Short communicationCancer risk in systemic lupus: An updated international multi-centre cohort study
Highlights
► We studied 16,409 SLE patients, finding a slight increase in over-all cancer risk versus the general population. ► For non-Hodgkin's lymphoma, NHL the SIR was 4.39. 95% CI 3.46, 5.49). ► However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61–0.88) and endometrial (SIR 0.44, 95% CI 0.23–0.77) cancer.
Introduction
Systemic lupus erythematosus (SLE) is one of the most common systemic autoimmune rheumatic diseases, often affecting young and middle-aged people. Females are particularly affected (female:male ratio of 9:1). Although survival in SLE has improved, morbidity related to the disease and its treatment remains considerable. One important consideration is cancer risk.
The immune system's role in cancer risk is a topic of increasing interest, and accordingly, the association between autoimmunity and cancer has been under study for over a decade [1]. Suggested pathways linking SLE and cancer include possible links with medication exposures, or even interactions between medications and viral exposures. Also potentially pertinent are clinical characteristics, such as co-existing Sjogren's syndrome or other overlap syndromes that may occur in SLE [2]. Some have hypothesized that an increased prevalence of traditional “lifestyle” cancer risk factors may influence malignancy incidence in SLE [3]. Additionally, inherent immune system abnormalities have been suggested as mediators of a potentially increased cancer risk in SLE [4].
To date, varying estimates of cancer risk in SLE have been generated, most with fairly wide confidence intervals (CIs). The standardized incidence ratio (SIR) estimates for over-all cancer in these studies ranged from 1.1 (95% CI 0.7–1.6) [5] to 2.6 (95% CI 1.5–4.4) [6]. These studies do not represent optimal estimates of cancer risk in SLE, due to small sample sizes and possibly non-representative sampling. In 2005 we published a large multi-centre study (23 centres, 9547 SLE patients) that clarified cancer risk in SLE, particularly with respect to a nearly 4 fold increase of non-Hodgkin lymphoma (NHL) [7]. Our current goal was to conduct in-depth, updated analyses of cancer risk in SLE, compared to the general population.
Section snippets
Materials and methods
We assembled a multisite (30 centers) international cohort of patients diagnosed with SLE. These consisted of clinically confirmed SLE patients in follow-up, the vast majority of who fulfill American College of Rheumatology (ACR) criteria (one cohort, in Scotland, was assembled using administrative data). Patients were linked to regional tumor registries to determine cancer occurrence. Information was available on birth-date, sex, lupus diagnosis and cohort entry dates, and date of death, if
Results
In total 16,409 patients were studied (Table 1); 7700 of these originated from the United States, 3689 from Canada, 4250 from Europe and 770 from Asia (Korea). Ninety percent were female. The patients provided a total of 121,283 person–years of follow-up (mean 7.4 years) spanning the calendar period 1958–2009, although most of the person–years came from the 1970's onward.
Within the observation interval, 644 cancers occurred (Table 2). The data confirmed an increased risk of cancer among
Discussion
Our study results more precisely define cancer risk in SLE versus the general population, highlighting a dichotomy. On one hand, there is an increased risk of NHL, leukemia and cancers of the vulva, lung, thyroid, and possibly liver. Conversely, there is a decreased risk of breast, endometrial, and possibly ovarian cancer. Hence, the over-all cancer risk in SLE is only slightly increased, compared to the general population.
This is in fact quite similar to the profile seen in another autoimmune
Conclusion
To summarize, our data support an association between SLE and cancer, highlighting the risk for NHL and leukemia, but also demonstrating an increased risk of vulvar, lung, thyroid, and possibly liver cancers. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. On the other hand, women with SLE appear to have a decreased risk of breast, endometrial, and possibly ovarian cancer. The etiology of this phenomenon is also uncertain, though
Potential conflicts of interest
None.
Grant support
This research was funded by Canadian Institutes of Health Research/Arthritis Society grant RG06/092 and National Institutes of Health (NIH) grant 1R03CA128052-01. We also acknowledge the grant that supports the Chicago Lupus Database, NIH/NIAMS P60 2 AR30692 and the grants that support the UCSF Lupus Outcomes Study, NIH/NIAMS P60 AR053308 and NIH/NIAMS R01 5R01AR56476-9, the grant that support the Hopkins Lupus Cohort NIH R01 AR43727, and the grant by the Department of Education, Universities
Acknowledgments
We acknowledge the assistance of Jennifer Lee, Elizabeth Turnbull and Autumn Neville. Our efforts were made possible through the endorsement and support of the Systemic Lupus International Collaborating Clinics research network. Dr. Criswell would like to acknowledge support from the Alliance for Lupus Research and from a Kirkland Scholar Award.
References (35)
- et al.
Lung cancer in systemic lupus erythematosus
Lung Cancer
(2007) - et al.
Prevalence of thyroid dysfunctions in systemic lupus erythematosus
Metabolism
(2010) - et al.
Autoimmune thyroid disease: a risk factor for thyroid cancer
Endocr Pract
(2011) - et al.
The risk of lymphoma development in autoimmune diseases: a meta-analysis
Arch Intern Med
(2005) - et al.
Increased risk of lymphoma in sicca syndrome
Ann Intern Med
(1978) - et al.
The prevalence of factors influencing cancer risk in lupus: social habits reproductive issues and obesity
J Rheumatol
(2002) - et al.
Expression of APRIL in diffuse large B cell lymphomas from patients with systemic lupus erythematosus and rheumatoid arthritis
J Rheumatol
(2011) - et al.
Malignancy in systemic lupus erythematosus
Arthritis Rheum
(1996) - et al.
Increased risk of cancer in patients with systemic lupus erythematosus
Ann Rheum Dis
(1992) - et al.
An international cohort study of cancer in systemic lupus erythematosus
Arthritis Rheum
(2005)
A meta-analysis of the incidence of malignancy in adult patients with rheumatoid arthritis
Arthritis Res Ther
Molecular pathogenesis of follicular lymphoma
Haematologica
Clinical, immunologic, and molecular factors predicting lymphoma development in Sjogren's syndrome patients
Clin Rev Allergy Immunol
Susceptibility of patients with rheumatic diseases to B-cell non-Hodgkin lymphoma
Nat Rev Rheumatol
Non-Hodgkin's lymphoma in systemic lupus erythematosus
Ann Rheum Dis
Histology, prognostic factors, treatment, and outcome in SLE patients with non-Hodgkins lymphoma [Abstract]
Arthritis Rheum
The relationship between cancer and medication exposures in systemic lupus erythematosus: a case-cohort study
Ann Rheum Dis
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