{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:48:07Z","timestamp":1782114487410,"version":"3.54.5"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer\u2010related mortality worldwide. Preclinical studies suggest that the renin\u2013angiotensin\u2013aldosterone system (RAAS) inhibitors may help prevent PDAC by promoting acinar ductal metaplasia reversal, as the RAAS pathway is most inhibited during this process. Our study aims to examine the association between RAAS inhibitor use and the risk of PDAC compared with calcium channel blockers (CCB). Leveraging the target trial emulation framework, we used US Medicare data to emulate a new user, active comparator trial examining the effects of initiating RAAS inhibitors (exposure group) versus CCB (control group), with randomization emulated by propensity score matching with 2:1 ratio. Eligible patients were aged &gt;65\u2009years without malignant cancer or palliative care. Outcomes included PDAC and all\u2010cause mortality. Cox proportional hazards models with inverse probability censoring weight were applied. After propensity score matching, our study included 214,262 patients who initiated RAAS inhibitors and 107,131 patients who initiated CCB, with mean ages of 76.5 and 77.0\u2009years, respectively, and a similar proportion of women (60.9% vs. 61.8%) between two groups. During follow\u2010up, the incidence of PDAC was significantly lower in the RAAS inhibitor group than in the CCB group, corresponding to a 46% reduction in PDAC risk (hazard ratio [HR]: 0.54, 95% confidence interval [CI]: 0.49\u20130.59). Similarly, all\u2010cause mortality was 22% lower among RAAS inhibitors users compared with CCB users (HR: 0.78, 95% CI: 0.77\u20130.79). These findings warrant further investigation into RAAS inhibitors' potential benefits, including identification of confounding factors like genetics and biomarkers.<\/jats:p>","DOI":"10.1002\/ijc.70438","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T04:26:42Z","timestamp":1774326402000},"page":"853-863","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Renin\u2013angiotensin\u2013aldosterone system inhibitors and risk of pancreatic cancer in older adults: A target trial emulation"],"prefix":"10.1002","volume":"159","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-0487-9171","authenticated-orcid":false,"given":"Fanxing","family":"Du","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy College of Pharmacy, University of Florida  Gainesville Florida USA"},{"name":"Center for Drug Evaluation and Safety University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"George","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Medicine College of Medicine, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0587-4105","authenticated-orcid":false,"given":"Yi","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Health Outcomes and Biomedical Informatics College of Medicine, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzin","family":"Khosrow\u2010Khavar","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Epidemiology School of Public Health, Rutgers, The State University of New Jersey  New Brunswick New Jersey USA"},{"name":"Center for Pharmacoepidemiology and Treatment Science, Institute for Health, Rutgers, The State University of New Jersey  New Brunswick New Jersey USA"},{"name":"Rutgers Cancer Institute  New Brunswick New Jersey USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy College of Pharmacy, University of Florida  Gainesville Florida USA"},{"name":"Center for Drug Evaluation and Safety University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corey M.","family":"Perkins","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinmai","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"DeRemer","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caitrin","family":"McDonough","sequence":"additional","affiliation":[{"name":"Department of Pharmacotherapy and Translational Research College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Epidemiology and Informatics Perelman School of Medicine, University of Pennsylvania  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas D.","family":"Schmittgen","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianze","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Outcomes and Policy College of Pharmacy, University of Florida  Gainesville Florida USA"},{"name":"Center for Drug Evaluation and Safety University of Florida  Gainesville Florida USA"},{"name":"Cardio\u2010Oncology Working Group University of Florida Health Cancer Institute  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010025\u201013471\u2010y"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21763"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008\u20105472.Can\u201014\u20100155"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1011923"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1304369"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(23)01366\u20101"},{"key":"e_1_2_11_8_1","unstructured":"FDA.FDA approves pembrolizumab for adults and children with TMB\u2010H solid tumors.https:\/\/www.fda.gov\/drugs\/drug-approvals-and-databases\/fda-approves-pembrolizumab-adults-and-children-tmb-h-solid-tumors"},{"key":"e_1_2_11_9_1","unstructured":"Merck.FDA converts to full approval indication for KEYTRUDA\u00ae (pembrolizumab) for certain adult and pediatric patients with advanced microsatellite instability\u2010high (MSI\u2010H) or mismatch repair deficient (dMMR) solid tumors.2023https:\/\/www.merck.com\/news\/fda\u2010converts\u2010to\u2010full\u2010approval\u2010indication\u2010for\u2010keytruda\u2010pembrolizumab\u2010for\u2010certain\u2010adult\u2010and\u2010pediatric\u2010patients\u2010with\u2010advanced\u2010microsatellite\u2010instability\u2010high\u2010msi\u2010h\u2010or\u2010mismatch\u2010repair\u2010deficient\/"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11864\u2010018\u20100566\u20105"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2208470"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2007.01.012"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2021.11.010"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24129946"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmgh.2017.05.005"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.07125"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI40045"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420\u2010022\u201001165\u20104"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1335246"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gastha.2023.02.003"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0221810"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.0.0260155"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1357\u20102725(02)00179\u20106"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.regpep.2004.02.003"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201022\u20101630"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2019.0892"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000019075"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1093\/pubmed\/fdt116"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.2147\/CLEP.S91125"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.375"},{"key":"e_1_2_11_31_1","volume-title":"The Clinical Management of Primary Hypertension in Adults","author":"NICE","year":"2011"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.21383"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.113.000125"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijo.2016.3512"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1470\u20102045(21)00033\u20104"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm10040771"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.122.026789"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwad091"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e31825f3af4"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2003.50147"},{"key":"e_1_2_11_41_1","unstructured":"National Cancer Institute.Cancer stat facts: pancreatic cancer.https:\/\/seer.cancer.gov\/statfacts\/html\/pancreas.html"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/jaha.116.004758"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2019.05.059"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.119.013754"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cpcardiol.2024.102389"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2021.09.008"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/pds.1869"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/hpae093"}],"container-title":["International Journal of Cancer"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70438","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ijc.70438","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ijc.70438","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T07:07:38Z","timestamp":1782112058000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ijc.70438"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,23]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,8,15]]}},"alternative-id":["10.1002\/ijc.70438"],"URL":"https:\/\/doi.org\/10.1002\/ijc.70438","archive":["Portico"],"relation":{},"ISSN":["0020-7136","1097-0215"],"issn-type":[{"value":"0020-7136","type":"print"},{"value":"1097-0215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,23]]},"assertion":[{"value":"2025-09-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-02-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}