{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T22:12:19Z","timestamp":1767046339581,"version":"build-2065373602"},"reference-count":44,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T00:00:00Z","timestamp":1691366400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Previous studies demonstrated unclear and vast variability in the association between Ankylosing Spondylitis (AS) and the risk of cancer. Objectives: To assess the risk of overall and site-specific malignancies for AS patients in Israel, while examining the role of comorbidities and immunomodulatory therapy. Methods: We conducted a retrospective electronic data-based study including all AS patients diagnosed between 2002 and 2018, with no history of cancer prior to enrollment, with 5:1 ratio matched-control by age, gender, and place of residence. The odds Ratios (OR) for site-specific malignancies, comparing AS patients and controls, were calculated using logistic regression. Risk factors for malignancies within the AS cohort were evaluated in the same manner. Results: This study comprised 5825 AS patients and 28,356 matched controls. There was a higher overall risk of cancer in AS patients compared to controls (OR = 1.4, 95% CI 1.24\u20131.6), specifically for solid malignancies (OR = 1.5, 95% CI 1.3\u20131.7), CNS (OR = 3.72, 95% CI 1.29\u201310.7), kidney (OR = 2.06, 95% CI 1.12\u20133.8), and malignancy of unknown primary (OR = 3.06, 95% CI 2.35\u20133.98). Regarding predictors for malignancy within AS patients, older age at diagnosis (OR = 1.31, 95%,CI 1.25\u20132.36), diabetes (OR = 1.52, 95% CI 1.18\u20131.97), IBD (OR = 2.61, 95% CI 1.75\u20133.89), and treatment with DMARDs (OR = 2.17, 95% CI 1.65\u20132.83) were associated with a higher risk of solid malignancies, while NSAIDs treatment alone had a protective effect for solid malignancies (OR = 0.78, 95% CI 0.61\u20130.99). No significant association was found between anti-TNF therapy and the risk of solid or hematologic malignancies within the AS group. Conclusion: AS is associated with an increased risk of overall and site-specific malignancies, with independently higher risk for older age, comorbidity of DM, IBD, and treatment with DMARDs.<\/jats:p>","DOI":"10.3390\/jcm12155153","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T06:38:48Z","timestamp":1691390328000},"page":"5153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The Risk and Predictors of Malignancies in Ankylosing Spondylitis Patients in Israel\u2014A Retrospective Electronic Data-Based Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8150-4494","authenticated-orcid":false,"given":"Polina","family":"Kagan","sequence":"first","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3980-4626","authenticated-orcid":false,"given":"Noy","family":"Horesh","sequence":"additional","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5406-7716","authenticated-orcid":false,"given":"Howard","family":"Amital","sequence":"additional","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1564-6395","authenticated-orcid":false,"given":"Avishai","family":"Tsur","sequence":"additional","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"},{"name":"Israel Defense Forces, Medical Corps, Tel Hashomer, Ramat Gan 9112102, Israel"},{"name":"Department of Military Medicine, Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem 7610001, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1404-8027","authenticated-orcid":false,"given":"Abdulla","family":"Watad","sequence":"additional","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"},{"name":"Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds LS7 4SA, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arnon","family":"Cohen","sequence":"additional","affiliation":[{"name":"Chief Physician\u2019s Office, Clalit Health Services, Tel-Aviv 6209813, Israel"},{"name":"Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva 8410501, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4721-2003","authenticated-orcid":false,"given":"Niv","family":"Ben-Shabat","sequence":"additional","affiliation":[{"name":"Department of Medicine B, Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Tel-Hashomer 5262100, Israel"},{"name":"Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,7]]},"reference":[{"key":"ref_1","first-page":"1635","article-title":"Ankylosing spondylitis","volume":"121","author":"Laitinen","year":"2005","journal-title":"Duodecim"},{"key":"ref_2","first-page":"431","article-title":"Ankylosing spondylitis: An overview","volume":"19","author":"Cornell","year":"2004","journal-title":"Prof. Nurse"},{"key":"ref_3","unstructured":"Goldberger, N., Aburbeh, M., and Haklai, Z. (2021). Leading Causes of Death in Israel 2000-2018."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1159\/000497191","article-title":"General Aspects of Primary Cancer Prevention","volume":"37","author":"Krstic","year":"2019","journal-title":"Dig. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1186\/s12199-018-0740-1","article-title":"Inflammation and cancer","volume":"23","author":"Murata","year":"2018","journal-title":"Environ. Health Prev. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1016\/S0140-6736(00)04046-0","article-title":"Inflammation and cancer: Back to Virchow?","volume":"357","author":"Balkwill","year":"2001","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1016\/j.autrev.2017.07.022","article-title":"Cancer and autoimmune diseases","volume":"16","author":"Giat","year":"2017","journal-title":"Autoimmun. