Cancer risk in systemic lupus: An updated international multi-centre cohort study

Abstract

OBJECTIVE To update estimates of cancer risk in SLE relative to the general population. METHODS A multisite international SLE cohort was linked with regional tumor registries. Standardized incidence ratios (SIRs) were calculated as the ratio of observed to expected cancers. RESULTS Across 30 centres, 16,409 patients were observed for 121,283 (average 7.4) person-years. In total, 644 cancers occurred. Some cancers, notably hematologic malignancies, were substantially increased (SIR 3.02, 95% confidence interval, CI, 2.48, 3.63), particularly non-Hodgkin’s lymphoma, NHL (SIR 4.39, 95% CI 3.46, 5.49) and leukemia. In addition, increased risks of cancer of the vulva (SIR 3.78, 95% CI 1.52, 7.78), lung (SIR 1.30, 95% CI 1.04, 1.60), thyroid (SIR 1.76, 95% CI 1.13, 2.61) and possibly liver (SIR 1.87, 95% CI 0.97, 3.27) were suggested. However, a decreased risk was estimated for breast (SIR 0.73, 95% CI 0.61–0.88), endometrial (SIR 0.44, 95% CI 0.23–0.77), and possibly ovarian cancers (0.64, 95% CI 0.34–1.10). The variability of comparative rates across different cancers meant that only a small increased risk was estimated across all cancers (SIR 1.14, 95% CI 1.05, 1.23). CONCLUSION These data estimate only a small increased risk in SLE (versus the general population) for cancer over-all. However, there is clearly an increased risk of NHL, and cancers of the vulva, lung, thyroid, and possibly liver. It remains unclear to what extent the association with NHL is mediated by innate versus exogenous factors. Similarly, the etiology of the decreased breast, endometrial, and possibly ovarian cancer risk is uncertain, though investigations are ongoing.

Pregnancy and menopause in patients with Systemic Lupus Erythematosus and/or Antiphospholipid Syndrome: practical guide from EULAR

“…[73][74][75] A relationship between cervical abnormalities and previous use of immunosuppressive drugs, particularly those exposed to cyclophosphamide in a cumulative dose-dependent way, has been reported. 76,77 Thus, a preventive counseling about cancer surveillance appears relevant in sexually active patients with SLE who receive immunosuppressive therapy, and gynecologic visits at shorter intervals than in general population seem to be a reasonable approach in these patients.…”

Acceleration of tumor growth due to dysfunction in M1 macrophages and enhanced angiogenesis in an animal model of autoimmune disease

“…[17][18][19][20] In addition, a meta-analysis demonstrated an increased risk of malignant lymphoma and lung cancer in patients with RA. 25 There are several possible explanations for the link between lymphoma and autoimmune diseases.…”

“…In addition, recent studies of the relationship between autoimmunity and tumor immunity demonstrate that the incidence rate of some malignant tumors, such as hematological tumors, lung cancer, and thyroid cancer, is epidemiologically higher in the patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) than that in healthy controls. [17][18][19][20] However, the precise relationship between autoimmunity and tumor immunity remains unclear.…”

Structural insights into protein-protein interactions governing regulation in transcription initiation and ubiquitination

“…Furthermore, TRIM21 regulates the activity of many transcription factors that are directly related to cytokine production and oncogenic or tumor suppressor proteins, a function, which could provide a molecular connection between autoimmune diseases, inflammation and cancer. Increased risk of lymphomas in SLE patients has been widely noted 163 , and patients with SS have been found to have a higher prevalence of non-Hodgkin's lymphomas, possibly due to antigenic simulation in lymphocytes by autoantigens 164 . Although experimental studies support the notion of TRIM21-substrate interaction through its PRY-SPRY domain, many molecular questions remain to be answered.…”