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Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer
  1. Takeru Igusa1,
  2. Laura K Hummers2,
  3. Kala Visvanathan3,
  4. Carrie Richardson2,
  5. Fredrick M Wigley2,
  6. Livia Casciola-Rosen,
  7. Antony Rosen2,
  8. Ami A Shah2
  1. 1 Departments of Civil Engineering and Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland, USA
  2. 2 Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  3. 3 Departments of Epidemiology and Medical Oncology, Johns Hopkins Bloomberg School of Public Health and Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
  1. Correspondence to Dr. Ami A Shah, Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA; Ami.Shah{at}


Objectives Recent studies demonstrate autoantibodies are powerful tools to interrogate molecular events linking cancer and the development of autoimmunity in scleroderma. Investigating cancer risk in these biologically relevant subsets may provide an opportunity to develop personalised cancer screening guidelines. In this study, we examined cancer risk in distinct serologic and phenotypic scleroderma subsets and compared estimates with the general population.

Methods Patients in the Johns Hopkins Scleroderma Center observational cohort were studied. Overall and site-specific cancer incidence was calculated in distinct autoantibody and scleroderma phenotypic subsets, and compared with the Surveillance, Epidemiology and End Results registry, a representative sample of the US population.

Results 2383 patients with scleroderma contributing 37 686 person-years were studied. 205 patients (8.6%) had a diagnosis of cancer. Within 3 years of scleroderma onset, cancer risk was increased in patients with RNA polymerase III autoantibodies (antipol; standardised incidence ratio (SIR) 2.84, 95% CI 1.89 to 4.10) and those lacking centromere, topoisomerase-1 and pol antibodies (SIR 1.83, 95% CI 1.10 to 2.86). Among antipol-positive patients, cancer-specific risk may vary by scleroderma subtype; those with diffuse scleroderma had an increased breast cancer risk, whereas those with limited scleroderma had high lung cancer risk. In contrast, patients with anticentromere antibodies had a lower risk of cancer during follow-up (SIR 0.59, 95% CI 0.44 to 0.76).

Conclusions Autoantibody specificity and disease subtype are biologically meaningful filters that may inform cancer risk stratification in patients with scleroderma. Future research testing the value of targeted cancer screening strategies in patients with scleroderma is needed.

  • systemic sclerosis
  • autoantibodies
  • epidemiology

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  • 29 Ar and AAS are joint senior authors

  • 30 TI, LKH and KV are joint first authors

  • Handling editor Josef S Smolen

  • Funding This study was supported by the NIH (K23-AR061439, P30-AR053503, P30-AR070254, R01- DE12354-15A1, T32-AR048522), the Donald B and Dorothy L Stabler Foundation, the Jerome L Greene Foundation, the Chresanthe Stauralakis Memorial Discovery Fund, the Martha McCrory Professorship and the Scleroderma Research Foundation.

  • Competing interests TI, LC-R, AR and AAS have recently submitted a patent application entitled ’Materials and Methods for Assessing Cancer Risk and Treating Cancer'.

  • Patient consent Not required.

  • Ethics approval Johns Hopkins Medical Institutions IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement There are no additional unpublished data from this study at this time.