RELATION BETWEEN SKIN-CANCER AND HLA ANTIGENS IN RENAL-TRANSPLANT RECIPIENTS
RELATION BETWEEN SKIN-CANCER AND HLA ANTIGENS IN RENAL-TRANSPLANT RECIPIENTS
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DOI：
10.1056/nejm199109193251203
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发表时间：
1991-09-19
影响因子：
158.5
通讯作者：
CLAAS, FHJ
中科院分区：
文献类型：
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作者：
BAVINCK, JNB;VERMEER, BJ;CLAAS, FHJ
背景资料。接受同种异体肾移植的人患皮肤癌的风险增加。我们还知道，人类白细胞抗原纯合子的受者患某些癌症的风险增加，那些与捐赠者在这些抗原上不匹配的受者也是如此。在一项病例对照研究中，我们评估了肾移植受者皮肤癌与人类白细胞抗原纯合子和错配的关系。在1966至1988年间接受肾移植的764名患者中，66人在移植后患上了皮肤鳞状细胞癌或基底细胞癌。对所有66例受者进行了人类白细胞抗原纯合子检测，并对39例受者进行了检测，并与124例未患皮肤癌的受者进行了比较。我们还调查了皮肤癌与免疫抑制药物的使用之间的关系。在单独的病例对照分析中，我们调查了暴露在阳光下和角化性皮肤损害对皮肤癌风险的影响。HLA-B抗原错配的受者患鳞状细胞癌的风险增加；与未错配的受者相比，其中一种和两种抗原错配的相对风险分别为2.6(95%可信区间，1.1~6.5)和5.0(95%可信区间，1.3~19.0)。人类白细胞抗原-A或人类白细胞抗原-DR的不匹配对鳞状细胞癌的风险没有影响，并且任何一个人类白细胞抗原基因座的不匹配与基底细胞癌的发生之间没有关联。硫唑嘌呤和强的松的总剂量与皮肤癌的发生或与人类白细胞抗原配型无关。皮损处暴露在阳光下和角化滑雪板与皮肤癌密切相关，但与人类白细胞抗原不匹配无关。在鳞状细胞癌患者(相对风险为2.5；95%可信区间为0.95~4.6)和有100个或以上角化性皮肤病变的患者(相对风险为4.8；95%可信区间为1.5至15.1)中，人类白细胞抗原-DR纯合子的频率更高。在肾移植受者中，人类白细胞抗原B不匹配与鳞状细胞癌的风险显著相关，与人类白细胞抗原DR纯合子也是如此。免疫抑制水平的间接影响似乎不能解释这些发现，暴露在阳光下或角化性皮肤病变的数量也不能解释这一观察结果。
Background. Recipients of renal allografts are at an increased risk for skin cancer. It is also known that recipients who are homozygous for HLA antigens are at an increased risk for certain cancers, as are those who are mismatched with their donors for these antigens. In a case-control study we assessed the relation between skin cancer in renal-transplant recipients and HLA homozygosity and mismatching.Methods. Of 764 patients who received renal transplants between 1966 and 1988, 66 had squamous-cell carcinoma or basal-cell carcinoma of the skin after transplantation. HLA homozygosity was assessed in all 66 recipients, and HLA mismatching in 39; the results were compared with those in 124 recipients without skin cancer. We also investigated the relation between skin cancer and the use of immunosuppressive drugs. In separate case-control analyses we investigated the influence of exposure to the sun and keratotic skin lesions on the risk of skin cancer.Results. The risk of squamous-cell carcinoma was increased in recipients mismatched for HLA-B antigens; the relative risks were 2.6 (95 percent confidence interval, 1.1 to 6.5) and 5.0 (95 percent confidence interval, 1.3 to 19.0) with mismatching for one and two antigens, respectively, as compared with no mismatching. Mismatching for HLA-A or HLA-DR antigens had no effect on the risk of squamous-cell carcinoma, and there was no association between mismatches at any of the HLA loci and the occurrence of basal-cell carcinoma. The total doses of azathioprine and prednisone were not associated with the occurrence of skin cancer or with HLA matching. Exposure to sunlight and keratotic ski in lesions were strongly associated with skin cancer but not with HLA mismatching. Homozygosity for HLA-DR was more frequent among the patients with squamous-cell carcinoma (relative risk, 2.5; 95 percent confidence interval, 0.95 to 4.6) and among patients with 100 or more keratotic skin lesions (relative risk, 4.8; 95 percent confidence interval, 1.5 to 15.1).Conclusions. HLA-B mismatching is significantly associated with the risk of squamous-cell carcinoma in renal-transplant recipients, as is HLA-DR homozygosity. An indirect effect on the level of immunosuppression does not appear to explain these findings, nor does exposure to sunlight or the number of keratotic skin lesions account for this observation.