Departments of Civil Engineering and Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, Maryland, USA.
Division of Rheumatology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Ann Rheum Dis. 2018 Aug;77(8):1179-1186. doi: 10.1136/annrheumdis-2018-212999. Epub 2018 Apr 20.
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.
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.
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).
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.
最近的研究表明，自身抗体是探究癌症与硬皮病自身免疫发生之间分子事件的有力工具。研究这些具有生物学相关性的亚组中的癌症风险可能为制定个性化癌症筛查指南提供机会。在本研究中，我们检查了不同血清学和表型硬皮病亚组中的癌症风险，并将这些估计值与普通人群进行了比较。
研究了约翰霍普金斯硬皮病中心观察队列中的患者。在不同的自身抗体和硬皮病表型亚组中计算了总体和特定部位的癌症发病率，并与监测、流行病学和最终结果登记处（美国人口的代表性样本）进行了比较。
研究了 2383 名患有硬皮病的患者，共贡献了 37686 人年。205 名患者（8.6%）被诊断患有癌症。在硬皮病发病后的 3 年内，RNA 聚合酶 III 自身抗体阳性（抗-pol；标准化发病比（SIR）2.84，95%CI 1.89 至 4.10）和缺乏着丝粒、拓扑异构酶-1 和 pol 抗体的患者（SIR 1.83，95%CI 1.10 至 2.86）的癌症风险增加。在抗-pol 阳性患者中，癌症的特定风险可能因硬皮病亚型而异；弥漫性硬皮病患者乳腺癌风险增加，而局限性硬皮病患者肺癌风险较高。相比之下，抗着丝粒抗体阳性的患者在随访期间癌症风险较低（SIR 0.59，95%CI 0.44 至 0.76）。
自身抗体特异性和疾病亚型是具有生物学意义的筛选因素，可能为硬皮病患者的癌症风险分层提供信息。需要进一步研究来检验在硬皮病患者中应用靶向癌症筛查策略的价值。
