Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma
Arthritis Research & Therapy 2014, 16:R53 doi:10.1186/ar4486Published: 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 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.