{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T02:19:10Z","timestamp":1780366750299,"version":"3.54.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Pancreatic cancer is a highly lethal cancer with increasing incidence and poor prognosis due to late diagnosis. While several risk factors are known, evidence on a potential role of autoimmune diseases remains limited. Given the increasing prevalence of autoimmune diseases and their association with various malignancies, this study aims to investigate their potential association with pancreatic cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>5,440 patients with a first diagnosis of pancreatic cancer and 27,200 propensity score matched individuals without cancer were identified from the Disease Analyzer database (IQVIA). The outcome of the study was the association between the diagnosis of pancreatic cancer and a patient\u00b4s history of autoimmune disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Inflammatory bowel disease (OR: 1.69; 95% CI: 1.34-2.12) and rheumatoid arthritis (OR: 1.20; 95% CI: 1.03-1.41) were significantly associated with increased odds of pancreatic cancer. The OR was 1.25 for systemic lupus erythematosus and 1.26 for multiple sclerosis without reaching a statistical significance. In sex-stratified analyses, inflammatory bowel disease was strongly associated with pancreatic cancer in women (OR: 2.14; 95% CI: 1.59-2.89) but not in men (OR: 1.24; 95% CI: 0.86-1.78). A positive association between rheumatoid arthritis and pancreatic cancer was also observed in women (OR: 1.26; 95% CI: 1.03-1.53) but not in men (OR: 1.09; 95% CI: 1.03-1.53-1.44). In addition, the ORs for SLE (1.82) and MS (1.45) were increased in women to a clinically relevant extent that did not reach the significance level of &amp;lt;0.05. A similar increase was not observed in male patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Autoimmune disease may be associated with an increased risk of developing pancreatic cancer, particularly in women. This highlights the importance of addressing gender differences in medical practice, particularly in relation to disease screening and surveillance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1613787","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:11:53Z","timestamp":1751965913000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["A sex dependent association between the history of autoimmune disease and the development of pancreatic cancer: a case-control study of 32,640 patients"],"prefix":"10.3389","volume":"15","author":[{"given":"Sven H.","family":"Loosen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederik J.","family":"Hansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Luedde","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Roderburg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"Kostev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2022.04.047","article-title":"A path forward for understanding and addressing multifaceted pancreatic cancer disparities","volume":"163","author":"Permuth","year":"2022","journal-title":"Gastroenterology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v28.i32.4698","article-title":"International patterns in incidence and mortality trends of pancreatic cancer in the last three decades: A joinpoint regression analysis","volume":"28","author":"Ilic","year":"2022","journal-title":"World J Gastroenterol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1016\/S2468-1253(23)00039-0","article-title":"Cause for concern: the rising incidence of early-onset pancreatic cancer","volume":"8","year":"2023","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"141","DOI":"10.1186\/s13014-019-1345-6","article-title":"Pancreatic ductal adenocarcinoma: biological hallmarks, current status, and future perspectives of combined modality treatment approaches","volume":"14","author":"Orth","year":"2019","journal-title":"Radiat Oncol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1038\/s41571-023-00746-1","article-title":"Neoadjuvant therapy for pancreatic cancer","volume":"20","author":"Springfeld","year":"2023","journal-title":"Nat Rev Clin Oncol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-018-0005-x","article-title":"Therapeutic developments in pancreatic cancer: current and future perspectives","volume":"15","author":"Neoptolemos","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1053\/j.gastro.2022.03.056","article-title":"Pancreatic cancer: pathogenesis, screening, diagnosis, and treatment","volume":"163","author":"Wood","year":"2022","journal-title":"Gastroenterology"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-021-00475-9","article-title":"Scaling the immune incline in PDAC","volume":"18","author":"Rojas","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B9","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1038\/s41575-021-00476-8","article-title":"Improved