Immunosuppression and risk of non-melanoma skin cancer in renal transplant recipients
Immunosuppression and risk of non-melanoma skin cancer in renal transplant recipients
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DOI：
10.1016/s0140-6736(97)80015-3
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发表时间：
1997-02-08
期刊：
影响因子：
168.9
通讯作者：
Leigh, IM
中科院分区：
文献类型：
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作者：
Glover, MT;Deeks, JJ;Leigh, IM
非黑色素瘤皮肤癌（NMSC）在肾移植受者中的发生率高于一般人群。几个风险因素已被确认，包括肤色白皙，高日照，首次移植时年龄较大，但不同的免疫抑制方案的作用尚不清楚。为了探讨免疫抑制患者环孢素，硫唑嘌呤和泼尼松龙（CAP）比患者接受硫唑嘌呤和泼尼松龙（AP）更有可能发展NMSC的可能性，我们进行了一项历史队列研究。患者完成了一份问卷，详细说明了一生的阳光照射和皮肤类型。常规记录免疫抑制药物的平均日剂量、首次移植时的年龄、移植日期、性别、透析时间和HLA错配状态。接受者被分类为接受CAP或AP。考克斯比例风险模型用于估计两种免疫抑制方案对NMSC发生率的影响，控制已知的风险因素。有295例患者的数据可用。在33名被排除在进一步分析之外的非洲黑人或亚洲患者中未发现NMSC。51例（19%）接受者至少有一个NMSC; 30例基底细胞癌，21例鳞状细胞癌，22例原位鳞状细胞癌。接受AP的82名接受者的NMSC发病率为29/1000人-年（表）。另外接受环孢菌素治疗的180例受者的NMSC发生率增加了48例/1000人-年（风险比3.36 [95% CI 1.50-7.481，p= 0.003）。CAP组的恶性肿瘤发生较早。在1984年10月之前移植的患者中，97%接受了AP，而最近移植的患者中有94%接受了CAP。CAP组倾向于年龄更大，在移植前透析时间更长，并且有更多的HLA不匹配。校正危险因素后，鳞状细胞癌仍有较大的显著性增加（校正后风险比为8.43 [1.30-54.8]，p= 0.03），但基底细胞癌无显著性增加（校正后风险比为1.48 [0.45-4.88]，p= 0.5）。在我们的研究中，接受CAP的患者发生鳞状细胞癌的风险特别高，但不是基底细胞癌。这种增加可能部分是由于皮肤病学监测的改善而造成的，但这不太可能是完整的解释，因为（i）仅在鳞状细胞癌中观察到增加，而在基底细胞癌中没有观察到增加，并且（ii）存活曲线表明AP组中鳞状细胞癌的发病率落后于对照组。
Non-melanoma skin cancer (NMSC) occurs more frequently in renal transplant recipients than in the general population.’Several risk factors are recognised including fair complexion, high sun-exposure, and greater age at first transplant,’but the role of different immunosuppressive regimens is unclear. To explore the possibility that patients immunosuppressed with cyclosporin, azathioprine, and prednisolone (CAP) were more likely to develop NMSC than patients receiving azathioprine and prednisolone (AP) we undertook a historical cohort study.Patients with functioning renal transplants attending this hospital are regularly examined for skin cancer. Patients completed a questionnaire detailing life-time sun-exposure and skin type. Mean daily doses of immunosuppressive drugs, age at first transplant, and date of transplant, gender, time on dialysis, and HLA mismatch status are routinely recorded. Recipients were classified as receiving CAP or AP. Cox proportional hazard models were used to estimate the effect of the two immunosuppressive regimens on NMSC incidence controlling for known risk factors. Data were available on 295 patients. No NMSC was found in the 33 Black African or Asian patients who were excluded from further analysis. 51 (19%) recipients had a least one NMSC; 30 had basal-cell carcinoma, 2 1 had squamous-cell carcinoma, and 22 had in-situ squamous-cell carcinoma. The 82 recipients receiving AP had an incidence rate of 29 NMSC per 1000 person-years (table). The 180 recipients who additionally received cyclosporin had an increased incidence of 48 NMSC per 1000 person-years (hazard ratio 3.36 [95% CI 1.50-7.481, p= 0.003). The malignancies in the CAP group occurred earlier. 97% of those transplanted before October, 1984, received AP whilst 94% of those transplanted more recently received CAP. The CAP group tended to be older, to have spent longer on dialysis before transplantation, and to have more HLA mismatches. After adjustment for risk factors a large significant increase in squamous-cell carcinoma remained (adjusted hazard ratio 8.43 [1.30-54.8], p= 0.03) but not for basal-cell carcinoma (adjusted hazard ratio 1.48 [0.45-4.88], p= 0.5). In our study patients receiving CAP were at particularly high risk of squamous-cell carcinoma but not basal-cell carcinoma. It is possible that this increase is in part an artifact created by improvements in dermatological surveillance but it is unlikely that this is the complete explanation, because (i) the increase was observed only for squamous-cell carcinoma and not basal-cell carcinoma, and (ii) the survival curves indicate that the incidence of squamous-cell carcinoma in the AP group lags behind the