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1007\/s10067-017-3676-8","article-title":"Malignancy as a comorbidity in rheumatic diseases: A retrospective hospital-based study","volume":"37","author":"Wang","year":"2017","journal-title":"Clin. Rheumatol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Dar, L., Ben-Shabat, N., Tiosano, S., Watad, A., McGonagle, D., Komaneshter, D., Cohen, A., Bragazzi, N.L., and Amital, H. (2021). The Incidence and Predictors of Solid- and Hematological Malignancies in Patients with Giant Cell Arteritis: A Large Real-World Database Study. Int. J. Environ. Res. Public Health, 18.","DOI":"10.3390\/ijerph18147595"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e12929","DOI":"10.1111\/ijcp.12929","article-title":"Coexistent malignant conditions in rheumatoid arthritis\u2014A population-based cross-sectional study","volume":"71","author":"Dagan","year":"2017","journal-title":"Int. J. Clin. Pract."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1007\/s12026-016-8885-8","article-title":"Correlation between systemic lupus erythematosus and malignancies: A cross-sectional population-based study","volume":"65","author":"Azrielant","year":"2017","journal-title":"Immunol. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.3892\/ol.2017.6368","article-title":"Ankylosing spondylitis and the risk of cancer","volume":"14","author":"Chang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1741","DOI":"10.1007\/s00296-019-04408-3","article-title":"Malignancy risk in Korean male patients with ankylosing spondylitis","volume":"39","author":"Nam","year":"2019","journal-title":"Rheumatol. Int."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"32063","DOI":"10.1038\/srep32063","article-title":"Risk of malignancy in ankylosing spondylitis: A systematic review and meta-analysis","volume":"6","author":"Deng","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Ben-Shabat, N., Watad, A., Shabat, A., Bragazzi, N.L., Comaneshter, D., Cohen, A.D., and Amital, H. (2020). Low Vitamin D Levels Predict Mortality in Ankylosing Spondylitis pateints: A nationwide population-base cohort study. Nutrients, 12.","DOI":"10.3390\/nu12051400"},{"key":"ref_16","unstructured":"Conway, D.I., McMahon, A.D., Brown, D., and Leyland, A.H. (2019). Measuring Socioeconomic Status and Inequalities, No. 168."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"301","DOI":"10.3109\/03009742.2013.863969","article-title":"Increased risk of cancer for patients with ankylosing spondylitis: A nationwide population-based retrospective cohort study","volume":"43","author":"Sun","year":"2014","journal-title":"Scand. J. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1080\/03009742.2020.1804612","article-title":"Risk of cancer in patients with ankylosing spondylitis: A nationwide cohort study in Taiwan","volume":"50","author":"Chan","year":"2021","journal-title":"Scand. J. Rheumatol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/jphs.12212","article-title":"Evaluation of the comorbidity burden in patients with ankylosing spondylitis treated with tumour necrosis factor inhibitors using a large administrative claims data set","volume":"9","author":"Walsh","year":"2018","journal-title":"J. Pharm. Health Serv. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1136\/ard.2002.004721","article-title":"Cancer incidence among patients with ankylosing spondylitis in Sweden 1965-95: A population based cohort study","volume":"62","author":"Feltelius","year":"2003","journal-title":"Ann. Rheum. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1282","DOI":"10.1002\/art.38339","article-title":"Ankylosing spondylitis, psoriatic arthritis, and risk of malignant lymphoma: A cohort study based on nationwide prospectively recorded data from Sweden","volume":"66","author":"Hellgren","year":"2014","journal-title":"Arthritis Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s00296-013-2927-5","article-title":"Ankylosing spondylitis and other inflammatory spondyloarthritis increase the risk of developing type 2 diabetes in an Asian population","volume":"34","author":"Chen","year":"2013","journal-title":"Rheumatol. Int."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Heslinga, S.C., Oever, I.A.V.D., Van Sijl, A.M., Peters, M.J., E Van Der Horst-Bruinsma, I., Smulders, Y.M., and Nurmohamed, M.T. (2015). Cardiovascular risk management in patients with active ankylosing spondylitis: A detailed evaluation. BMC Musculoskelet. Disord., 16.","DOI":"10.1186\/s12891-015-0532-3"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S5","DOI":"10.4065\/mcp.2010.0467","article-title":"A Physiologic and Pharmacological Basis for Implementation of Incretin Hormones in the Treatment of Type 2 Diabetes Mellitus","volume":"85","author":"Freeman","year":"2010","journal-title":"Mayo Clin. Proc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"i3","DOI":"10.1093\/annonc\/mdl443","article-title":"Epidemiology of hematological malignancies","volume":"18","author":"Bordoni","year":"2007","journal-title":"Ann. Oncol."