CAR T therapy for PDAC","volume":"18","author":"Dickson","year":"2021","journal-title":"Nat Rev Gastroenterol Hepatol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.13027","article-title":"Pancreatic cancer: A review","volume":"326","author":"Park","year":"2021","journal-title":"JAMA"},{"key":"B11","doi-asserted-by":"publisher","first-page":"4138","DOI":"10.3390\/cancers13164138","article-title":"Pancreatic cancer and immunotherapy: A clinical overview","volume":"13","author":"Timmer","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6712a1","article-title":"Surveillance for cancers associated with tobacco use - United States, 2010-2014","volume":"67","author":"Gallaway","year":"2018","journal-title":"MMWR Surveill Summ"},{"key":"B13","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1056\/NEJMoa1614362","article-title":"Health effects of overweight and obesity in 195 countries over 25 years","volume":"377","author":"Afshin","year":"2017","journal-title":"N Engl J Med"},{"key":"B14","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1002\/mc.20771","article-title":"Diabetes and pancreatic cancer","volume":"51","author":"Li","year":"2012","journal-title":"Mol Carcinog"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1136\/gut.51.6.849","article-title":"Risk of pancreatic adenocarcinoma in chronic pancreatitis","volume":"51","author":"Malka","year":"2002","journal-title":"Gut"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/ijc.31367","article-title":"Lifetime and baseline alcohol intakes and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition study","volume":"143","author":"Naudin","year":"2018","journal-title":"Int J Cancer"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(23)00457-9","article-title":"Incidence, prevalence, and co-occurrence of autoimmune disorders over time and by age, sex, and socioeconomic status: a population-based cohort study of 22 million individuals in the UK","volume":"401","author":"Conrad","year":"2023","journal-title":"Lancet"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.gtc.2022.05.003","article-title":"Cancer in inflammatory bowel disease","volume":"51","author":"Faye","year":"2022","journal-title":"Gastroenterol Clin North Am"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyae006","article-title":"Rheumatoid arthritis and cancer risk in the Million Women Study","volume":"53","author":"Yang","year":"2024","journal-title":"Int J Epidemiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1097\/RHU.0000000000001729","article-title":"The cancer risk profile of systemic lupus erythematosus patients","volume":"28","author":"Hardenbergh","year":"2022","journal-title":"J Clin Rheumatol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0298271","article-title":"Association between multiple sclerosis and cancer risk: A two-sample Mendelian randomization study","volume":"19","author":"Liu","year":"2024","journal-title":"PloS One"},{"key":"B22","doi-asserted-by":"publisher","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":"B23","doi-asserted-by":"publisher","first-page":"53","DOI":"10.1007\/s00432-023-05534-z","article-title":"Association between iron deficiency anemia and subsequent stomach and colorectal cancer diagnosis in Germany","volume":"150","author":"Krieg","year":"2024","journal-title":"J Cancer Res Clin Oncol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"5584","DOI":"10.3390\/jcm13185584","article-title":"Elevated hbA1c levels are associated with a risk of pancreatic cancer: A case-control study","volume":"13","author":"Grewe","year":"2024","journal-title":"J Clin Med"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1533033820962117","DOI":"10.1177\/1533033820962117","article-title":"Pancreatic cancer: A review of risk factors, diagnosis, and treatment","volume":"19","author":"Zhao","year":"2020","journal-title":"Technol Cancer Res Treat"},{"key":"B26","doi-asserted-by":"publisher","first-page":"676","DOI":"10.3390\/ijms20030676","article-title":"Inflammation and pancreatic cancer: focus on metabolism, cytokines, and immunity","volume":"20","author":"Padoan","year":"2019","journal-title":"Int J Mol Sci"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0896","article-title":"IL17 functions through the novel REG3beta-JAK2-STAT3 inflammatory pathway to promote the transition from chronic pancreatitis to pancreatic cancer","volume":"75","author":"Loncle","year":"2015","journal-title":"Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.4161\/gmic.19625","article-title":"Involvement of gut microbiota in the development of low-grade inflammation and type 2 diabetes associated with obesity","volume":"3","author":"Cani","year":"2012","journal-title":"Gut Microbes"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2019.1629235","article-title":"Lipopolysaccharides