{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T16:13:34Z","timestamp":1789143214844,"version":"build-2803163510"},"reference-count":27,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"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>Objective: To evaluate cancer risk among individuals with connective tissue disease (CTD) in Friuli Venezia Giulia, northern Italy. Methods: A population-based cohort study was conducted based on data from health records available in the regional healthcare database. Demographic characteristics, hospital discharges, exemption from medical charges, drug prescriptions, were individually matched with data from the population-based cancer registry. Cancer risk was assessed in people diagnosed with the following diseases: systemic lupus erythematosus (SLE), Sj\u00f6gren\u2019s syndrome (SS), systemic sclerosis (SSc), polymyositis (PM), and dermatomyositis (DM). Results: In all, 2504 patients were followed for a total of 18,006 person-years (median follow-up: 6.8 years). After 5 and 10 years of follow-up, the cumulative cancer incidence was 2.6% and 8.5%, respectively. The most common cancers were breast (n = 34), lung (n = 24), colon\u2013rectum\u2013anus (n = 20), and non-Hodgkin lymphomas (NHL) (n = 20). Overall, no excess cancer risk was noted (SIR = 0.87), whereas the number of observed NHL cases was more than two-fold significantly higher than expected (SIR = 2.52). The subgroup analysis showed a higher risk of NHL among SS patients (SIR = 3.84) and SLE patients (SIR = 2.69). Conversely, the study population showed a decreased risk for breast cancers (SIR = 0.61) and corpus uteri (SIR = 0.21). Conclusions: The incidence of NHL was higher among patients with SS and SLE. Careful surveillance for hematological malignancies in these patients is recommended.<\/jats:p>","DOI":"10.3390\/jcm11154272","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:53:45Z","timestamp":1658494425000},"page":"4272","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Risk of Cancer in Connective Tissue Diseases in Northeastern Italy over 15 Years"],"prefix":"10.3390","volume":"11","author":[{"given":"Elena","family":"Treppo","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Academic Hospital \u201cSanta Maria della Misericordia\u201d, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2907-0745","authenticated-orcid":false,"given":"Federica","family":"Toffolutti","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Manfr\u00e8","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Academic Hospital \u201cSanta Maria della Misericordia\u201d, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6731-7569","authenticated-orcid":false,"given":"Martina","family":"Taborelli","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ginevra","family":"De Marchi","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Academic Hospital \u201cSanta Maria della Misericordia\u201d, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"De Vita","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Academic Hospital \u201cSanta Maria della Misericordia\u201d, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diego","family":"Serraino","sequence":"additional","affiliation":[{"name":"Unit of Cancer Epidemiology, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy"},{"name":"Friuli Venezia Giulia Cancer Registry, Centro di Riferimento Oncologico di Aviano (CRO), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Via F. Gallini 2, 33081 Aviano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0134-6439","authenticated-orcid":false,"given":"Luca","family":"Quartuccio","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Academic Hospital \u201cSanta Maria della Misericordia\u201d, Azienda Sanitaria Universitaria Friuli Centrale (ASUFC), 33100 Udine, Italy"},{"name":"Department of Medicine (DAME), University of Udine, Via Colugna 50, 33100 Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/joim.12395","article-title":"Human Autoimmune Diseases: A Comprehensive Update","volume":"278","author":"Wang","year":"2015","journal-title":"J. Intern. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.semcancer.2019.06.005","article-title":"Autoimmune Diseases and Hematological Malignancies: Exploring the Underlying Mechanisms from Epidemiological Evidence","volume":"64","author":"Hemminki","year":"2020","journal-title":"Semin. Cancer Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4029","DOI":"10.1182\/blood-2007-10-119974","article-title":"Autoimmune Disorders and Risk of Non-Hodgkin Lymphoma Subtypes: A Pooled Analysis within the InterLymph Consortium","volume":"111","author":"Vajdic","year":"2008","journal-title":"Blood"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"594096","DOI":"10.3389\/fimmu.2020.594096","article-title":"Primary Sj\u00f6gren\u2019s Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development","volume":"11","author":"Goules","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1080\/03009740252937568","article-title":"Increased Cancer Incidence in a Swedish Cohort of Patients with Systemic Lupus Erythematosus","volume":"31","author":"Yin","year":"2002","journal-title":"Scand. J. Rheumatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1002\/art.21675","article-title":"Association of Chronic Inflammation, Not Its Treatment, with Increased Lymphoma Risk in Rheumatoid Arthritis","volume":"54","author":"Baecklund","year":"2006","journal-title":"Arthritis Rheum."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1136\/annrheumdis-2012-202099","article-title":"Lymphoma Risk in Systemic Lupus: Effects of Disease Activity versus Treatment","volume":"73","author":"Bernatsky","year":"2014","journal-title":"Ann. Rheum. