Yanik E L, Gustafson S K, Kasiske B L, Israni A K, Snyder J J, Hess G P, Engels E A, Segev D L
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.
Am J Transplant. 2015 Jan;15(1):129-36. doi: 10.1111/ajt.12969. Epub 2014 Dec 17.
Sirolimus has anti-carcinogenic properties and can be included in maintenance immunosuppressive therapy following kidney transplantation. We investigated sirolimus effects on cancer incidence among kidney recipients. The US transplant registry was linked with 15 population-based cancer registries and national pharmacy claims. Recipients contributed sirolimus-exposed time when sirolimus claims were filled, and unexposed time when other immunosuppressant claims were filled without sirolimus. Cox regression was used to estimate associations with overall and specific cancer incidence, excluding nonmelanoma skin cancers (not captured in cancer registries). We included 32,604 kidney transplants (5687 sirolimus-exposed). Overall, cancer incidence was suggestively lower during sirolimus use (hazard ratio [HR] = 0.88, 95% confidence interval [CI] = 0.70-1.11). Prostate cancer incidence was higher during sirolimus use (HR = 1.86, 95% CI = 1.15-3.02). Incidence of other cancers was similar or lower with sirolimus use, with a 26% decrease overall (HR = 0.74, 95% CI = 0.57-0.96, excluding prostate cancer). Results were similar after adjustment for demographic and clinical characteristics. This modest association does not provide strong evidence that sirolimus prevents posttransplant cancer, but it may be advantageous among kidney recipients with high cancer risk. Increased prostate cancer diagnoses may result from sirolimus effects on screen detection.
西罗莫司具有抗癌特性,可用于肾移植后的维持性免疫抑制治疗。我们研究了西罗莫司对肾移植受者癌症发病率的影响。美国移植登记处与15个基于人群的癌症登记处和国家药房索赔数据相链接。当填写西罗莫司索赔时,受者贡献了西罗莫司暴露时间;当填写其他免疫抑制剂索赔而无西罗莫司时,受者贡献了未暴露时间。采用Cox回归估计与总体和特定癌症发病率的关联,不包括非黑色素瘤皮肤癌(癌症登记处未记录)。我们纳入了32604例肾移植(5687例有西罗莫司暴露)。总体而言,使用西罗莫司期间癌症发病率有降低趋势(风险比[HR]=0.88,95%置信区间[CI]=0.70-1.11)。使用西罗莫司期间前列腺癌发病率较高(HR=1.86,95%CI=1.15-3.02)。使用西罗莫司时其他癌症的发病率相似或更低,总体下降26%(HR=0.74,95%CI=0.57-0.96,不包括前列腺癌)。在调整人口统计学和临床特征后结果相似。这种适度的关联并不能有力证明西罗莫司可预防移植后癌症,但对于癌症风险高的肾移植受者可能有益。前列腺癌诊断增加可能是西罗莫司对筛查检测产生影响所致。