7Malignancy in systemic lupus erythematosus: what have we learned?
Section snippets
Cancer risk in SLE relative to that in the general population
For some time there was significant debate as to whether persons with SLE did in fact have an increased risk of cancer compared to the general population. Of particular concern were haematological malignancies (particularly lymphoma) and lung cancer, two types of cancer that have been demonstrated to be elevated in other autoimmune rheumatic diseases such as rheumatoid arthritis (RA) [2].
In the past decade, several large studies have defined the magnitude of the cancer risk in SLE. A Swedish
More on lupus and haematological cancer risk
Evidence for an association between SLE and NHL was also suggested by Smedby et al in a population-based case–control study. Here, the frequency of autoimmune diseases among NHL patients from the general population was assessed and compared with matched population-based cancer-free controls [11]. Over 3000 NHL cases were studied, and of these, eight had a prior history of SLE, whereas only two of the matched cancer-free controls reported a history of SLE. The adjusted odds ratio (OR) for SLE
Characteristics of lung cancer risk in SLE
The multicentre international lupus cohort study demonstrated that SLE patients are at higher risk than the general population for lung cancer (SIR 1.37; 95% CI 1.05, 1.76). A review of the reported histology of the lung cancers from this study showed that the majority were adenocarcinoma, as is seen in the general population [22].
One study of lung cancers arising in various autoimmune rheumatic diseases (primarily systemic sclerosis, RA, and SLE) suggested that, on average, such malignancies
Is cancer risk in SLE driven by medication exposures?
Unfortunately, the most clinically relevant question, the mechanism underlying the association between cancer and SLE, remains largely unanswered. A potential link between cancer risk and drug exposures in SLE remains difficult to establish definitively because of the close association between lupus disease activity and use of immunosuppressives. Of note, it has been shown by several authors that the increased risk of lymphoma in SLE seems to be highest (relative to general population cancer
Haematological malignancies and inflammation
General support for the role of chronic autoimmunity and immune stimulation in haematological malignancy risk was suggested by several administrative database studies which found increased risk (compared to that in the general population) for patients with a diverse group of autoimmune conditions *[37], *[38]. One caveat of their methodology was the construction of study samples using hospitalization data, as it is well known that hospitalized people are more likely to be diagnosed with
Cervical dysplasia in women with SLE
The issue of cervical dysplasia remains of considerable importance in SLE. A group of SLE patients with normal cytology tests at baseline was followed to determine the incidence of cervical intraepithelial neoplasia (CIN) [45]. The 3-year incidence was 9.8%, significantly higher than figures for the general population. Interestingly, there were no new cases of CIN among SLE subjects exposed only to prednisone or azathioprine; in contrast, in subjects exposed to cyclophosphamide, the incidence
Summary
So far, we know that there is a slight increased risk in SLE for all cancers combined compared to that in the general population. However, this is largely driven by an increased risk for haematological malignancies, particularly NHL. Hodgkin's lymphoma may be increased as well. There is a moderately increased risk of lung cancer, and some evidence for increased risk of rarer cancer types, such as hepatobiliarly cancer and vulvar/vaginal malignancies.
There is also very good evidence that
References (49)
- et al.
Rheumatoid arthritis and cancer risk
Eur J Cancer
(1996 Sep) - et al.
An analysis of Berkson's bias in case-control studies
J Chronic Dis
(1986) - et al.
Lung cancer in systemic lupus erythematosus
Lung Cancer
(2007 Jun) - et al.
Clinical features of lung cancer in patients with connective tissue diseases: a 10-year hospital based study
Respir Med
(2008 Apr) - et al.
Autoimmune diseases, asthma and risk of haematological malignancies: a nationwide case-control study in Sweden
Eur J Cancer
(2006 Nov) - et al.
Genetic variation in TNF and IL10 and risk of non-Hodgkin lymphoma: a report from the InterLymph Consortium
Lancet Oncol
(2006 Jan) - et al.
