Abdulla Watad1,2,3, Dennis McGonagle3, Nicola L Bragazzi4, Shmuel Tiosano1,2, Doron Comaneshter5, Yehuda Shoenfeld1,2, Arnon D Cohen5,6, Howard Amital1,2. 1. Department of Medicine 'B', The Zabludowicz Center for Autoimmune Diseases, Sheba Medical Center, Ramat Gan, Israel. 2. Sackler Faculty of Medicine, Tel-Aviv University, Tel Aviv-Yafo, Israel. 3. Section of Musculoskeletal Disease, Leeds Institute of Molecular Medicine, University of Leeds, NIHR Leeds Musculoskeletal Biomedical Research Unit, Chapel Allerton Hospital, Leeds, UK. 4. School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, Genoa, Italy. 5. Chief Physician's Office, Clalit Health Services Tel Aviv, Tel-Aviv, Israel. 6. Siaal Research Center for Family Medicine and Primary Care, Faculty of Health Sciences, Ben Gurion University of the Negev, Beer Sheva, Israel.
Abstract
Background: A higher rate of cancer in systemic sclerosis (SSc) is recognized but the role of SSc-linked autoantibodies status (positive/negative and autoantibody specificities) in the survival of SSc-patients with cancer remains poorly understood. Methods: We utilized the Clalit-Health-Services medical database in a case-control study to evaluate the autoantibody status and specificities of SSc-patients with age- and sex-matched controls with regard to the prevalence of different cancer-subtypes and their impact on mortality. SSc-linked autoantibodies (ANA, anti-centromere, anti-RNP, anti-RNA polymerase III (RNAPIII) and anti-Scl-70) status was assessed in terms of cancer risk and outcome. Results: 2,431 SSc-patients and 12,377 age- and sex-matched controls were included. SSc-patients had a relative risk of cancer of 1.90 (95%CI 1.62-2.24, p < 0.0001) and tended to develop malignancies earlier than controls. RNAPIII and Scl-70 autoantibody were associated with an increased overall cancer risk and after SSc diagnosis risk of cancer, respectively. As expected, SSc-patients with cancer had a risk of death of 2.15 (1.65-2.79) in comparison to SSc-patients without cancer. ANA-positive SSc-patients with cancer had a better prognosis than ANA-negative cases (p = 0.0001). Despite the benefit of ANA-positive status on survival, the anti-Scl-70-positive subgroup with cancer had a significant negative impact on the survival compared to Scl-70-positive cases without cancer, whereas anti-RNAPIII and anti-centromere had no significant impact. Conclusion: ANA positivity is an independent predictor of favorable prognosis in SSc-patients with cancer, possibly suggesting that humoral autoimmunity in SSc with cancer may have some benefit. However, no survival benefit was discernible with the common autoantibodies.
Background: A higher rate of cancer in systemic sclerosis (SSc) is recognized but the role of SSc-linked autoantibodies status (positive/negative and autoantibody specificities) in the survival of SSc-patients with cancer remains poorly understood. Methods: We utilized the Clalit-Health-Services medical database in a case-control study to evaluate the autoantibody status and specificities of SSc-patients with age- and sex-matched controls with regard to the prevalence of different cancer-subtypes and their impact on mortality. SSc-linked autoantibodies (ANA, anti-centromere, anti-RNP, anti-RNA polymerase III (RNAPIII) and anti-Scl-70) status was assessed in terms of cancer risk and outcome. Results: 2,431 SSc-patients and 12,377 age- and sex-matched controls were included. SSc-patients had a relative risk of cancer of 1.90 (95%CI 1.62-2.24, p < 0.0001) and tended to develop malignancies earlier than controls. RNAPIII and Scl-70 autoantibody were associated with an increased overall cancer risk and after SSc diagnosis risk of cancer, respectively. As expected, SSc-patients with cancer had a risk of death of 2.15 (1.65-2.79) in comparison to SSc-patients without cancer. ANA-positive SSc-patients with cancer had a better prognosis than ANA-negative cases (p = 0.0001). Despite the benefit of ANA-positive status on survival, the anti-Scl-70-positive subgroup with cancer had a significant negative impact on the survival compared to Scl-70-positive cases without cancer, whereas anti-RNAPIII and anti-centromere had no significant impact. Conclusion: ANA positivity is an independent predictor of favorable prognosis in SSc-patients with cancer, possibly suggesting that humoral autoimmunity in SSc with cancer may have some benefit. However, no survival benefit was discernible with the common autoantibodies.
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