Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial.
Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial.
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DOI：
10.1186/1479-5876-8-108
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发表时间：
2010-11-03
影响因子：
7.4
通讯作者：
Kirkwood JM
中科院分区：
文献类型：
--
作者：
Gogas H;Dafni U;Koon H;Spyropoulou-Vlachou M;Metaxas Y;Buchbinder E;Pectasides E;Tsoutsos D;Polyzos A;Stratigos A;Markopoulos C;Panagiotou P;Fountzilas G;Castana O;Skarlos P;Atkins MB;Kirkwood JM
干扰素被批准用于IIb/III期黑色素瘤患者的辅助治疗。干扰素的毒性和对生存益处的不确定性限制了它的接受，尽管在一小部分患者中有显著的持久复发预防作用。能够选择接受治疗的患者的预测性生物标志物将对临床实践产生重大影响。先前研究表明，转移性黑色素瘤患者对CTLA-4阻断的反应和自身免疫的发展与特定的CTLA-4基因多态性有关。对286例黑色素瘤患者和288例健康对照进行了6个以前认为重要的CTLA-4基因(AG 49、CT 318、CT 60、JO 27、JO30和JO 31)的基因分型。比较了健康人群和患者群体之间的特定等位基因频率，以及这些等位基因的存在或不存在与复发的关系。对自身免疫性疾病的相关等位基因也进行了研究。CTLA-4基因多态性在黑色素瘤人群中的分布与健康对照无显著差异。无复发生存期(RFS)和总生存期(OS)在这些多态所代表的等位基因患者之间没有显著差异。自身免疫与特异性等位基因之间无相关性。这六个多态被评估在强关联的地方(所有关联的费舍尔精确p值和0.001)和这些之间的显著连锁不平衡被指出。在这组黑色素瘤高危患者中，所研究的SNPs所定义的CTLA-4基因多态性与改善的RFS、OS或自身免疫没有相关性。
Interferon is approved for adjuvant treatment of patients with stage IIb/III melanoma. The toxicity and uncertainty regarding survival benefits of interferon have qualified its acceptance, despite significant durable relapse prevention in a fraction of patients. Predictive biomarkers that would enable selection of patients for therapy would have a large impact upon clinical practice. Specific CTLA-4 polymorphisms have previously shown an association with response to CTLA-4 blockade in patients with metastatic melanoma and the development of autoimmunity. 286 melanoma patients and 288 healthy controls were genotyped for six CTLA-4 polymorphisms previously suggested to be important (AG 49, CT 318, CT 60, JO 27, JO30 and JO 31). Specific allele frequencies were compared between the healthy and patient populations, as well as presence or absence of these in relation to recurrence. Alleles related to autoimmune disease were also investigated. No significant differences were found between the distributions of CTLA-4 polymorphisms in the melanoma population compared with healthy controls. Relapse free survival (RFS) and overall survival (OS) did not differ significantly between patients with the alleles represented by these polymorphisms. No correlation between autoimmunity and specific alleles was shown. The six polymorphisms evaluated where strongly associated (Fisher's exact p-values < 0.001 for all associations) and significant linkage disequilibrium among these was indicated. No polymorphisms of CTLA-4 defined by the SNPs studied were correlated with improved RFS, OS, or autoimmunity in this high-risk group of melanoma patients.
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影响因子：
20.3
作者：
Pérez-García, Arianne;De la Cámara, Rafael;Gallardo, David
通讯作者：
Gallardo, David
影响因子：
158.5
作者：
Gogas, H;Ioannovich, J;Kirkwood, JM
通讯作者：
Kirkwood, JM
影响因子：
3.9
作者：
Rosenberg, SA;White, DE
通讯作者：
White, DE
影响因子：
5.4
作者：
DARIAVACH, P;MATTEI, MG;LEFRANC, MP
通讯作者：
LEFRANC, MP
影响因子：
3.5
作者：
Furugaki, K;Shirasawa, S;Sasazuki, T
通讯作者：
Sasazuki, T