{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T05:26:28Z","timestamp":1779341188451,"version":"3.51.4"},"reference-count":22,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,8]],"date-time":"2022-11-08T00:00:00Z","timestamp":1667865600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["110043"],"award-info":[{"award-number":["110043"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["TRR57\/P06"],"award-info":[{"award-number":["TRR57\/P06"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["LU 1360\/3-1"],"award-info":[{"award-number":["LU 1360\/3-1"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["CRC1380\/A01"],"award-info":[{"award-number":["CRC1380\/A01"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council","doi-asserted-by":"publisher","award":["CA 830\/3-1"],"award-info":[{"award-number":["CA 830\/3-1"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["110043"],"award-info":[{"award-number":["110043"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["TRR57\/P06"],"award-info":[{"award-number":["TRR57\/P06"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["LU 1360\/3-1"],"award-info":[{"award-number":["LU 1360\/3-1"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["CRC1380\/A01"],"award-info":[{"award-number":["CRC1380\/A01"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000781","name":"European Research Council (ERC)","doi-asserted-by":"publisher","award":["CA 830\/3-1"],"award-info":[{"award-number":["CA 830\/3-1"]}],"id":[{"id":"10.13039\/501100000781","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["771083"],"award-info":[{"award-number":["771083"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["110043"],"award-info":[{"award-number":["110043"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["TRR57\/P06"],"award-info":[{"award-number":["TRR57\/P06"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["LU 1360\/3-1"],"award-info":[{"award-number":["LU 1360\/3-1"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["CRC1380\/A01"],"award-info":[{"award-number":["CRC1380\/A01"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005972","name":"German Cancer Aid","doi-asserted-by":"publisher","award":["CA 830\/3-1"],"award-info":[{"award-number":["CA 830\/3-1"]}],"id":[{"id":"10.13039\/501100005972","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German-Research-Foundation","award":["771083"],"award-info":[{"award-number":["771083"]}]},{"name":"German-Research-Foundation","award":["771083"],"award-info":[{"award-number":["771083"]}]},{"name":"German-Research-Foundation","award":["110043"],"award-info":[{"award-number":["110043"]}]},{"name":"German-Research-Foundation","award":["TRR57\/P06"],"award-info":[{"award-number":["TRR57\/P06"]}]},{"name":"German-Research-Foundation","award":["LU 1360\/3-1"],"award-info":[{"award-number":["LU 1360\/3-1"]}]},{"name":"German-Research-Foundation","award":["CRC1380\/A01"],"award-info":[{"award-number":["CRC1380\/A01"]}]},{"name":"German-Research-Foundation","award":["CA 830\/3-1"],"award-info":[{"award-number":["CA 830\/3-1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Antihypertensive pharmacological therapy includes diuretics, beta-blockers, ACE inhibitors, calcium channel blockers and angiotensin II receptor blockers. Besides their use in arterial hypertension, these drugs also play a major role in the therapy of portal hypertension, heart failure and coronary artery disease. Systematic analyses on the possible influence of these medications on cancer incidence are lacking. Methods: By utilizing the Disease Analyzer database (IQVIA), 349,210 patients with antihypertensive drug prescriptions between 2010 and 2020 without a diagnosis of cancer prior to or at the date of initial drug prescription were included. Propensity score matching was carried out by 1:1:1:1:1 according to the five antihypertensive treatments. Cox regression analyses were performed to investigate an association between antihypertensive drugs and the incidence of cancer. Results: Patients who were diagnosed with cancer were treated with diuretics in 19.9% of cases, calcium channel blockers in 16.9% of cases, and angiotensin II receptor blockers, ACE inhibitors, or beta-blockers in 13.9%, 13.2% and 12.8% of cases, respectively. Cox regression models revealed that diuretic use positively correlated with liver cancer incidence (HR: 1.31, 95%CI: 1.12\u20132.63) and lymphoid\/haematopoietic tissue cancer incidence (HR: 1.27, 95%CI: 1.10\u20131.46). Use of diuretics negatively correlated with the incidence of prostate (HR: 0.64, 95%CI: 0.53\u20130.78) and skin cancer (HR: 0.81, 95%CI: 0.72\u20130.92). Finally, a positive association was found between angiotensin II receptor inhibitors and prostate cancer incidence (HR: 1.50, 95%CI: 1.28\u20131.65). Conclusions: These data suggest that diuretic use might be associated with liver cancer and lymphoid\/haematopoetic tissue cancer development.<\/jats:p>","DOI":"10.3390\/jcm11226624","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T02:44:32Z","timestamp":1667961872000},"page":"6624","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Antihypertensive Therapy and Incidence of Cancer"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2799-2287","authenticated-orcid":false,"given":"Sven H.","family":"Loosen","sequence":"first","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty of Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2736-9778","authenticated-orcid":false,"given":"David","family":"Sch\u00f6ler","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty of Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8149-8087","authenticated-orcid":false,"given":"Mark","family":"Luedde","sequence":"additional","affiliation":[{"name":"KGP Bremerhaven, 27574 Bremerhaven, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7390-6431","authenticated-orcid":false,"given":"Johannes","family":"Eschrich","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology, Charit\u00e9 University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty of Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9015-3646","authenticated-orcid":false,"given":"Niklas","family":"Gremke","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Philipps-University, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Kalder","sequence":"additional","affiliation":[{"name":"Department of Gynecology and Obstetrics, Philipps-University, 35043 Marburg, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2124-7227","authenticated-orcid":false,"given":"Karel","family":"Kostev","sequence":"additional","affiliation":[{"name":"Epidemiology, IQVIA, 