Moinzadeh Pia, Fonseca Carmen, Hellmich Martin, Shah Ami A, Chighizola Cecilia, Denton Christopher P, Ong Voon H
Arthritis Res Ther. 2014 Feb 14;16(1):R53. doi: 10.1186/ar4486.
We assessed the profile and frequency of malignancy subtypes in a large single-centre UK cohort for patients with scleroderma (systemic sclerosis; SSc). We evaluated the cancer risk among SSc patients with different antibody reactivities and explored the temporal association of cancer with the duration between SSc onset and cancer diagnosis.
We conducted a retrospective study of a well-characterised cohort of SSc patients attending a large tertiary referral centre, with clinical data collected from our clinical database and by review of patient records. We evaluated development of all cancers in this cohort, and comparison was assessed with the SSc cohort without cancer. The effect of demographics and clinical details, including antibody reactivities, were explored to find associations relevant to the risk for development of cancer in SSc patients.
Among 2,177 patients with SSc, 7.1% had a history of cancer, 26% were positive for anticentromere antibodies (ACAs), 18.2% were positive for anti-Scl-70 antibodies and 26.6% were positive for anti-RNA polymerase III (anti-RNAP) antibody. The major malignancy cancer subtypes were breast (42.2%), haematological (12.3%), gastrointestinal (11.0%) and gynaecological (11.0%). The frequency of cancers among patients with RNAP (14.2%) was significantly increased compared with those with anti-Scl-70 antibodies (6.3%) and ACAs (6.8%) (P < 0.0001 and P < 0.001, respectively). Among the patients, who were diagnosed with cancer within 36 months of the clinical onset of SSc, there were more patients with RNAP (55.3%) than those with other autoantibody specificities (ACA = 23.5%, P < 0.008; and anti-Scl-70 antibodies = 13.6%, P < 0.002, respectively). Breast cancers were temporally associated with onset of SSc among patients with anti-RNAP, and SSc patients with anti-RNAP had a twofold increased hazard ratio for cancers compared to patients with ACAs (P < 0.0001).
Our study independently confirms, in what is to the best of our knowledge the largest population examined to date, that there is an association with cancer among SSc patients with anti-RNAP antibodies in close temporal relationship to onset of SSc, which supports the paraneoplastic phenomenon in this subset of SSc cases. An index of cautious suspicion should be maintained in these cases, and investigations for underlying malignancy should be considered when clinically appropriate.
我们评估了英国一个大型单中心硬皮病（系统性硬化症；SSc）患者队列中恶性肿瘤亚型的特征和频率。我们评估了具有不同抗体反应性的SSc患者的癌症风险，并探讨了癌症与SSc发病至癌症诊断之间的时间关联。
我们对一个在大型三级转诊中心就诊的特征明确的SSc患者队列进行了回顾性研究，临床数据从我们的临床数据库收集并通过查阅患者记录获得。我们评估了该队列中所有癌症的发生情况，并与无癌症的SSc队列进行了比较。探讨了人口统计学和临床细节（包括抗体反应性）的影响，以寻找与SSc患者癌症发生风险相关的关联。
在2177例SSc患者中，7.1%有癌症病史，26%抗着丝点抗体（ACA）阳性，18.2%抗Scl - 70抗体阳性，26.6%抗RNA聚合酶III（抗RNAP）抗体阳性。主要的恶性肿瘤亚型为乳腺癌（42.2%）、血液系统肿瘤（12.3%）、胃肠道肿瘤（11.0%）和妇科肿瘤（11.0%）。抗RNAP抗体阳性患者的癌症发生率（14.2%）与抗Scl - 70抗体阳性患者（6.3%）和ACA阳性患者（6.8%）相比显著增加（分别为P < 0.0001和P < 0.001）。在SSc临床发病36个月内被诊断出癌症的患者中，抗RNAP抗体阳性的患者（55.3%）多于其他自身抗体特异性患者（ACA = 23.5%，P < 0.008；抗Scl - 70抗体 = 13.6%，P < 0.002）。在抗RNAP抗体阳性的患者中，乳腺癌与SSc发病在时间上相关，与ACA阳性患者相比，抗RNAP抗体阳性的SSc患者患癌症的风险比增加了两倍（P < 0.0001）。
据我们所知，我们的研究在迄今为止检查的最大人群中独立证实，抗RNAP抗体阳性且与SSc发病时间密切相关的SSc患者与癌症存在关联，这支持了这一SSc病例亚组中的副肿瘤现象。在这些病例中应保持谨慎怀疑的态度，并且在临床适当时应考虑对潜在恶性肿瘤进行检查。
