Systemic sclerosis (scleroderma) and cancer risk: systematic review and meta-analysis of observational studies.
ABSTRACT Objectives. A higher incidence of cancer in scleroderma patients compared with the general population has been suggested by several observational studies, reporting, however, different estimates. Therefore, we aimed to perform a systematic review and meta-analysis to definitely assess this association.Methods. We searched MEDLINE and Embase for all original articles of observational studies on cancer incidence in scleroderma patients without language restriction published up to December 2011. Two independent authors reviewed all titles/abstracts and retrieved detailed full-text of potentially relevant articles to identify studies according to predefined selection criteria. Summary estimates were derived using random-effects model and reported as relative risk (RR). Publication bias was evaluated by trim and fill analysis.Results. From articles initially identified, 16 original studies, involving more than 7000 patients, were included in the present review. Compared with the general population, the summary RR to develop all invasive cancers in scleroderma patients was 1.75 (95% CI 1.41, 2.18). The results for selected cancer sites indicated a strong association with lung cancer (RR 4.35; 95% CI 2.08, 9.09), and a significant increased risk also for haematological neoplasms (RR 2.24; 95% CI 1.53, 3.29). The relation with breast cancer, suggested in some previous epidemiological studies, was not confirmed (RR 1.05; 95% CI 0.86, 1.29).Conclusion. The present meta-analysis, the first on scleroderma and cancer risk, provides definite estimates on the association between scleroderma and cancer.
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ABSTRACT: IntroductionRheumatic diseases (RDs) are associated with different cancers; however, it is unclear whether particular cancers are more prevalent in certain RDs. Here, we examined the relative incidence of several cancers in a single homogenous cohort of patients with different RDs.Methods Patients (n¿=¿3,586) diagnosed with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), dermatomyositis (DM), or polymyositis were included. Cancer diagnosis was based on histopathology. The 2008 Korean National Cancer Registry served as the reference for calculating standardized incidence ratios (SIRs).ResultsDuring the follow-up period of 31,064 person-years (PYs), 187 patients developed cancer. RA and SLE patients showed an increased risk of non-Hodgkin¿s lymphoma (SIR, 3.387; 95% CI, 1.462 to 6.673, SIR, 7.408; 95% CI, 2.405 to 17.287, respectively). SLE patients also had a higher risk of cervical cancer (SIR, 4.282; 95% CI, 1.722 to 8.824). SSc patients showed a higher risk of lung cancer (SIR, 4.17; 95% CI, 1.977 to 10.131). Endometrial cancer was increased only in patients with DM (SIR, 30.529; 95% CI, 3.697 to 110.283). RA patients had a lower risk for gastric cancer (SIR, 0.663; 95% CI, 0.327 to 0.998). The mean time between the RD and cancer diagnosis ranged from 0.1 to 16.6 years with the shortest time observed in patients with DM (2.0¿±¿2.1 years).Conclusions Different RDs are associated with particular cancers. Thus, cancer surveillance tailored to specific RD might be beneficial.Arthritis Research & Therapy 08/2014; 16(5):428. · 4.12 Impact Factor
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ABSTRACT: Systemic sclerosis (SSc) is an autoimmune disease characterized by extensive visceral organ and skin fibrosis. SSc patients have increased production of autoreactive antibodies and Wnt signaling activity. We found that expression of the gene encoding Wnt inhibitor factor 1 (WIF-1) was decreased in fibroblasts from SSc patient biopsies. WIF-1 deficiency in SSc patient cells correlated with increased abundance of the Wnt effector β-catenin and the production of collagen. Knocking down WIF-1 in normal fibroblasts increased Wnt signaling and collagen production. WIF-1 loss and DNA damage were induced in normal fibroblasts by either SSc patient immunoglobulins or oxidative DNA-damaging agents, such as ultraviolet light, hydrogen peroxide, or bleomycin. The DNA damage checkpoint kinase ataxia telangiectasia mutated (ATM) mediated WIF-1 silencing through the phosphorylation of the transcription factor c-Jun, which in turn activated the expression of the gene encoding activating transcription factor 3 (ATF3). ATF3 and c-Jun were recruited together with histone deacetylase 3 (HDAC3) to the WIF-1 promoter and inhibited WIF-1 expression. Preventing the accumulation of reactive oxygen species or inhibiting the activation of ATM, c-Jun, or HDACs restored WIF-1 expression in cultured SSc patient cells. Trichostatin A, an HDAC inhibitor, prevented WIF-1 loss, β-catenin induction, and collagen accumulation in an experimental fibrosis model. Our findings suggest that oxidative DNA damage induced by SSc autoreactive antibodies enables Wnt activation that contributes to fibrosis.Science Signaling 09/2014; · 7.65 Impact Factor
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ABSTRACT: In rare cases, tumors are associated with secondary Raynaud's phenomenon in systemic sclerosis (SSc). We report the case of a patient presenting cutaneous limited SSc associated with CD30 anaplastic lymphoma with cutaneous and lymph node involvement in whom the capillaroscopic scleroderma pattern regressed completely after autologous bone marrow transplantation, with complete remission of the lymphoma.Annales de Dermatologie et de Vénéréologie 06/2014; 141(6-7):446-451. · 0.67 Impact Factor