{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:06:34Z","timestamp":1791353194190,"version":"4.3.1"},"reference-count":26,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T00:00:00Z","timestamp":1620345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Tri-Service General Hospital Research Foundation","award":["TSGH-B-110012"],"award-info":[{"award-number":["TSGH-B-110012"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>Tuberculosis (TB) presents a global threat in the world and the lung is the frequent site of metastatic focus. A previous study demonstrated that TB might increase primary lung cancer risk by two-fold for more than 20 years after the TB diagnosis. However, no large-scale study has evaluated the risk of TB and secondary lung cancer. Thus, we evaluated the risk of secondary lung cancer in patients with or without tuberculosis (TB) using a nationwide population-based dataset.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>In a cohort study of 1,936,512 individuals, we selected 6934 patients among patients with primary cancer and TB infection, based on the International Classification of Disease (ICD-p-CM) codes 010\u2013011 from 2000 to 2015. The control cohort comprised 13,868 randomly selected, propensity-matched patients (by age, gender, and index date) without TB exposure. Using this adjusted date, a possible association between TB and the risk of developing secondary lung cancer was estimated using a Cox proportional hazards regression model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>During the follow-up period, secondary lung cancer was diagnosed in 761 (10.97%) patients with TB and 1263 (9.11%) patients without TB. After adjusting for covariates, the risk of secondary lung cancer was 1.67 times greater among primary cancer in the cohort with TB than in the cohort without TB. Stratification revealed that every comorbidity (including diabetes, hypertension, cirrhosis, congestive heart failure, cardiovascular accident, chronic kidney disease, chronic obstructive pulmonary disease) significantly increased the risk of secondary lung cancer when comparing the TB cohort with the non-TB cohort. Moreover, the primary cancer types (including head and neck, colorectal cancer, soft tissue sarcoma, breast, kidney, and thyroid cancer) had a more significant risk of becoming secondary lung cancer.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>A significant association exists between TB and the subsequent risk for metastasis among primary cancers and comorbidities. Therefore, TB patients should be evaluated for the subsequent risk of secondary lung cancer.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0250531","type":"journal-article","created":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T18:33:24Z","timestamp":1620412404000},"page":"e0250531","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":46,"title":["Increased risk of secondary lung cancer in patients with tuberculosis: A nationwide, population-based cohort study"],"prefix":"10.1371","volume":"16","author":[{"given":"Li-Ju","family":"Ho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Yi","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Hsiang","family":"Chung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chin","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sung-Sen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-An","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3286-0780","authenticated-orcid":true,"given":"Wu-Chien","family":"Chien","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6728-8705","authenticated-orcid":true,"given":"Ruei-Yu","family":"Su","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2021,5,7]]},"reference":[{"key":"pone.0250531.ref001","unstructured":"World Health Organization 2020. Available from: https:\/\/www.who.int\/health-topics\/tuberculosis-tab=tab_1."},{"issue":"7","key":"pone.0250531.ref002","doi-asserted-by":"crossref","DOI":"10.3390\/cancers11071010","article-title":"Lung-Seeking Metastases.","volume":"11","author":"GM Stella","year":"2019","journal-title":"Cancers (Basel)."},{"issue":"28","key":"pone.0250531.ref003","doi-asserted-by":"crossref","first-page":"46491","DOI":"10.18632\/oncotarget.14822","article-title":"Clinical characteristics and prognoses of patients treated surgically for metastatic lung tumors","volume":"8","author":"X Zhao","year":"2017","journal-title":"Oncotarget"},{"issue":"12","key":"pone.0250531.ref004","doi-asserted-by":"crossref","first-page":"2936","DOI":"10.1002\/ijc.24636","article-title":"Facts and fiction of the relationship between preexisting tuberculosis and lung cancer risk: a systematic review","volume":"125","author":"HY Liang","year":"2009","journal-title":"Int J Cancer"},{"issue":"1","key":"pone.0250531.ref005","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1093\/ije\/30.1.118","article-title":"Previous pulmonary diseases and risk of lung cancer in Gansu Province, China","volume":"30","author":"AV Brenner","year":"2001","journal-title":"Int J Epidemiol"},{"issue":"4","key":"pone.0250531.ref006","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1158\/1055-9965.EPI-10-1166","article-title":"Increased risk of lung cancer in men with tuberculosis in the alpha-tocopherol, beta-carotene cancer prevention study","volume":"20","author":"MS Shiels","year":"2011","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"issue":"3","key":"pone.0250531.ref007","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1002\/cncr.25616","article-title":"Pulmonary tuberculosis increases the risk of lung cancer: a population-based cohort study","volume":"117","author":"CY Wu","year":"2011","journal-title":"Cancer"},{"issue":"1","key":"pone.0250531.ref008","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1097\/JTO.0b013e3181fb4fcc","article-title":"Increased lung cancer risk among patients with pulmonary tuberculosis: a population cohort study","volume":"6","author":"YH Yu","year":"2011","journal-title":"J Thorac