Cell-mediated immunity in rheumatic disease
Hum Pathol
(1986 Mar) - et al.
The risk of lymphoma development in autoimmune diseases: a meta-analysis
Arch Intern Med
(2005 Nov 14) - et al.
Increased cancer incidence in a Swedish cohort of patients with systemic lupus erythematosus
Scand J Rheumatol
(2002) - et al.
An international cohort study of cancer in systemic lupus erythematosus
Arthritis Rheum
(2005)
Hormonal and reproductive risk factors for development of systemic lupus erythematosus: results of a population-based, case-control study
Arthritis Rheum
Cancer risk in a cohort of patients with systemic lupus erythematosus (SLE) in California
Cancer Causes Control
Race/ethnicity and cancer occurrence in systemic lupus erythematosus
Arthritis Rheum
Increased risk of malignancy in patients with systemic lupus erythematosus
J Investig Med
Mortality in systemic lupus erythematosus
Arthritis Rheum
Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype
J Natl Cancer Inst
Lymphoma subtypes and prognosis in patients with systemic lupus erythematosus
Arthritis Rheum
Non-Hodgkin's lymphoma in systemic lupus erythematosus
Ann Rheum Dis
A closer look at non-Hodgkin's lymphoma cases in a national Swedish systemic lupus erythematosus cohort: a nested case-control study
Ann Rheum Dis
Malignant lymphoma in patients with systemic rheumatic disease (rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, and dermatomyositis): a clinicopathologic study of 24 Japanese cases
Int J Surg Pathol
Autoimmunity and susceptibility to Hodgkin lymphoma: a population-based case-control study in Scandinavia
J Natl Cancer Inst
Hodgkin's lymphoma in systemic lupus erythematosus
Rheumatology (Oxford)
Familial characteristics of autoimmune and hematologic disorders in 8,406 multiple myeloma patients: a population-based case-control study
Int J Cancer
Risk of multiple myeloma following medication use and medical conditions: a case-control study in Connecticut women
Cancer Epidemiol Biomarkers Prev
Cited by (54)
Oral immune-mediated disorders with malignant potential/association: An overview
2023, Disease-a-MonthCitation Excerpt :As cytotoxic or immunosuppressive drugs (such as azathioprine and cyclophosphamide) are prescribed for the management of systemic lupus, the occurrence of malignancy due to these agents has also been reported.79–84 One group of researchers have also reported that the potential protective effect of the antimalarial drugs may also increase the probability of malignancy.85,86 Some shreds of evidence reveals the presence of a few other traditional factors that could be related to the increased probability of cancer development in lupus patients, and these include obesity, reproductive issues (such as low parity or nulliparity, decreased use of oral contraceptives) and smoking.61,87–92
Investigation of the relationship of Epstein-Barr virus with in situ hybridization in renal-cell carcinomas
2018, Annals of Diagnostic PathologyCitation Excerpt :However, the details of this relationship are not well understood. Many medications may be used during treatment, which may also lead to chronic inflammation [27-28]. In a large study involving 6438 patients, EBV was detected through in situ hybridization in two of 15 patients followed for SLE and who were subsequently diagnoses with NHL [29].
Ro60/SSA levels are increased and promote the progression of pancreatic ductal adenocarcinoma
2018, Biochemical and Biophysical Research CommunicationsCitation Excerpt :To identity of the function of Ro60/SSA and its relevance to autoimmune and other diseases is unclear [21]. The association between malignant diseases and systemic autoimmune chronic inflammatory conditions has been outlined over previous decades [6,22]. Bockle et al. proposed that Ro/SSA antibody-positive patients have a greater likelihood of developing cancer in general, but especially melanoma and lymphoma [6].
Musculoskeletal Syndromes in Malignancy
2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth EditionA literature-driven method to calculate similarities among diseases
2015, Computer Methods and Programs in BiomedicineTreatment of systemic lupus erythematosus: Myths, certainties and doubts
2013, Medicina Clinica