{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T20:19:24Z","timestamp":1776889164378,"version":"3.51.2"},"reference-count":38,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Cancer Institute","award":["ZIA CP010136"],"award-info":[{"award-number":["ZIA CP010136"]}]},{"name":"National Cancer Institute","award":["P30 AR079369"],"award-info":[{"award-number":["P30 AR079369"]}]},{"name":"NIH\/NIAMS","award":["ZIA CP010136"],"award-info":[{"award-number":["ZIA CP010136"]}]},{"name":"NIH\/NIAMS","award":["P30 AR079369"],"award-info":[{"award-number":["P30 AR079369"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Immune dysregulation is thought to increase the risk of non-Hodgkin lymphoma (NHL), but the evidence varies by subtype. We evaluated whether antinuclear antibodies (ANA), double-stranded DNA antibodies (anti-dsDNA), and extractable nuclear antigen antibodies (anti-ENA) were associated with the risk of common NHL subtypes in a nested case-control study. The autoantibodies were tested in serum collected years prior to NHL diagnosis in 832 cases and 809 controls from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Logistic regression was used to determine odds ratios (ORs) and 95% confidence intervals (95% CI) for the association with NHL risk. No association was observed between ANA positivity and NHL risk overall (OR: 1.18, 95% CI: 0.88\u20131.58); however, ANA positivity was associated with an increased risk of diffuse large B-cell lymphoma (DLBCL) (OR: 1.83, 95% CI: 1.15\u20132.91), with 19.7% of cases and 12.2% of controls testing positive. The presence of either anti-ENA or anti-dsDNA was associated with an increased risk of NHL (OR: 2.93, 95% CI: 1.18\u20137.28), particularly DLBCL (OR: 3.51, 95% CI: 1.02\u201312.0) and marginal zone lymphoma (OR: 8.86, 95% CI: 1.26\u201362.0). Our study demonstrates that autoantibodies are associated with an elevated risk of DLBCL, providing support for autoimmunity as a risk factor.<\/jats:p>","DOI":"10.3390\/cancers15215231","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T12:48:31Z","timestamp":1698756511000},"page":"5231","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antinuclear Antibodies Are Associated with an Increased Risk of Diffuse Large B-Cell Lymphoma"],"prefix":"10.3390","volume":"15","author":[{"given":"Eleanor","family":"Frost","sequence":"first","affiliation":[{"name":"Department of Epidemiology & Population Health, Stanford University School of Medicine, Stanford, CA 94305, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan N.","family":"Hofmann","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Yi","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine G.","family":"Parks","sequence":"additional","affiliation":[{"name":"Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health and Department of Health and Human Services, Research Triangle Park, Durham, NC 27709, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashley A.","family":"Frazer-Abel","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin D.","family":"Deane","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Colorado Anschutz Medical Campus, Denver, CO 80045, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja I.","family":"Berndt","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"ref_1","unstructured":"Cerhan, J.R., Vajdic, C.M., and Spinelli, J.J. (2017). Cancer Epidemiology and Prevention, Oxford University Press. [4th ed.]."},{"key":"ref_2","first-page":"1884","article-title":"Autoimmune disease is a risk factor for the development of non-Hodgkin\u2019s lymphoma","volume":"32","author":"Cuttner","year":"2005","journal-title":"J. Rheumatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2337","DOI":"10.1001\/archinte.165.20.2337","article-title":"The risk of lymphoma development in autoimmune diseases: A meta-analysis","volume":"165","author":"Zintzaras","year":"2005","journal-title":"Arch. