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Oncol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies suggested that systemic lupus erythematosus (SLE) might be associated with increased cancer incidence and cancer-related death, however, the results are inconsistent. We aim to comprehensively estimate the causal relationships between SLE and cancer morbidity and mortality using a meta-analysis of cohort studies and Mendelian randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic search was conducted using PubMed to identify cohort studies published before January 21, 2021. Meta-analysis was performed to calculate relative risk (RR) and corresponding 95% confidence intervals (CI). In addition, we further evaluated the potentially causal relationships identified by cohort studies using two-sample Mendelian randomization.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 48 cohort studies involving 247,575 patients were included. We performed 31 main meta-analysis to assess the cancer risk and three meta-analyses to evaluate cancer mortality in SLE patients. Through meta-analyses, we observed an increased risk of overall cancer (RR=1.62, 95%CI, 1.47-1.79, <jats:italic>P<\/jats:italic>&amp;lt;0.001) and cancer-related death (RR=1.52, 95%CI, 1.36-1.70, <jats:italic>P<\/jats:italic>&amp;lt;0.001) in patients with SLE. Subgroup analysis by site-specific cancer showed that SLE was a risk factor for 17 site-specific cancers, including six digestive cancers (esophagus, colon, anus, hepatobiliary, liver, pancreatic), five hematologic cancers (lymphoma, Hodgkin\u2019s lymphoma, non-Hodgkin lymphoma, leukemia, multiple myeloma), as well as cancer in lung, larynx, cervical, vagina\/vulva, renal, bladder, skin, and thyroid. In addition, further mendelian randomization analysis verified a weakly association between genetically predisposed SLE and lymphoma risk (odds ratio=1.0004, <jats:italic>P<\/jats:italic>=0.0035).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Findings from our study suggest an important role of SLE in carcinogenesis, especially for lymphoma.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:uri>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:uri>, CRD42021243635.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2022.860794","type":"journal-article","created":{"date-parts":[[2022,5,4]],"date-time":"2022-05-04T07:49:15Z","timestamp":1651650555000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":57,"title":["Association Between Systemic Lupus Erythematosus and Cancer Morbidity and Mortality: Findings From Cohort Studies"],"prefix":"10.3389","volume":"12","author":[{"given":"Min","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhou","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye","family":"Bai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongqing","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30237-5","article-title":"Management Strategies and Future Directions for Systemic Lupus Erythematosus in Adults","volume":"393","author":"Durcan","year":"2019","journal-title":"Lancet"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1002\/art.24835","article-title":"Population-Based Lupus Registries: Advancing Our Epidemiologic Understanding","volume":"61","author":"Lim","year":"2009","journal-title":"Arthritis Rheum"},{"key":"B3","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1136\/ard.2007.070367","article-title":"EULAR Recommendations for the Management of Systemic Lupus Erythematosus. 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