Istituto di Ricerche Farmacologiche 'Mario Negri', Via Giuseppe La Masa 19, Milan, Dipartimento di Scienze Cliniche e Molecolari, Istituto di Clinica Medica, Università Politecnica delle Marche, Via Tronto 10/A, Ancona, Dipartimento di Medicina del Lavoro, Università degli Studi di Milano, Via Vanzetti 4, Milan, Clinica Medica, Dipartimento di Medicina Interna e Specialistica, Ospedali Riuniti, Via Conca 71, Ancona and Dipartimento di Biologia e Patologia Cellulare e Molecolare, Università 'Federico II', Via S. Pansini 5, Naples, Italy.
Background Systemic sclerosis (Scleroderma) is a rare, immune-mediated, complex disorder characterized by extensive fibrosis and vascular alterations. A higher incidence of cancer - especially lung, breast and hematological cancer- in scleroderma patients compared to the general population has been suggested by several observational studies, reporting, however, different estimates.
Objectives The present study performed a systematic review and meta-analysis to definitely assess this relevant issue.
Methods We searched Medline for all original articles of observational studies on cancer incidence in scleroderma patients without language restriction published up to December 2010. 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 1102 articles initially identified, 15 original studies, involving more than 5000 patients, were included in the present review. Compared to the general population, the summary RR to develop all invasive cancers in scleroderma patients was 1.81 (95% CI, 1.40-2.34). The results for selected cancer sites indicated a strong association with lung cancer (RR 4.4; 95% CI, 1.86-10.31), and a significant increased risk also for haematological neoplasms (RRs 2.1; 95%, CI 1.35-3.14). The relation with breast cancer, suggested in some previous epidemiological studies, was not confirmed (RRs 1.01; 95% CI, 0.81-1.26).
Conclusions The present meta-analysis, the first on scleroderma and cancer risk, provides definite evidence of a significant association between scleroderma and cancer.
Disclosure of Interest None Declared
"The magnitude of absolute risk for these individual cancers is likely to be low
[32,38,39]. For example, the recent meta-analysis reported by Bonifazi et al.
 included a large number of patients from a heterogeneous cohort and case–control retrospective studies, and the authors did not find an increased risk of breast cancers, although the results of some other studies have implicated a strong temporal clustering of breast cancer with SSc onset
[Show abstract][Hide abstract] ABSTRACT: We assessed the profile and frequency of malignancy subtypes in a large single centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between onset of SSc and cancer diagnosis.
A retrospective study of a well-characterised cohort of SSc cases attending a large tertiary referral centre was undertaken with clinical data collected through our clinical database and review of patient records. We evaluated development of all cancers in this cohort and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details including antibody reactivities were explored to find associations for development of cancer in SSc.
Among 2177 patients with SSc, 7.1% of patients had a history of cancer. 26% were positive for anti-centromere antibodies (ACA), 18.2% were positive for anti-Scl70 antibodies and 26.6% were positive for anti-RNA polymerase III antibody (RNAP). The major malignancy subtypes were breast cancer (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological cancers (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased than those with anti-Scl70 (6.3%) and ACA (6.8%) (p < 0.0001 and p < 0.001 respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than other autoantibody specificities (ACA 23.5%; p < 0.008 and anti-Scl70 antibodies 13.6%, p < 0.002 respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP and SSc patients with anti-RNAP had two-fold increased hazard ratio for cancers compared to patients with ACA (p < 0.0001).
Our study confirmed independently, in the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of suspicion should be cautiously maintained in these cases and investigations for underlying malignancy should be considered where clinically appropriate.
"To interpret these findings correctly, it is necessary to determine the underlying risk of cancer development in SSc patients compared to the general population. The only systematic review of malignancy risk in SSc  was limited in its search scope. It calculated the overall relative risk of malignancy in SSc based on mixed prevalence and incidence ratios and summarized the results on malignancy risk in SSc patients and SSc risk in patients with certain types of cancer, creating a potential bias. "
[Show abstract][Hide abstract] ABSTRACT: The link between systemic disease and cancer is not fortuitous. An autoimmune disease can represent the starter for developing a non-Hodgkin lymphoma. This is particularly true for Sjögren's syndrome that is associated with the highest risk of lymphoma (odds ratio up to 44). Other systemic autoimmune diseases concerned are systemic lupus with an odds ratio of 4.5 and rheumatoid arthritis with an odds ratio of 2 to 3. It is now well established that high inflammatory activity, rather than immunosuppressive treatment, is the major risk determinant. The association between solid cancer and autoimmune systemic disease is uncommon and concerns in particular scleroderma and lung cancer. Concerning biotherapy-induced cancers, there is no demonstrated increased risk with anti-TNFα (except for cutaneous carcinoma and maybe melanoma) or with tocilizumab and abatacept even if studies with longer follow-up are needed at least for these two last drugs.
La Revue de Médecine Interne 11/2013; · 1.07 Impact Factor
Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.