Immunologic Research

, Volume 65, Issue 2, pp 464–469 | Cite as

Correlation between systemic lupus erythematosus and malignancies: a cross-sectional population-based study

  • Shir Azrielant
  • Shmuel Tiosano
  • Abdulla Watad
  • Naim Mahroum
  • Aaron Whitby
  • Doron Comaneshter
  • Arnon D. Cohen
  • Howard Amital
Novel Aspects in Lupus, 2017


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.


Systemic lupus erythematosus Cancer Lymphoma Hodgkin’s disease Smoking Lung cancer 


Compliance with ethical standards

The study was approved by the ethical committee of CHS, located at the Soroka Medical Center, Beer-Sheva, Israel.


  1. 1.
    De Visser KE, Eichten A, Coussens LM. Paradoxical roles of the immune system during cancer development. Nat Rev Cancer. 2006;6:24–37.CrossRefPubMedGoogle Scholar
  2. 2.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    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.CrossRefPubMedGoogle Scholar
  4. 4.
    Askling J, Bongartz T. Malignancy and biologic therapy in rheumatoid arthritis. Curr Opin Rheumatol. 2008;20:334–9.CrossRefPubMedGoogle Scholar
  5. 5.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    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.CrossRefPubMedGoogle Scholar
  7. 7.
    Cibere J, Sibley J, Haga M. Rheumatoid arthritis and the risk of malignancy. Arthritis Rheum. 1997;40:1580–6.CrossRefPubMedGoogle Scholar
  8. 8.
    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.CrossRefPubMedGoogle Scholar
  9. 9.
    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.CrossRefPubMedGoogle Scholar
  10. 10.
    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.CrossRefPubMedGoogle Scholar
  11. 11.
    Gorodetskiy V, Klapper W, Probatova N, et al. Primary diffuse large B-cell lymphoma of the liver in a patient with Sjogren syndrome.Google Scholar
  12. 12.
    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.CrossRefPubMedGoogle Scholar
  13. 13.
    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.CrossRefPubMedGoogle Scholar
  14. 14.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    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.CrossRefGoogle Scholar
  17. 17.
    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.CrossRefPubMedGoogle Scholar
  18. 18.
    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.CrossRefPubMedGoogle Scholar
  19. 19.
    Skaggs BJ, Hahn BH, McMahon M. Accelerated atherosclerosis in patients with SLE—mechanisms and management. Nat Rev Rheumatol. 2012;8:214–23.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Bernatsky S, Boivin JF, Joseph L, et al. An international cohort study of cancer in systemic lupus erythematosus. Arthritis Rheum. 2005;52:1481–90.CrossRefPubMedGoogle Scholar
  21. 21.
    Bernatsky S, Ramsey-Goldman R, Isenberg D, et al. Hodgkin’s lymphoma in systemic lupus erythematosus. Rheumatology. 2007;46:830–2.CrossRefPubMedGoogle Scholar
  22. 22.
    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.CrossRefPubMedGoogle Scholar
  23. 23.
    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.CrossRefGoogle Scholar
  24. 24.
    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.CrossRefGoogle Scholar
  25. 25.
    Cibere J, Sibley J, Haga M. Systemic lupus erythematosus and the risk of malignancy. Lupus. 2001;10:394–400.CrossRefPubMedGoogle Scholar
  26. 26.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    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.CrossRefPubMedGoogle Scholar
  28. 28.
    Guy A, Tiosano S, Comaneshter D, et al. Aortic aneurysm association with SLE—a case–control study. Lupus 2016;0961203316628999.Google Scholar
  29. 29.
    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.
  30. 30.
    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.Google Scholar
  31. 31.
    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.CrossRefPubMedGoogle Scholar
  32. 32.
    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.CrossRefPubMedGoogle Scholar