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/BOR.0b013e32834a5081","article-title":"Cancer and Systemic Sclerosis: Novel Insights into Pathogenesis and Clinical Implications","volume":"23","author":"Shah","year":"2011","journal-title":"Curr. Opin. Rheumatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.1093\/rheumatology\/keab166","article-title":"A Systematic Review and Meta-Analysis to Inform Cancer Screening Guidelines in Idiopathic Inflammatory Myopathies","volume":"60","author":"Oldroyd","year":"2021","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"101472","DOI":"10.1016\/j.berh.2019.101472","article-title":"The Relationships between Cancer and Autoimmune Rheumatic Diseases","volume":"34","author":"Cappelli","year":"2020","journal-title":"Best Pract. Res. Clin. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"282","DOI":"10.3899\/jrheum.140566","article-title":"Polymyositis\/Dermatomyositis and Malignancy Risk: A Metaanalysis Study","volume":"42","author":"Yang","year":"2015","journal-title":"J. Rheumatol."},{"key":"ref_13","first-page":"100","article-title":"Malignancies in Wegener\u2019s Granulomatosis: Incidence and Relation to Cyclophosphamide Therapy in a Cohort of 293 Patients","volume":"35","author":"Faurschou","year":"2008","journal-title":"J. Rheumatol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"f1939","DOI":"10.1136\/bmj.f1939","article-title":"ARTIS Study Group Rheumatoid Arthritis, Anti-Tumour Necrosis Factor Therapy, and Risk of Malignant Melanoma: Nationwide Population Based Prospective Cohort Study from Sweden","volume":"346","author":"Raaschou","year":"2013","journal-title":"BMJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1093\/rheumatology\/ker407","article-title":"Cryoglobulinaemia Related to Sjogren\u2019s Syndrome or HCV Infection: Differences Based on the Pattern of Bone Marrow Involvement, Lymphoma Evolution and Laboratory Tests after Parotidectomy","volume":"51","author":"Quartuccio","year":"2012","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1019","DOI":"10.1016\/j.autrev.2015.07.002","article-title":"Anti-SSA\/SSB-Negative Sj\u00f6gren\u2019s Syndrome Shows a Lower Prevalence of Lymphoproliferative Manifestations, and a Lower Risk of Lymphoma Evolution","volume":"14","author":"Quartuccio","year":"2015","journal-title":"Autoimmun. Rev."},{"key":"ref_17","first-page":"150","article-title":"The Evaluation of Disease Activity in Sj\u00f6gren\u2019s Syndrome Based on the Degree of MALT Involvement: Glandular Swelling and Cryoglobulinaemia Compared to ESSDAI in a Cohort Study","volume":"36","author":"Gandolfo","year":"2018","journal-title":"Clin. Exp. Rheumatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1002\/ijc.25680","article-title":"Non-Hodgkin Lymphoma and Autoimmunity: Does Gender Matter?","volume":"129","author":"Ansell","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Chatzis, L., Pezoulas, V.C., Ferro, F., Gandolfo, S., Donati, V., Binutti, M., Callegher, S.Z., Venetsanopoulou, A., Zampeli, E., and Mavrommati, M. (2020). Sj\u00f6gren\u2019s Syndrome: The Clinical Spectrum of Male Patients. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082620"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/j.autrev.2014.03.001","article-title":"Increased Risk of High Grade Cervical Squamous Intraepithelial Lesions in Systemic Lupus Erythematosus: A Meta-Analysis of the Literature","volume":"13","author":"Zard","year":"2014","journal-title":"Autoimmun. Rev."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1007\/s10067-010-1606-0","article-title":"Systemic Lupus Erythematosus, Human Papillomavirus Infection, Cervical Pre-Malignant and Malignant Lesions: A Systematic Review","volume":"30","author":"Santana","year":"2011","journal-title":"Clin. Rheumatol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1002\/1097-0142(195311)6:6<1147::AID-CNCR2820060605>3.0.CO;2-L","article-title":"Pulmonary Fibrosis and Terminal Bronchiolar (Alveolar-Cell) Carcinoma in Scleroderma","volume":"6","author":"Zatuchni","year":"1953","journal-title":"Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1002\/art.39022","article-title":"Examination of Autoantibody Status and Clinical Features Associated with Cancer Risk and Cancer-Associated Scleroderma","volume":"67","author":"Shah","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1002\/acr.24076","article-title":"Incidence, Risk Factors, and Outcomes of Cancer in Systemic Sclerosis","volume":"72","author":"Morrisroe","year":"2020","journal-title":"Arthritis Care Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1588084","DOI":"10.1080\/2162402X.2019.1588084","article-title":"Autoantibody Status in Systemic Sclerosis Patients Defines Both Cancer Risk and Survival with ANA Negativity in Cases with Concomitant Cancer Having a Worse Survival","volume":"8","author":"Watad","year":"2019","journal-title":"Oncoimmunology"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1093\/rheumatology\/kev196","article-title":"The Evolving Paradigm of Cancer Risk Related to Cyclophosphamide Therapy in Granulomatosis with Polyangiitis","volume":"54","author":"Calatroni","year":"2015","journal-title":"Rheumatol. Oxf. Engl."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000353138","article-title":"Breast Cancer in Systemic Lupus Erythematosus","volume":"85","author":"Clarke","year":"2013","journal-title":"Oncology"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/15\/4272\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:54:57Z","timestamp":1760140497000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/11\/15\/4272"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":27,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["jcm11154272"],"URL":"https:\/\/doi.org\/10.3390\/jcm11154272","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}