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1002\/ijc.24287","article-title":"Population-based study of autoimmune conditions and the risk of specific lymphoid malignancies","volume":"125","author":"Anderson","year":"2009","journal-title":"Int. J. Cancer"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2025","DOI":"10.1093\/annonc\/mdu365","article-title":"Autoimmune diseases associated with non-Hodgkin lymphoma: A nationwide cohort study","volume":"25","author":"Fallah","year":"2014","journal-title":"Ann. Oncol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1158\/1055-9965.EPI-13-0695","article-title":"Prior autoimmune disease and risk of monoclonal gammopathy of undetermined significance and multiple myeloma: A systematic review","volume":"23","author":"McShane","year":"2014","journal-title":"Cancer Epidemiol. Biomark. Prev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.semcancer.2013.12.001","article-title":"Lymphoma development in patients with autoimmune and inflammatory disorders--what are the driving forces?","volume":"24","author":"Baecklund","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1093\/jncimonographs\/lgu013","article-title":"Etiologic heterogeneity among non-Hodgkin lymphoma subtypes: The InterLymph Non-Hodgkin Lymphoma Subtypes Project","volume":"48","author":"Morton","year":"2014","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1007\/s00277-018-3515-2","article-title":"Autoimmune disease-associated non-Hodgkin\u2019s lymphoma-a large retrospective study from China","volume":"98","author":"Hu","year":"2019","journal-title":"Ann. Hematol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2319","DOI":"10.1002\/art.34380","article-title":"Prevalence and sociodemographic correlates of antinuclear antibodies in the United States","volume":"64","author":"Satoh","year":"2012","journal-title":"Arthritis Rheum."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/art.41214","article-title":"Increasing Prevalence of Antinuclear Antibodies in the United States","volume":"72","author":"Dinse","year":"2020","journal-title":"Arthritis Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.jaut.2009.09.008","article-title":"Recent insights in the epidemiology of autoimmune diseases: Improved prevalence estimates and understanding of clustering of diseases","volume":"33","author":"Cooper","year":"2009","journal-title":"J. Autoimmun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1421","DOI":"10.1001\/archinte.1996.00440120079007","article-title":"Antinuclear antibody testing. A study of clinical utility","volume":"156","author":"Slater","year":"1996","journal-title":"Arch. Intern. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1080\/03009740701406577","article-title":"Increased titres of anti-nuclear antibodies do not predict the development of associated disease in the absence of initial suggestive signs and symptoms","volume":"36","author":"Dinser","year":"2007","journal-title":"Scand. J. Rheumatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.3389\/fimmu.2019.01476","article-title":"Lifetime Pesticide Use and Antinuclear Antibodies in Male Farmers from the Agricultural Health Study","volume":"10","author":"Parks","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1136\/oemed-2022-108266","article-title":"Occupational trichloroethylene exposure and antinuclear antibodies: A cross-sectional study in China","volume":"79","author":"Purdue","year":"2022","journal-title":"Occup. Environ. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1046\/j.1365-2141.2003.04587.x","article-title":"Prevalence and pattern of antinuclear autoantibodies in 347 patients with non-Hodgkin\u2019s lymphoma","volume":"123","author":"Guyomard","year":"2003","journal-title":"Br. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1111\/j.1365-3083.2008.02095.x","article-title":"Autoimmune markers in lymphoid malignancies","volume":"67","author":"Roth","year":"2008","journal-title":"Scand. J. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"117","DOI":"10.3109\/10428199209053610","article-title":"Autoantibodies in the sera of patients with lymphoma","volume":"7","author":"Swissa","year":"1992","journal-title":"Leuk. Lymphoma"},{"key":"ref_20","first-page":"7","article-title":"Clinical significance of elevated antinuclear antibody test in patients with Hodgkin\u2019s and Non-Hodgkin\u2019s lymphoma: A single center experience","volume":"99","author":"Altintas","year":"2008","journal-title":"Minerva Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e90","DOI":"10.1182\/blood-2010-06-289561","article-title":"InterLymph hierarchical classification of lymphoid neoplasms for epidemiologic research based on the WHO classification (2008): Update and future directions","volume":"116","author":"Turner","year":"2010","journal-title":"Blood"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"212","DOI":"10.2174\/1574887110666150730121429","article-title":"The PLCO Biorepository: Creating, Maintaining, and Administering a Unique Biospecimen Resource","volume":"10","author":"Carrick","year":"2015","journal-title":"Rev. Recent Clin. Trials"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1007\/BF00051339","article-title":"Prior medical conditions and the risk of adult