143-3334"},{"type":"electronic","value":"1460-2180"}],"subject":[],"published-other":{"date-parts":[[2025,9]]},"published":{"date-parts":[[2025,8,29]]},"article-number":"bgaf052"}}