TY - JOUR
T1 - Autoantibodies and scleroderma phenotype define subgroups at high-risk and low-risk for cancer
AU - Igusa, Takeru
AU - Hummers, Laura K.
AU - Visvanathan, Kala
AU - Richardson, Carrie
AU - Wigley, Fredrick M.
AU - Casciola-Rosen, Livia
AU - Rosen, Antony
AU - Shah, Ami A.
N1 - Funding Information:
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.
Funding Information:
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.
Publisher Copyright:
© Article author(s)2018. All rights reserved.
PY - 2018/8/1
Y1 - 2018/8/1
N2 - 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.
AB - 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.
KW - Systemic sclerosis
KW - autoantibodies
KW - epidemiology
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U2 - 10.1136/annrheumdis-2018-212999
DO - 10.1136/annrheumdis-2018-212999
M3 - Article
C2 - 29678941
AN - SCOPUS:85049029024
SN - 0003-4967
VL - 77
SP - 1180
EP - 1187
JO - Annals of the rheumatic diseases
JF - Annals of the rheumatic diseases
IS - 8
ER -