},{"key":"ref_26","first-page":"3817","article-title":"Risks of solid cancers in elderly persons with osteoarthritis or ankylosing spondylitis","volume":"59","author":"Michael","year":"2020","journal-title":"Rheumatol. Int."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ijc.2910590307","article-title":"Cancer mortality following X-ray treatment for ankylosing spondylitis","volume":"59","author":"Weiss","year":"1994","journal-title":"Int. J. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2262","DOI":"10.1016\/j.juro.2012.12.014","article-title":"Autoimmune Disease and Subsequent Urological Cancer","volume":"189","author":"Liu","year":"2013","journal-title":"J. Urol."},{"key":"ref_29","first-page":"93","article-title":"Risk of renal cancer in patients with inflammatory bowel disease: A pooled analysis of population-based studies","volume":"39","author":"Feng","year":"2020","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1093\/ecco-jcc\/jjx040","article-title":"Cancer Risk in the Early Stages of Inflammatory Bowel Disease in Korean Patients: A Nationwide Population-based Study","volume":"11","author":"Jung","year":"2017","journal-title":"J. Crohn\u2019s Colitis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.1002\/ijc.29657","article-title":"Risk of cancer of unknown primary after hospitalization for autoimmune diseases","volume":"137","author":"Hemminki","year":"2015","journal-title":"Int. J. Cancer"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/ije\/dym193","article-title":"Colorectal cancer risk, chronic illnesses, operations and medications: Case-control results from the Melbourne colorectal cancer study","volume":"36","author":"Kune","year":"2007","journal-title":"Int. J. Epidemiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1136\/gut.2009.203000","article-title":"Effect of aspirin and NSAIDs on risk and survival from colorectal cancer","volume":"59","author":"Din","year":"2010","journal-title":"Gut"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(10)62110-1","article-title":"Effect of daily aspirin on long-term risk of death due to cancer: Analysis of individual patient data from randomised trials","volume":"377","author":"Rothwell","year":"2011","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"149185","DOI":"10.1155\/2014\/149185","article-title":"Chronic inflammation and cytokines in the tumor microenvironment","volume":"2014","author":"Landskron","year":"2014","journal-title":"J. Immunol. Res."},{"key":"ref_36","first-page":"252","article-title":"Nonsteroidal Anti-inflammatory Drugs as Anticancer Agents: Mechanistic, Pharmacologic, and Clinical Issues","volume":"94","author":"Thun","year":"2002","journal-title":"Gynecol. Oncol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1038\/nrrheum.2012.41","article-title":"Genetics of spondyloarthritis\u2014Beyond the MHC","volume":"8","author":"Reveille","year":"2012","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.semarthrit.2018.05.009","article-title":"Malignancy development risk in psoriatic arthritis patients undergoing treatment: A systematic review and meta-analysis","volume":"48","author":"Luo","year":"2018","journal-title":"Semin. Arthritis Rheum."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"R45","DOI":"10.1186\/ar2404","article-title":"Research article A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis","volume":"10","author":"Smitten","year":"2008","journal-title":"Arthritis Res. Ther."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1080\/14740338.2016.1238458","article-title":"Risk of malignancies using anti-TNF agents in rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis: A systematic review and meta-analysis","volume":"15","author":"Bonovas","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1136\/annrheumdis-2016-209270","article-title":"Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: A collaborative study from the ARTIS and DANBIO registers","volume":"76","author":"Hellgren","year":"2016","journal-title":"Ann. Rheum. Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1136\/annrheumdis-2011-201244","article-title":"Adalimumab: Long-term safety in 23 458 patients from global clinical trials in rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, psoriasis and Crohn\u2019s disease","volume":"72","author":"Burmester","year":"2012","journal-title":"Ann. Rheum. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1007\/s10067-018-4037-y","article-title":"Ischemic heart disease and ankylosing spondylitis\u2014Assessing the role of inflammation","volume":"37","author":"Shuster","year":"2018","journal-title":"Clin. Rheumatol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1614","DOI":"10.1002\/acr.24616","article-title":"Mortality in Ankylosing Spondylitis According to Treatment: A Nationwide Retrospective Cohort Study of 5,900 Patients From Israel","volume":"74","author":"Shabat","year":"2021","journal-title":"Arthritis Care Res."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/15\/5153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:27:01Z","timestamp":1760128021000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/15\/5153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,7]]},"references-count":44,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2023,8]]}},"alternative-id":["jcm12155153"],"URL":"https:\/\/doi.org\/10.3390\/jcm12155153","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2023,8,7]]}}}