leukemia in Shanghai, People\u2019s Republic of China","volume":"4","author":"Zheng","year":"1993","journal-title":"Cancer Causes Control"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1182\/blood-2005-11-4620","article-title":"Patterns of autoimmunity and subsequent chronic lymphocytic leukemia in Nordic countries","volume":"108","author":"Landgren","year":"2006","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.canep.2019.02.014","article-title":"The impact of rheumatological disorders on lymphomas and myeloma: A report on risk and survival from the UK\u2019s population-based Haematological Malignancy Research Network","volume":"59","author":"Kane","year":"2019","journal-title":"Cancer Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1093\/jncimonographs\/lgu001","article-title":"Medical history, lifestyle, family history, and occupational risk factors for chronic lymphocytic leukemia\/small lymphocytic lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project","volume":"48","author":"Slager","year":"2014","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/jncimonographs\/lgu010","article-title":"Medical history, lifestyle, family history, and occupational risk factors for diffuse large B-cell lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project","volume":"48","author":"Cerhan","year":"2014","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1093\/jncimonographs\/lgu011","article-title":"Medical history, lifestyle, family history, and occupational risk factors for marginal zone lymphoma: The InterLymph Non-Hodgkin Lymphoma Subtypes Project","volume":"48","author":"Bracci","year":"2014","journal-title":"J. Natl. Cancer Inst. Monogr."},{"key":"ref_29","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":"Smedby","year":"2008","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1186\/s13075-021-02692-8","article-title":"Hematological malignancies in systemic lupus erythematosus: Clinical characteristics, risk factors, and prognosis-a case-control study","volume":"24","author":"Zhang","year":"2022","journal-title":"Arthritis Res. Ther."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Barreno-Rocha, S.G., Guzm\u00e1n-Silahua, S., Cardona-Mu\u00f1oz, E.G., Zavala-Cerna, M.G., Mu\u00f1oz Gaytan, D.E., Riebeling-Navarro, C., Rubio-Jurado, B., and Nava-Zavala, A.H. (2023). Frequency of Autoantibodies on Non-Hodgkin Lymphoma. Healthcare, 11.","DOI":"10.3390\/healthcare11152210"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"213","DOI":"10.4103\/0973-1482.183559","article-title":"Clinical significance of elevated antinuclear antibodies in patients with diffuse large B-cell lymphoma: A single center study","volume":"14","author":"Lang","year":"2018","journal-title":"J. Cancer Res. Ther."},{"key":"ref_33","first-page":"502","article-title":"The prevalence and significance of autoantibodies in patients with non-Hodgkin\u2019s lymphoma: Are they correlated with clinicopathological features?","volume":"17","author":"Bilici","year":"2012","journal-title":"J. BUON"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.autrev.2018.09.003","article-title":"Novel autoantibodies in Sj\u00f6gren\u2019s syndrome: A comprehensive review","volume":"18","year":"2019","journal-title":"Autoimmun. Rev."},{"key":"ref_35","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_36","doi-asserted-by":"crossref","first-page":"e3766","DOI":"10.1097\/MD.0000000000003766","article-title":"Predicting the risk for lymphoma development in Sj\u00f6gren syndrome: An easy tool for clinical use","volume":"95","author":"Fragkioudaki","year":"2016","journal-title":"Medicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1093\/aje\/kwk075","article-title":"Evidence of a healthy volunteer effect in the prostate, lung, colorectal, and ovarian cancer screening trial","volume":"165","author":"Pinsky","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"443","DOI":"10.3322\/caac.21357","article-title":"2016 US lymphoid malignancy statistics by World Health Organization subtypes","volume":"66","author":"Teras","year":"2016","journal-title":"CA Cancer J. Clin."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/21\/5231\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:14:45Z","timestamp":1760130885000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/15\/21\/5231"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,31]]},"references-count":38,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["cancers15215231"],"URL":"https:\/\/doi.org\/10.3390\/cancers15215231","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,31]]}}}