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Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma.

ABSTRACT: We previously reported a contemporaneous onset of cancer and scleroderma in patients with anti-RNA polymerase III antibodies, and we identified a biologic link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics are associated with cancer and a clustering of cancer with scleroderma onset.Logistic regression analysis was performed to assess the relationship of 2 outcomes, cancer (model 1) and a short (±2 years) cancer-scleroderma interval (model 2), with autoantibody status and scleroderma covariates.Of 1,044 scleroderma patients, 168 (16.1%) had cancer. In the adjusted model 1, only older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.02-1.05]) and white race (odds ratio 2.71 [95% confidence interval 1.22-6.04]) were significantly associated with an increased overall risk of cancer. In the adjusted model 2, only anti-RNA polymerase III positivity (odds ratio 5.08 [95% confidence interval 1.60-16.1]) and older age at scleroderma onset (odds ratio 1.04 [95% confidence interval 1.00-1.08]) were significantly associated with a short cancer-scleroderma interval. While anti-RNA polymerase III positivity was associated with a short cancer-scleroderma interval independent of age at scleroderma onset, the cancer-scleroderma interval shortened with older age at scleroderma onset in other antibody groups (Spearman's correlation P < 0.05), particularly among patients with anti-topoisomerase I antibodies and patients who were negative for anticentromere, anti-topoisomerase I, and anti-RNA polymerase III antibodies.Increased age at scleroderma onset is strongly associated with cancer risk overall. While anti-RNA polymerase III status is an independent marker of coincident cancer and scleroderma at any age, a clustering of cancer with scleroderma is also seen in patients with anti-topoisomerase I and other autoantibody specificities who develop scleroderma at older ages.

SUBMITTER: Shah AA

PROVIDER: S-EPMC4400658 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma.

Shah Ami A AA Hummers Laura K LK Casciola-Rosen Livia L Visvanathan Kala K Rosen Antony A Wigley Fredrick M FM

Arthritis & rheumatology (Hoboken, N.J.) 20150401 4

<h4>Objective</h4>We previously reported a contemporaneous onset of cancer and scleroderma in patients with anti-RNA polymerase III antibodies, and we identified a biologic link between cancer and scleroderma. This investigation was designed to further evaluate whether autoantibody status and other characteristics are associated with cancer and a clustering of cancer with scleroderma onset.<h4>Methods</h4>Logistic regression analysis was performed to assess the relationship of 2 outcomes, cancer ...[more]

PMID: 25605296

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Project description:Although several genetic associations with scleroderma (SSc) are defined, very little is known on genetic susceptibility to SSc-associated interstitial lung disease (SSc-ILD). A number of common polymorphisms have been associated with SSc-ILD, but most have not been replicated in separate populations. Four SNPs in IRF5, and one in each of STAT4, CD226 and IRAK1, selected as having been previously the most consistently associated with SSc-ILD, were genotyped in 612 SSc patients, of European descent, of whom 394 had ILD. The control population (n?=?503) comprised individuals of European descent from the 1000 Genomes Project. After Bonferroni correction, two of the IRF5 SNPs, rs2004640 (OR (95% CI)1.30 (1.10-1.54), pcorr?=?0.015) and rs10488631 (OR 1.48 (1.14-1.92), pcorr?=?0.022), and the STAT4 SNP rs7574865 (OR 1.43 (1.18-1.73), pcorr?=?0.0015) were significantly associated with SSc compared with controls. However, none of the SNPs were significantly different between patients with SSc-ILD and controls. Two SNPs in IRF5, rs10488631 (OR 1.72 (1.24-2.39), pcorr?=?0.0098), and rs2004640 (OR 1.39 (1.11-1.75), pcorr?=?0.03), showed a significant difference in allele frequency between controls and patients without ILD, as did STAT4 rs7574865 (OR 1.86 (1.45-2.38), pcorr?=?6.6?×?10-6). A significant difference between SSc with and without ILD was only observed for STAT4 rs7574865, being less frequent in patients with ILD (OR 0.66 (0.51-0.85), pcorr?=?0.0084). In conclusion, IRF5 rs2004640 and rs10488631, and STAT4 rs7574865 were significantly associated with SSc as a whole. Only STAT4 rs7574865 showed a significant difference in allele frequency in SSc-ILD, with the T allele being protective against ILD.Key points• We confirm the associations of the IRF5 SNPs rs2004640 and rs10488631, and the STAT4 SNP rs7574865, with SSc as a whole.• None of the tested SNPs were risk factors for SSc-ILD specifically.• The STAT4 rs7574865 T allele was protective against the development of lung fibrosis in SSc patients.• Further work is required to understand the genetic basis of lung fibrosis in association with scleroderma.

Dataset Information

Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma.

Publications

Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma.

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