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

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.