The relationship between cancer and medication exposures in systemic lupus erythaematosus:: a case-cohort study
The relationship between cancer and medication exposures in systemic lupus erythaematosus:: a case-cohort study
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DOI：
10.1136/ard.2006.069039
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发表时间：
2008-01-01
影响因子：
27.4
通讯作者：
Clarke, A. E.
中科院分区：
文献类型：
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作者：
Bernatsky, S.;Joseph, L.;Clarke, A. E.
目的：要检查，如果在系统性红斑狼疮（SLE），暴露于免疫抑制治疗（环磷酰胺，硫唑嘌呤，甲氨蝶呤）增加癌症risk.Methods：一个病例队列研究进行了一个多站点的国际SLE队列，受试者被链接到区域肿瘤登记处，以确定进入队列后发生的癌症病例。我们在控制其他药物（抗疟疾药物、全身性糖皮质激素、非甾体抗炎药（NSAID）、阿司匹林）、吸烟、年龄、性别、种族/民族、地理位置、日历年、SLE病程和狼疮损伤评分的模型中，计算了暴露于免疫抑制药物后患癌症的风险比（HR）。在主要分析中，暴露被分类处理（以往/从未），并作为timedependent.Results：结果从246例癌症和538例对照无癌症。任何免疫抑制药物治疗后的总体癌症风险的校正HR为0.82（95% CI 0.50-1.36）。年龄>= 65岁，非恶性损害的存在与总体癌症风险相关。对于肺癌（n = 35例），吸烟也是一个突出的风险因素。当特别观察血液系统癌症时（n = 46例），提示免疫抑制药物暴露后风险增加，特别是当这些药物暴露滞后5年时（校正HR 2.29，95%CI 1.02-5.15）。结论：在我们的SLE样本中，年龄≥ 65岁，损伤和烟草暴露与癌症风险相关。虽然免疫抑制治疗可能不是总体癌症风险的主要驱动因素，但它可能导致血液系统恶性肿瘤风险增加。未来的研究正在进行中，以评估药物暴露和疾病活动对恶性肿瘤风险的独立影响。
Objective: To examine if, in systemic lupus erythaematosus (SLE), exposure to immunosuppressive therapy (cyclophosphamide, azathioprine, methotrexate) increases cancer risk.Methods: A case-cohort study was performed within a multi-site international SLE cohort; subjects were linked to regional tumour registries to determine cancer cases occurring after entry into the cohort. We calculated the hazard ratio (HR) for cancer after exposure to an immunosuppressive drug, in models that controlled for other medications (anti-malarial drugs, systemic glucocorticoids, non-steroidal anti-inflammatory drugs (NSAIDs), aspirin), smoking, age, sex, race/ethnicity, geographic location, calendar year, SLE duration, and lupus damage scores. In the primary analyses, exposures were treated categorically (ever/never) and as timedependent.Results: Results are presented from 246 cancer cases and 538 controls without cancer. The adjusted HR for overall cancer risk after any immunosuppressive drug was 0.82 (95% Cl 0.50-1.36). Age >= 65, and the presence of non-malignancy damage were associated with overall cancer risk. For lung cancer (n = 35 cases), smoking was also a prominent risk factor. When looking at haematological cancers specifically (n = 46 cases), there was a suggestion of an increased risk after immunosuppressive drug exposures, particularly when these were lagged by a period of 5 years (adjusted HR 2.29, 95% Cl 1.02-5.15).Conclusions: In our SLE sample, age >= 65, damage, and tobacco exposure were associated with cancer risk. Though immunosuppressive therapy may not be the principal driving factor for overall cancer risk, it may contribute to an increased risk of haematological malignancies. Future studies are in progress to evaluate independent influence of medication exposures and disease activity on risk of malignancy.