modulate intestinal epithelial permeability and inflammation in a species-specific manner","volume":"11","author":"Stephens","year":"2020","journal-title":"Gut Microbes"},{"key":"B30","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1038\/s41420-022-00849-1","article-title":"METTL3 overexpression aggravates LPS-induced cellular inflammation in mouse intestinal epithelial cells and DSS-induced IBD in mice","volume":"8","author":"Yang","year":"2022","journal-title":"Cell Death Discov"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1097\/MIB.0000000000000236","article-title":"Cytokines, IBD, and colitis-associated cancer","volume":"21","author":"Francescone","year":"2015","journal-title":"Inflammation Bowel Dis"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1038\/s41590-020-00816-x","article-title":"The immunology of rheumatoid arthritis","volume":"22","author":"Weyand","year":"2021","journal-title":"Nat Immunol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"10922","DOI":"10.3390\/ijms222010922","article-title":"Cytokine networks in the pathogenesis of rheumatoid arthritis","volume":"22","author":"Kondo","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2024.46336","article-title":"Use of biologic or targeted synthetic disease-Modifying antirheumatic drugs and cancer risk","volume":"7","author":"Sendaydiego","year":"2024","journal-title":"JAMA Netw Open"},{"key":"B35","doi-asserted-by":"publisher","first-page":"270","DOI":"10.1186\/s13075-018-1760-3","article-title":"The risks of cancer development in systemic lupus erythematosus (SLE) patients: a systematic review and meta-analysis","volume":"20","author":"Song","year":"2018","journal-title":"Arthritis Res Ther"},{"key":"B36","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1007\/s11926-021-00984-1","article-title":"A review of complement activation in SLE","volume":"23","author":"Weinstein","year":"2021","journal-title":"Curr Rheumatol Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"102736","DOI":"10.1016\/j.autrev.2020.102736","article-title":"B cell activating factor (BAFF): Structure, functions, autoimmunity and clinical implications in Systemic Lupus Erythematosus (SLE)","volume":"20","author":"Mockel","year":"2021","journal-title":"Autoimmun Rev"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.867902","article-title":"B-lymphocytes in the pathophysiology of pancreatic adenocarcinoma","volume":"13","author":"Minici","year":"2022","journal-title":"Front Immunol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"105098","DOI":"10.1016\/j.ebiom.2024.105098","article-title":"Intratumoral CD38(+)CD19(+)B cells associate with poor clinical outcomes and immunosuppression in patients with pancreatic ductal adenocarcinoma","volume":"103","author":"Zhu","year":"2024","journal-title":"EBioMedicine"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellimm.2015.01.018","article-title":"Estrogen receptors regulate innate immune cells and signaling pathways","volume":"294","author":"Kovats","year":"2015","journal-title":"Cell Immunol"},{"key":"B41","doi-asserted-by":"publisher","first-page":"97","DOI":"10.2174\/1568010043483944","article-title":"Estrogen, a double-edged sword: modulation of TH1- and TH2-mediated inflammations by differential regulation of TH1\/TH2 cytokine production","volume":"3","author":"Salem","year":"2004","journal-title":"Curr Drug Targets Inflammation Allergy"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1111\/j.1398-9995.2009.02291.x","article-title":"X-chromosome Forkhead Box P3 polymorphisms associate with atopy in girls in three Dutch birth cohorts","volume":"65","author":"Bottema","year":"2010","journal-title":"Allergy"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adn6537","article-title":"Altered X-chromosome inactivation predisposes to autoimmunity","volume":"10","author":"Huret","year":"2024","journal-title":"Sci Adv"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34479","article-title":"Annual report to the nation on the status of cancer, part 1: National cancer statistics","volume":"128","author":"Cronin","year":"2022","journal-title":"Cancer"},{"key":"B45","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1136\/gutjnl-2019-319352","article-title":"Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium","volume":"69","author":"Goggins","year":"2020","journal-title":"Gut"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1613787\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T09:11:53Z","timestamp":1751965913000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1613787\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,8]]},"references-count":45,"alternative-id":["10.3389\/fonc.2025.1613787"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1613787","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,8]]},"article-number":"1613787"}}