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

Pia Moinzadeh, Carmen Fonseca, Martin Hellmich, Ami Shah, Cecilia Chighizola, Christopher P. Denton, Voon H. Ong

Research output: Contribution to journalArticle

Abstract

Introduction: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.Methods: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.Results: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).Conclusions: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.

Original languageEnglish (US)
Article numberR53
JournalArthritis Research and Therapy
Volume16
Issue number1
DOIs
StatePublished - Feb 14 2014

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RNA Polymerase III
Autoantibodies
Neoplasms
Antibodies
Systemic Scleroderma

ASJC Scopus subject areas

  • Rheumatology
  • Immunology
  • Immunology and Allergy
  • Medicine(all)

Cite this

Moinzadeh, P., Fonseca, C., Hellmich, M., Shah, A., Chighizola, C., Denton, C. P., & Ong, V. H. (2014). Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. Arthritis Research and Therapy, 16(1), [R53]. https://doi.org/10.1186/ar4486

Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. / Moinzadeh, Pia; Fonseca, Carmen; Hellmich, Martin; Shah, Ami; Chighizola, Cecilia; Denton, Christopher P.; Ong, Voon H.

In: Arthritis Research and Therapy, Vol. 16, No. 1, R53, 14.02.2014.

Research output: Contribution to journalArticle

Moinzadeh, P, Fonseca, C, Hellmich, M, Shah, A, Chighizola, C, Denton, CP & Ong, VH 2014, 'Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma', Arthritis Research and Therapy, vol. 16, no. 1, R53. https://doi.org/10.1186/ar4486
Moinzadeh, Pia ; Fonseca, Carmen ; Hellmich, Martin ; Shah, Ami ; Chighizola, Cecilia ; Denton, Christopher P. ; Ong, Voon H. / Association of anti-RNA polymerase III autoantibodies and cancer in scleroderma. In: Arthritis Research and Therapy. 2014 ; Vol. 16, No. 1.
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abstract = "Introduction: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.Methods: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.Results: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).Conclusions: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.",
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AU - Fonseca, Carmen

AU - Hellmich, Martin

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AU - Chighizola, Cecilia

AU - Denton, Christopher P.

AU - Ong, Voon H.

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N2 - Introduction: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.Methods: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.Results: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).Conclusions: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.

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