Oncol"},{"issue":"7","key":"pone.0250531.ref009","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1093\/aje\/kws151","article-title":"Previous lung diseases and lung cancer risk: a pooled analysis from the International Lung Cancer Consortium","volume":"176","author":"DR Brenner","year":"2012","journal-title":"Am J Epidemiol"},{"issue":"6","key":"pone.0250531.ref010","doi-asserted-by":"crossref","first-page":"757","DOI":"10.5588\/ijtld.15.0783","article-title":"Incidence of lung cancer among patients with tuberculosis: a nationwide cohort study in Lithuania.","volume":"20","author":"R Everatt","year":"2016","journal-title":"Int J Tuberc Lung Dis"},{"issue":"11","key":"pone.0250531.ref011","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1002\/ijc.30384","article-title":"Tuberculosis, smoking and risk for lung cancer incidence and mortality","volume":"139","author":"S Hong","year":"2016","journal-title":"Int J Cancer"},{"issue":"Pt 2","key":"pone.0250531.ref012","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1177\/000456329703400205","article-title":"Elevated concentrations of interleukins and leukotriene in response to Mycobacterium tuberculosis infection","volume":"34","author":"O el-Ahmady","year":"1997","journal-title":"Ann Clin Biochem"},{"issue":"2","key":"pone.0250531.ref013","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1046\/j.1365-2567.2002.01403.x","article-title":"The role of prostaglandin E2 in the immunopathogenesis of experimental pulmonary tuberculosis","volume":"106","author":"J Rangel Moreno","year":"2002","journal-title":"Immunology"},{"issue":"7","key":"pone.0250531.ref014","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/qjmed\/hcq068","article-title":"Tuberculosis and malignancy","volume":"103","author":"ME Falagas","year":"2010","journal-title":"Qjm"},{"issue":"4","key":"pone.0250531.ref015","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1515\/BC.2006.049","article-title":"Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis","volume":"387","author":"S Kawanishi","year":"2006","journal-title":"Biol Chem"},{"issue":"9","key":"pone.0250531.ref016","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1111\/j.1348-0421.2005.tb03673.x","article-title":"Survival of virulent Mycobacterium tuberculosis involves preventing apoptosis induced by Bcl-2 upregulation and release resulting from necrosis in J774 macrophages","volume":"49","author":"J Zhang","year":"2005","journal-title":"Microbiol Immunol"},{"issue":"3","key":"pone.0250531.ref017","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1177\/1534735403256332","article-title":"Inflammation as cause for scar cancers of the lung","volume":"2","author":"CM Ardies","year":"2003","journal-title":"Integr Cancer Ther"},{"issue":"6","key":"pone.0250531.ref018","doi-asserted-by":"crossref","first-page":"716","DOI":"10.1001\/jama.294.6.716","article-title":"Clinical practice guidelines and quality of care for older patients with multiple comorbid diseases: implications for pay for performance","volume":"294","author":"CM Boyd","year":"2005","journal-title":"Jama"},{"issue":"5","key":"pone.0250531.ref019","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1002\/sim.4454","article-title":"Predicting the absolute risk of dying from colorectal cancer and from other causes using population-based cancer registry data","volume":"31","author":"M Lee","year":"2012","journal-title":"Stat Med"},{"issue":"3","key":"pone.0250531.ref020","doi-asserted-by":"crossref","first-page":"110","DOI":"10.2188\/jea.JE20170241","article-title":"Impact of Comorbidities on Survival in Gastric, Colorectal, and Lung Cancer Patients","volume":"29","author":"T Morishima","year":"2019","journal-title":"J Epidemiol"},{"issue":"4","key":"pone.0250531.ref021","doi-asserted-by":"crossref","first-page":"928","DOI":"10.1183\/09031936.00214014","article-title":"Towards tuberculosis elimination: an action framework for low-incidence countries","volume":"45","author":"K L\u00f6nnroth","year":"2015","journal-title":"Eur Respir J"},{"issue":"4","key":"pone.0250531.ref022","doi-asserted-by":"crossref","first-page":"654","DOI":"10.2105\/AJPH.2010.199505","article-title":"The social determinants of tuberculosis: from evidence to action","volume":"101","author":"JR Hargreaves","year":"2011","journal-title":"Am J Public Health"},{"issue":"9728","key":"pone.0250531.ref023","doi-asserted-by":"crossref","first-page":"1814","DOI":"10.1016\/S0140-6736(10)60483-7","article-title":"Tuberculosis control and elimination 2010\u201350: cure, care, and social development","volume":"375","author":"K L\u00f6nnroth","year":"2010","journal-title":"Lancet"},{"issue":"12","key":"pone.0250531.ref024","doi-asserted-by":"crossref","first-page":"2240","DOI":"10.1016\/j.socscimed.2009.03.041","article-title":"Drivers of tuberculosis epidemics: the role of risk factors and social determinants","volume":"68","author":"K L\u00f6nnroth","year":"2009","journal-title":"Soc Sci Med"},{"issue":"2","key":"pone.0250531.ref025","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1080\/17571472.2010.11493315","article-title":"An overview of the healthcare system in Taiwan.","volume":"3","author":"TY Wu","year":"2010","journal-title":"London J Prim Care (Abingdon)."},{"issue":"3","key":"pone.0250531.ref026","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1200\/JGO.2015.002089","article-title":"Pulmonary Nodules in Patients With Nonpulmonary Cancer: Not Always Metastases.","volume":"2","author":"R Caparica","year":"2016","journal-title":"J Glob Oncol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250531","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,5,7]],"date-time":"2021-05-07T18:34:15Z","timestamp":1620412455000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0250531"}},"subtitle":[],"editor":[{"given":"Suresh kumar","family":"Subbiah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2021,5,7]]},"references-count":26,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,5,7]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0250531","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,7]]}}}