60549 Frankfurt, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Roderburg","sequence":"additional","affiliation":[{"name":"Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital D\u00fcsseldorf, Medical Faculty of Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/S0140-6736(21)01330-1","article-title":"Worldwide trends in hypertension prevalence and progress in treatment and control from 1990 to 2019: A pooled analysis of 1201 population-representative studies with 104 million participants","volume":"398","author":"Zhou","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1146\/annurev.publhealth.27.021405.102132","article-title":"Hypertension: Trends in prevalence, incidence, and control","volume":"27","author":"Hajjar","year":"2006","journal-title":"Annu. Rev. Public Health"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1177\/2047487319884823","article-title":"Antihypertensive drugs and the risks of cancer: More fakes than facts","volume":"28","author":"Battistoni","year":"2021","journal-title":"Eur. J. Prev. Cardiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1097\/HCO.0b013e328353bc4f","article-title":"Which, if any, antihypertensive agents cause cancer?","volume":"27","author":"Singh","year":"2012","journal-title":"Curr. Opin. Cardiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/S1470-2045(21)00033-4","article-title":"Antihypertensive treatment and risk of cancer: An individual participant data meta-analysis","volume":"22","author":"Copland","year":"2021","journal-title":"Lancet Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"459","DOI":"10.5414\/CP203320","article-title":"Basic characteristics and representativeness of the German Disease Analyzer database","volume":"56","author":"Rathmann","year":"2018","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"162","DOI":"10.5414\/CP203088","article-title":"Persistence with antihypertensive drugs in patients with depression in Germany","volume":"56","author":"Jacob","year":"2018","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"483","DOI":"10.5414\/CP203559","article-title":"The association between antihypertensive therapy and the incidence of Parkinson\u2019s disease in patients followed in general practices in Germany","volume":"57","author":"Warda","year":"2019","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Loosen, S.H., J\u00f6rdens, M.S., Luedde, M., Modest, D.P., Labuhn, S., Luedde, T., Kostev, K., and Roderburg, C. (2021). Incidence of Cancer in Patients with Irritable Bowl Syndrome. J. Clin. Med., 10.","DOI":"10.3390\/jcm10245911"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Loosen, S.H., Roderburg, C., J\u00f6rdens, M.S., Fluegen, G., Luedde, T., and Kostev, K. (2022). Overweight and Obesity Determine the Risk for Gastrointestinal Cancer in a Sex-Dependent Manner: A Retrospective Cohort Study of 287,357 Outpatients in Germany. Cancers, 14.","DOI":"10.3390\/cancers14040931"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1002\/hep.31157","article-title":"Risk of Cirrhosis and Hepatocellular Cancer in Patients With NAFLD and Normal Liver Enzymes","volume":"72","author":"Natarajan","year":"2020","journal-title":"Hepatology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/sj.jhh.1002075","article-title":"Hypertension, diuretics and breast cancer risk","volume":"20","author":"Largent","year":"2006","journal-title":"J. Hum. Hypertens."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.repc.2019.07.008","article-title":"Hydrochlorothiazide treatment and risk of non-melanoma skin cancer: Review of the literature","volume":"39","author":"Garrido","year":"2020","journal-title":"Rev. Port. Cardiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12292","DOI":"10.1038\/srep12292","article-title":"Hyperosmotic stress activates the expression of members of the miR-15\/107 family and induces downregulation of anti-apoptotic genes in rat liver","volume":"5","author":"Santosa","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100440","DOI":"10.1016\/j.jhepr.2022.100440","article-title":"Swelling-induced upregulation of miR-141-3p inhibits hepatocyte proliferation","volume":"4","author":"Bardeck","year":"2022","journal-title":"JHEP Rep."},{"key":"ref_16","first-page":"F756","article-title":"Thiazide induces water absorption in the inner medullary collecting duct of normal and Brattleboro rats","volume":"277","author":"Magaldi","year":"1999","journal-title":"Am. J. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1111\/bcp.13152","article-title":"Spironolactone use and risk of incident cancers: A retrospective, matched cohort study","volume":"83","author":"Mackenzie","year":"2017","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1111\/bcp.14568","article-title":"Impact of spironolactone exposure on prostate cancer incidence amongst men with heart failure: A Pharmacoepidemiological study","volume":"87","author":"Hiebert","year":"2021","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Cao, L., Zhang, S., Jia, C.M., He, W., Wu, L.T., Li, Y.Q., Wang, W., Li, Z., and Ma, J. (2018). Antihypertensive drugs use and the risk of prostate cancer: A meta-analysis of 21 observational studies. BMC Urol., 18.","DOI":"10.1186\/s12894-018-0318-7"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1158\/1535-7163.MCT-04-0295","article-title":"Antiproliferative activity of angiotensin II receptor blocker through cross-talk between stromal and epithelial prostate cancer cells","volume":"4","author":"Uemura","year":"2005","journal-title":"Mol. Cancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1002\/jcph.98","article-title":"Angiotensin receptor blockers and risk of prostate cancer among united states veterans","volume":"53","author":"Rao","year":"2013","journal-title":"J. Clin. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s11906-014-0461-9","article-title":"Genetics, ancestry, and hypertension: Implications for targeted antihypertensive therapies","volume":"16","author":"Franceschini","year":"2014","journal-title":"Curr. Hypertens. Rep."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/22\/6624\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:12:47Z","timestamp":1760145167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/22\/6624"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,11,8]]},"references-count":22,"journal-issue":{"issue":"22","published-online":{"date-parts":[[2022,11]]}},"alternative-id":["jcm11226624"],"URL":"https:\/\/doi.org\/10.3390\/jcm11226624","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,11,8]]}}}