Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Nephrol Dial Transplant. 2010 Aug;25(8):2764-71. doi: 10.1093/ndt/gfp425. Epub 2009 Sep 3.
The risk of cutaneous squamous cell carcinoma (CSCC) is found to be substantially increased after organ transplantation. The association with specific immunosuppressive regimens has been previously investigated, but results are not concordant. We aimed to clarify the relationship between separate immunosuppressive drugs, drug load, timing and risk of post-transplant CSCC.
A population-based nested case-control study was performed in the Swedish organ transplantation cohort (n = 5931). All patients who developed CSCC during the follow-up (1970-97) were eligible as cases (n = 207). Controls (n = 189) were randomly selected from the cohort and individually matched to the cases on follow-up time, age at and calendar period of transplantation. Exposure information was collected through extensive and standardized review of medical records.
The median time to CSCC was 6.7 years. Post-transplant azathioprine (Aza) treatment considerably increased the risk of CSCC during all time periods analysed, and the risk augmented with increasing dose and duration. Patients who after the entire follow-up period had received a high accumulated dose of Aza had an 8.8-fold increased risk of CSCC in multivariate analysis (P < 0.0001), compared to patients never treated with Aza. Additionally, a high accumulated dose of corticosteroids during the same period conferred a 3.9-fold elevated risk of CSCC (P = 0.09), compared to the lowest accumulated dose of corticosteroids. Cyclosporine treatment was not associated with the risk of CSCC post-transplantation.
This study provides evidence that Aza treatment, but not cyclosporine treatment, is strongly associated with post-transplant CSCC risk. The results suggest that the risk of CSCC after organ transplantation is not only an effect of the immunosuppressive load per se.
器官移植后，皮肤鳞状细胞癌（CSCC）的风险显著增加。先前已经研究了与特定免疫抑制方案的关联，但结果并不一致。我们旨在阐明单独的免疫抑制剂药物、药物负荷、时间和移植后 CSCC 的风险之间的关系。
在瑞典器官移植队列（n = 5931）中进行了一项基于人群的巢式病例对照研究。在随访期间（1970-97 年）发生 CSCC 的所有患者均有资格作为病例（n = 207）。对照（n = 189）是从队列中随机选择的，并按随访时间、移植时年龄和日历时间与病例进行个体匹配。通过对医疗记录进行广泛和标准化的审查来收集暴露信息。
CSCC 的中位时间为 6.7 年。移植后使用硫唑嘌呤（Aza）治疗在分析的所有时间段内都大大增加了 CSCC 的风险，并且风险随着剂量和持续时间的增加而增加。在整个随访期间接受高累积 Aza 剂量的患者在多变量分析中 CSCC 的风险增加了 8.8 倍（P < 0.0001），与从未接受过 Aza 治疗的患者相比。此外，同一时期高累积剂量的皮质类固醇与 CSCC 的风险增加 3.9 倍（P = 0.09）相比，最低累积剂量的皮质类固醇。环孢素治疗与移植后 CSCC 的风险无关。
本研究提供的证据表明，Aza 治疗，而不是环孢素治疗，与移植后 CSCC 风险密切相关。结果表明，器官移植后 CSCC 的风险不仅是免疫抑制负荷本身的影响。