  33. 33.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Xu Y, Wiernik PH. Systemic lupus erythematosus and B-cell hematologic neoplasm. Lupus. 2001;10:841–50. doi: 10.1191/096120301701548481.CrossRefPubMedGoogle Scholar
  35. 35.
    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.CrossRefPubMedGoogle Scholar
  36. 36.
    Hjalgrim H, Askling J, Rostgaard K, et al. Characteristics of Hodgkin’s lymphoma after infectious mononucleosis. N Engl J Med. 2003;349:1324–32.CrossRefPubMedGoogle Scholar
  37. 37.
    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.CrossRefPubMedGoogle Scholar
  38. 38.
    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.CrossRefPubMedGoogle Scholar
  39. 39.
    Young LS, Rickinson A. Epstein–Barr virus: 40 years on. Nat Rev Immunol. 2004;4:757–68. doi: 10.1038/nrc1452.Google Scholar
  40. 40.
    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.CrossRefPubMedGoogle Scholar
  41. 41.
    Vial T. Cancers in immunocompromised hosts. J Toxicol Clin Exp. 1992;12:385–95.PubMedGoogle Scholar
  42. 42.
    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.CrossRefPubMedGoogle Scholar
  43. 43.
    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.CrossRefPubMedGoogle Scholar
  44. 44.
    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.Google Scholar
  45. 45.
    Vaiopoulos G, Konstantopoulos K, Mantzourani M, et al. Multiple myeloma associated with systemic lupus erythematosus. Leuk Lymphoma. 2003;44:373–4.CrossRefPubMedGoogle Scholar
  46. 46.
    Canoso JJ, Cohen AS. Malignancy in a series of 70 patients with systemic lupus erythematosus. Arthritis Rheum. 1974;17:383–90.CrossRefPubMedGoogle Scholar
  47. 47.
    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.CrossRefPubMedGoogle Scholar
  48. 48.
    Lipsky PE. Systemic lupus erythematosus: an autoimmune disease of B cell hyperactivity. Nat Immunol. 2001;2:764–6. doi: 10.1038/ni0901-764.CrossRefPubMedGoogle Scholar
  49. 49.
    Rubin L, Urowitz MB, Pruzanski W. Systemic lupus erythematosus with paraproteinemia. Arthritis Rheum. 1984;27:638–44.CrossRefPubMedGoogle Scholar
  50. 50.
    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.CrossRefPubMedGoogle Scholar
  51. 51.
    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.CrossRefPubMedGoogle Scholar
  52. 52.
    Blumenfeld Z, Lorber M, Yoffe N, et al. Systemic lupus erythematosus: predisposition for uterine cervical dysplasia. Lupus. 1994;3:59–61.CrossRefPubMedGoogle Scholar
  53. 53.
    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.CrossRefPubMedGoogle Scholar
  54. 54.
    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.CrossRefPubMedGoogle Scholar
  55. 55.
    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.CrossRefPubMedGoogle Scholar
  56. 56.
    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.CrossRefPubMedGoogle Scholar
  57. 57.
    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.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    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.CrossRefPubMedGoogle Scholar
  59. 59.
    Gayed M, Bernatsky S, Ramsey-Goldman R, et al. Lupus and cancer. Lupus. 2009;18:479–85. doi: 10.1177/0961203309102556.CrossRefPubMedGoogle Scholar
  60. 60.
    Bernatsky SR, Cooper GS, Mill C, et al. Cancer screening in patients with systemic lupus erythematosus. J Rheumatol. 2006;33:45–9.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Shir Azrielant
    • 1
    • 2
  • Shmuel Tiosano
    • 1
    • 2
  • Abdulla Watad
    • 1
    • 2
  • Naim Mahroum
    • 1
    • 2
  • Aaron Whitby
    • 1
    • 2
  • Doron Comaneshter
    • 3
  • Arnon D. Cohen
    • 3
    • 4
  • Howard Amital
    • 1
    • 2
  1. 1.Department of Medicine ‘B’, Zabludowicz Center for Autoimmune DiseasesSheba Medical CenterTel-HashomerIsrael
  2. 2.Sackler Faculty of MedicineTel-Aviv UniversityTel-AvivIsrael
  3. 3.Chief Physician’s OfficeClalit Health ServicesTel-AvivIsrael
  4. 4.Siaal Research Center for Family Medicine and Primary Care, Faculty of Health SciencesBen-Gurion University of the NegevBeer-ShevaIsrael

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