Exploring the Links Between Systemic Lupus Erythematosus and Cancer
Section snippets
Review of cancer risk in systemic lupus erythematosus
Efforts to estimate cancer risk in SLE have most often been done with clinical cohorts [6], [7], [8], [9], [10], [11], [12], [13], where subjects have a definite diagnosis of SLE, either by American College of Rheumatology (ACR) criteria [15] or by clinical judgment. As SLE is a rare condition [16], the sizes of these cohorts have been relatively small, ranging from 116 [13] to 724 [12]. Alternatively, attempts [5], [17] have been made to generate much larger national cohorts, through
Is surveillance bias a concern?
There are strong reasons to believe that surveillance bias does not entirely explain the findings of an increased risk of malignancy in SLE. Breast cancer, a neoplasm amenable to screening, is not consistently increased in SLE cohort studies, in contrast to the striking increase in hematologic cancers, where there is no formal screening strategy for early detection. Bias could still operate in that cancers may be uncovered sooner in a lupus patient (during a periodic clinic visit) than in the
Etiology of cancer risk in systemic lupus erythematosus
Because the association between malignancy and SLE seems to be substantiated, what are the pathogenic pathways linking SLE and cancer? Possibilities include an increased prevalence of traditional lifestyle risk factors influencing cancer incidence, putative links between medication use and cancer in SLE, or potential interactions between medications and viral exposures. Also of interest are clinical characteristics, such as secondary Sjogren's or other overlap syndromes; geographic and race or
Lifestyle cancer risk factors in systemic lupus erythematosus: smoking and obesity
Important lifestyle factors associated with cancer development in the general population include smoking and obesity. Tobacco use, particularly cigarette smoking, is an important cause of lung and other cancers [40]. The prevalence of smoking in SLE has been estimated in several cohorts [41], [42], [43], [44], [45], but comparable figures for the population have often not been presented. Several small studies [6], [45], [46] have suggested that the proportion of smokers in SLE is similar to
Medications and cancer in systemic lupus erythematosus
Although there are several case reports of malignancies associated with either azathioprine [53], [54] or cyclophosphamide [55], [56], [57] in SLE, the striking association of azathioprine with lymphoreticular malignancies in the NZB/NZW mouse model of SLE [58] and in organ transplant recipients [59], [60] (where cyclosporin also seems culpable) has not been clearly demonstrated in human populations with SLE [61]. There is also no convincing evidence that cancer occurrence is a common outcome
Potential interactions between medications and viral exposures
As well as potentially relevant exposures of immunosuppressive agents, one might also invoke viral exposures [77], [78], [79], [80] or an interaction between immunosuppressive agents and viral exposures. It is possible that infectious exposures, particularly viruses such as the Epstein-Barr virus (EBV), may both trigger SLE [81] and create a predisposition to malignancy [82]. Although this hypothesis is intriguing, EBV infection is not likely to entirely explain the increased risk of cancer in
Possible clinical characteristics important in systemic lupus erythematosus–related malignancy
One factor that has been postulated as a potential mediator of cancer incidence in patients who have SLE is the secondary occurrence of Sjögren's syndrome. Because of the striking association between primary Sjögren's and NHL [87], it has been proposed that secondary Sjögren's may explain some of the increased cancer risk in SLE [88], [89] However, the few studies assessing the relationship between secondary Sjögren's syndrome in SLE and cancer have not definitively established this link. The
Geographic variations and race/ethnicity in cancer risk
There are, of course, important worldwide variations [96] in the baseline population cancer rates that are, in part, dependent not just on the country where one lives, but also on the racial or ethnic mix (as different race or ethnic groups have different baseline cancer risk [40], [96], [97], [98]). There has been some preliminary work within the multicenter SLE cohort established by members of SLICC and CaNIOS with respect to the effect of geographic factors and race/ethnicity on cancer
Genetic factors and their place in the pathways between autoimmunity and non-Hodgkin's lymphoma
The genetic abnormalities that may underlie the association between SLE and NHL are unknown. An important feature of NHL is the presence of chromosomal abnormalities (Table 2), such as translocations where an oncogene is juxtaposed next to a gene important in immune cell function [104]. These chromosomal abnormalities are of interest in terms of being possible common pathways linking SLE and lymphoproliferative malignancies.
