Abstract
Autoimmune conditions reflect dysregulation of the immune system; this may be of clinical significance in the development of several malignancies. Previous studies show an association between systemic lupus erythematosus (SLE) and the development of malignancies; however, their investigations into the development of specific malignancies are inconsistent, and their external validity may be questionable. The main objective of this study is to investigate the association between the presence of SLE and various malignancies, in a large-scale population-based study. Data for this study was collected from Clalit Health Services, the largest state-mandated health service organization in Israel. All adult members diagnosed with SLE were included (n = 5018) and their age and sex-matched controls (n = 25,090), creating a cross-sectional population-based study. Medical records of all subjects were analyzed for documentation of malignancies. Logistic regression models were built separately for each malignant condition, controlling for age, gender, BMI, smoking, and socioeconomic status. Diagnosis of malignancy (of any type) was more prevalent in the SLE population (odds ratio [OR] 3.35, 95% confidence interval [CI] 3.02–3.72). SLE diagnosis was also found to be independently associated with higher proportions of non-Hodgkin lymphoma (OR 3.02, 95% CI 2.72–3.33), Hodgkin lymphoma (OR 2.43, 95% CI 1.88–2.99), multiple myeloma (OR 2.57, 95% CI 1.85–3.28), cervix uteri malignancies (OR 1.65, 95% CI 1.10–2.20), and genital organ malignancies (OR 2.32, 95% CI 1.42–3.22), after adjustment for confounding variables. The presence of an SLE diagnosis was found to be independently associated with higher proportions of malignancies, particularly hematologic malignancies. These findings should be considered while treating SLE patients, and possibly supplement their screening routine.
Similar content being viewed by others
References
De Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37.
Abu-Shakra M, Buskila D, Ehrenfeld M, et al. Cancer and autoimmunity: autoimmune and rheumatic features in patients with malignancies. Ann Rheum Dis. 2001;60:433–41.
Pludowski P, Holick MF, Pilz S, et al. Vitamin D effects on musculoskeletal health, immunity, autoimmunity, cardiovascular disease, cancer, fertility, pregnancy, dementia and mortality—a review of recent evidence. Autoimmun Rev. 2013;12:976–89.
Askling J, Bongartz T. Malignancy and biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol. 2008;20:334–9.
Bernatsky S, Ramsey-Goldman R, Labrecque J, et al. Cancer risk in systemic lupus: an updated international multi-centre cohort study. J Autoimmun. 2013;42:130–5.
Chen Y, Chang Y, Wang C, et al. The risk of cancer in patients with rheumatoid arthritis: a nationwide cohort study in Taiwan. Arthritis Rheum. 2011;63:352–8.
Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum. 1997;40:1580–6.
Colaci M, Giuggioli D, Sebastiani M, et al. Lung cancer in scleroderma: results from an Italian rheumatologic center and review of the literature. Autoimmun Rev. 2013;12:374–9. doi:10.1016/j.autrev.2012.06.003.
Colaci M, Giuggioli D, Vacchi C, et al. Breast cancer in systemic sclerosis: results of a cross-linkage of an Italian Rheumatologic Center and a population-based Cancer Registry and review of the literature. Autoimmun Rev. 2014;13:132–7. doi:10.1016/j.autrev.2013.09.006.
Fallah M, Liu X, Ji J, et al. Autoimmune diseases associated with non-Hodgkin lymphoma: a nationwide cohort study. Ann Oncol. 2014;25:2025–30.
Gorodetskiy V, Klapper W, Probatova N, et al. Primary diffuse large B-cell lymphoma of the liver in a patient with Sjogren syndrome.
Lopez-Olivo MA, Tayar JH, Martinez-Lopez JA, et al. Risk of malignancies in patients with rheumatoid arthritis treated with biologic therapy: a meta-analysis. JAMA. 2012;308:898–908.
Sigurgeirsson B, Lindelöf B, Edhag O, et al. Risk of cancer in patients with dermatomyositis or polymyositis. N Engl J Med. 1992;326:363–7.
Simon TA, Thompson A, Gandhi KK, et al. Incidence of malignancy in adult patients with rheumatoid arthritis: a meta-analysis. Arthritis Res Ther. 2015;17:212. doi:10.1186/s13075-015-0728-9.
Stockton D, Doherty VR, Brewster DH. Risk of cancer in patients with dermatomyositis or polymyositis, and follow-up implications: a Scottish population-based cohort study. Br J Cancer. 2001;85:41–5. doi:10.1054/bjoc.2001.1699.
