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Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma

Pia Moinzadeh12, Carmen Fonseca1, Martin Hellmich3, Ami A Shah4, Cecilia Chighizola15, Christopher P Denton1* and Voon H Ong1

Author Affiliations

1 Centre for Rheumatology and Connective Tissue Diseases, University College London (UCL) Medical School, Royal Free Hospital, Pond Street, London NW3 2QG, UK

2 Department of Dermatology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany

3 Institute of Medical Statistics, Informatics and Epidemiology, University of Cologne, Kerpener Str. 62, 50924 Cologne, Germany

4 Division of Rheumatology, Johns Hopkins University School of Medicine, Johns Hopkins Scleroderma Center, 5501 Hopkins Bayview Circle, Room 1B.32, Baltimore, MD 21224, USA

5 Rheumatology Division, Department of Clinical Sciences and Community Health, University of Milan, Istituto G. Pini Piazza C. Ferrari, 1 – 20122 Milan, Italy

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Arthritis Research & Therapy 2014, 16:R53  doi:10.1186/ar4486

Published: 14 February 2014



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 SSc onset and cancer diagnosis.


We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by 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 relevant to the risk for development of cancer in SSc patients.


Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (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 those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 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 a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).


Our study independently confirms, in what is to the best of our knowledge 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 cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.