Recommendations for cancer screening
With respect to what recommendations can be made to clinicians for suggested cancer screening of patients who have SLE, there is no evidence that any formal strategies be used, aside from following age and specific recommendations for the general population [105]. Caveats to this include the following suggestions for patients exposed to immunosuppressive agents: (1) specific screening for cyclophosphamide-related bladder cancer and (2) recommendations for the frequency of pap testing in any
Summary
Recent data confirm that certain cancers, particularly hematologic, occur more frequently in SLE than in the general population. Numerous pathogenic mechanisms are possible, but hypotheses remain largely speculative. In particular, data are inadequate on how cancer risk in SLE may be related to medication exposures. To evaluate the impact of medication exposures on cancer risk in SLE, cooperative efforts of SLICC and CaNIOS are currently in progress. This should provide much-needed insight into
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Cited by (23)
Myeloid disorders after autoimmune disease
2019, Best Practice and Research: Clinical HaematologyCitation Excerpt :In addition to their elevated incidence risk in SLE, hematologic cancer-related mortality is significantly higher in SLE when compared to the general population [87,88]. It remains to be clarified whether the poorer prognosis in SLE-related hematologic malignancies is related to a more aggressive biology, decreased survival related to associated SLE, or due to other factors [89]. Several case reports and case series have reported the association between SLE and AML with a few suggesting a link to prior cytotoxic/immunosuppressive drug exposure [68,90–97].
Musculoskeletal Syndromes in Malignancy
2016, Kelley and Firestein's Textbook of Rheumatology: Volumes 1-2, Tenth EditionIncidence of Cancer in a Cohort of Spanish Patients With Systemic Lupus Erythematosus
2013, Reumatologia ClinicaCitation Excerpt :As Zintzaras et al. point out in their meta-analysis,27 the SIR has become lower over the years (in 1992 it was 44.40, in 1995 it was 27.10, and in 2001 it was 7.42), which would explain why our series, despite being an open observational study from 1992, found no lymphomas. Secondly, non-Hodgkin's lymphoma is usually more common in men28 and only 10% of our cohort was male. The third reason for the lack of association between SLE and haematological tumours relates to the association between lymphoma and inflammation.
Musculoskeletal Syndromes in Malignancy
2012, Kelley's Textbook of Rheumatology: Volume 1-2, Ninth EditionClinical approach to lupus nephritis: Recent advances
2009, European Journal of Internal MedicineCitation Excerpt :Long term follow-up studies have demonstrated that, with treatment, patient survival is 72% at 10 years and 61% at 20 years; this compares with 5-year survival rates of 17% of patients with class IV disease in the 1950s [4]. Nowadays the major causes of death in patient with SLE are infections [5], atherosclerosis [6] and neoplasia [7]. Most patients with SLE do not present renal involvement; only 25% of them have this as presenting feature initially, additionally in 5% of cases, usually men older than 40 years, renal involvement can be present several years before SLE diagnosis [8].
Long-Term Prognosis and Causes of Death in Systemic Lupus Erythematosus
2006, American Journal of Medicine
The authors would like to acknowledge the following grant support: (S.B.) Canadian Institutes of Health Research (CIHR)/Lupus Canada Fellowship, Canadian Arthritis Network Fellowship, and Lupus Manitoba; R.R.-G) Arthritis Foundation, Clinical Science Grant, Arthritis Foundation Greater Chicago Chapter National Institutes of Health Grants AR 02138 and AR 48098, and Lupus Foundation of Illinois Chapter Grant; and (A.C.) National Cancer Institute of Canada grants CIHR 013135 and 10005, TAS 99105, Singer Family Fund for Lupus Research, and CIHR Investigator Award.