Voulgarelis M, Ziakas PD, Papageorgiou A, et al. Prognosis and outcome of non-Hodgkin lymphoma in primary Sjögren syndrome. Medicine (Baltimore). 2012;91:1–9. doi:10.1097/MD.0b013e31824125e4.
Zampieri S, Valente M, Adami N, et al. Polymyositis, dermatomyositis and malignancy: a further intriguing link. Autoimmun Rev. 2010;9:449–53. doi:10.1016/j.autrev.2009.12.005.
Chaiamnuay S, Bertoli AM, Roseman JM, et al. African–American and Hispanic ethnicities, renal involvement and obesity predispose to hypertension in systemic lupus erythematosus: results from LUMINA, a multiethnic cohort (LUMINAXLV). Ann Rheum Dis. 2007;66:618–22.
Skaggs BJ, Hahn BH, McMahon M. Accelerated atherosclerosis in patients with SLE—mechanisms and management. Nat Rev Rheumatol. 2012;8:214–23.
Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52:1481–90.
Bernatsky S, Ramsey-Goldman R, Isenberg D, et al. Hodgkin’s lymphoma in systemic lupus erythematosus. Rheumatology. 2007;46:830–2.
Björnådal L, Löfström B, Yin L, et al. Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus. Scand J Rheumatol. 2002;31:66–71.
Mellemkjér L, Andersen V, Linet MS, et al. Non-Hodgkin’s lymphoma and other cancers among a cohort of patients with systemic lupus erythematosus. Arthritis Rheum. 1997;40:761–8.
Sultan SM, Ioannou Y, Isenberg D a. Is there an association of malignancy with systemic lupus erythematosus? An analysis of 276 patients under long-term review. Rheumatology (Oxford). 2000;39:1147–52.
Cibere J, Sibley J, Haga M. Systemic lupus erythematosus and the risk of malignancy. Lupus. 2001;10:394–400.
Pettersson T, Pukkala E, Teppo L, et al. Increased risk of cancer in patients with systemic lupus erythematosus. Ann Rheum Dis. 1992;51:437–9.
Bieber V, Cohen AD, Freud T, et al. Autoimmune smoke and fire—coexisting rheumatoid arthritis and chronic obstructive pulmonary disease: a cross-sectional analysis. Immunol Res. 2013;56:261–6. doi:10.1007/s12026-013-8395-x.
Guy A, Tiosano S, Comaneshter D, et al. Aortic aneurysm association with SLE—a case–control study. Lupus 2016;0961203316628999.
Levi EH, Watad A, Whitby A, et al. Coexistence of ischemic heart disease and rheumatoid arthritis patients—a case control study. Autoimmun Rev. 2016:4–7. doi:10.1016/j.autrev.2016.01.006.
Watad A, Cohen AD, Comaneshter D, et al. Hyperthyroidism association with SLE, lessons from real-life data—a case–control study. Autoimmunity 2015;1–4.
Smedby KE, Askling J, Mariette X, et al. Autoimmune and inflammatory disorders and risk of malignant lymphomas—an update. J Intern Med. 2008;264:514–27.
Landgren O, Engels EA, Pfeiffer RM, et al. Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia. J Natl Cancer Inst. 2006;98:1321–30. doi:10.1093/jnci/djj361.
Veeranki S, Choubey D. Systemic lupus erythematosus and increased risk to develop B cell malignancies: role of the p200-family proteins. Immunol Lett. 2010;133:1–5.
Xu Y, Wiernik PH. Systemic lupus erythematosus and B-cell hematologic neoplasm. Lupus. 2001;10:841–50. doi:10.1191/096120301701548481.
Barzilai O, Sherer Y, Ram M, et al. Epstein–Barr virus and cytomegalovirus in autoimmune diseases. Ann N Y Acad Sci. 2007;1108:567–77.
Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med. 2003;349:1324–32.
James JA, Neas BR, Moser KL, et al. Systemic lupus erythematosus in adults is associated with previous Epstein-Barr virus exposure. Arthritis Rheum. 2001;44:1122–6.
Müller AMS, Ihorst G, Mertelsmann R, et al. Epidemiology of non-Hodgkin’s lymphoma (NHL): trends, geographic distribution, and etiology. Ann Hematol. 2005;84:1–12.
Young LS, Rickinson A. Epstein–Barr virus: 40 years on. Nat Rev Immunol. 2004;4:757–68. doi:10.1038/nrc1452.
Zandman-Goddard G, Berkun Y, Barzilai O, et al. Exposure to Epstein–Barr virus infection is associated with mild systemic lupus erythematosus disease. Ann N Y Acad Sci. 2009;1173:658–63.
Vial T. Cancers in immunocompromised hosts. J Toxicol Clin Exp. 1992;12:385–95.
Quartuccio L, Baldini C, Bartoloni E, et al. Anti-SSA/SSB-negative Sjögren’s syndrome shows a lower prevalence of lymphoproliferative manifestations, and a lower risk of lymphoma evolution. Autoimmun Rev. 2015;14:1019–22.
Afeltra A, Amoroso A, Garzia P, et al. Systemic lupus erythematosus and multiple myeloma: a rare association. Semin Arthritis Rheum. 1997;26:845–9. doi:10.1016/S0049-0172(97)80029-7.
Bila J, Suvajdzic N, Elezovic I, et al. Systemic lupus erythematosus and IgA multiple myeloma: a rare association? Med Oncol (Totowa, NJ, United States). 2007;24:445–8. doi:10.1007/s12032-007-0047-3.
Vaiopoulos G, Konstantopoulos K, Mantzourani M, et al. Multiple myeloma associated with systemic lupus erythematosus. Leuk Lymphoma. 2003;44:373–4.
Canoso JJ, Cohen AS. Malignancy in a series of 70 patients with systemic lupus erythematosus. Arthritis Rheum. 1974;17:383–90.
Landgren O, Linet MS, McMaster ML, et al. Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study. Int J Cancer. 2006;118:3095–8.
Lipsky PE. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol. 2001;2:764–6. doi:10.1038/ni0901-764.
Rubin L, Urowitz MB, Pruzanski W. Systemic lupus erythematosus with paraproteinemia. Arthritis Rheum. 1984;27:638–44.
Isobe T, Osserman EF. Pathologic conditions associated with plasma cell dyscrasias: a study of 806 cases. Ann N Y Acad Sci. 1971;190:507–18.
Klumb EM, Pinto a C, Jesus GR, et al. Are women with lupus at higher risk of HPV infection? Lupus. 2010;19:1485–91. doi:10.1177/0961203310372952.
Blumenfeld Z, Lorber M, Yoffe N, et al. Systemic lupus erythematosus: predisposition for uterine cervical dysplasia. Lupus. 1994;3:59–61.
Palefsky JM, Minkoff H, Kalish LA, et al. Cervicovaginal human papillomavirus infection in human immunodeficiency virus-1 (HIV)-positive and high-risk HIV-negative women. J Natl Cancer Inst. 1999;91:226–36.
Kane S, Khatibi B, Reddy D. Higher incidence of abnormal pap smears in women with inflammatory bowel disease. Am J Gastroenterol. 2008;103:631–6.
Nyberg G, Eriksson O, Gunnar WN. Increased incidence of cervical atypia in women with systemic lupus erythematosus treated with chemotherapy. Arthritis Rheum. 1981;24:648–50.
Bateman H, Yazici Y, Leff L, et al. Increased cervical dysplasia in intravenous cyclophosphamidetreated patients with SLE: a preliminary study. Lupus. 2000;9:542–4.
Parikh-Patel A, White RH, Allen M, et al. Risk of cancer among rheumatoid arthritis patients in California. Cancer Causes Control. 2009;20:1001–10.
Daling JR, Madeleine MM, Schwartz SM, et al. A population-based study of squamous cell vaginal cancer: HPV and cofactors. Gynecol Oncol. 2002;84:263–70. doi:10.1006/gyno.2001.6502.
Gayed M, Bernatsky S, Ramsey-Goldman R, et al. Lupus and cancer. Lupus. 2009;18:479–85. doi:10.1177/0961203309102556.
Bernatsky SR, Cooper GS, Mill C, et al. Cancer screening in patients with systemic lupus erythematosus. J Rheumatol. 2006;33:45–9.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
The study was approved by the ethical committee of CHS, located at the Soroka Medical Center, Beer-Sheva, Israel.
Additional information
Shir Azrielant and Shmuel Tiosano share equal contribution, and Arnon D. Cohen and Howard Amital share equal contribution.
Rights and permissions
About this article
Cite this article
Azrielant, S., Tiosano, S., Watad, A. et al. Correlation between systemic lupus erythematosus and malignancies: a cross-sectional population-based study. Immunol Res 65, 464–469 (2017). https://doi.org/10.1007/s12026-016-8885-8
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12026-016-8885-8