Evaluation of six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon therapy in the He13A/98 multicenter trial

Journal of Translational Medicine

Research

Elizabeth Buchbinder¹  Michael B Atkins¹  Henry Koon²  Alexandros Stratigos³  Maria Spyropoulou-Vlachou⁴  George Fountzilas⁵  Dimosthenis Tsoutsos⁶  Petros Panagiotou⁶  Ourania Castana⁷  Yannis Metaxas⁸  Helen Gogas⁸  Aristidis Polyzos⁸  Christos Markopoulos⁸  Eirini Pectasides⁸  Pantelis Skarlos⁹  John M Kirkwood^1,10  Urania Dafni^1,11 

[1] Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA;Case Comprehensive Cancer Center, University Hospital Case Medical Center, Cleveland, OH, USA;Department of Dermatology, University of Athens, "Andreas Sygros" Hospital, Athens, Greece;Department of Immunology, National Tissue Typing Center, General Hospital of Athens, Greece;Department of Medical Oncology, Papageorgiou Hospital, Aristotle University of Thessaloniki, School of Medicine, Thessaloniki, Greece;Department of Plastic Surgery and Microsurgery, G. Gennimatas General Hospital of Athens, Greece;Department of Plastic Surgery, Evagelismos Hospital, Athens, Greece;First Department of Medicine, University of Athens, Medical School, Athens, Greece;Hellenic Cooperative Oncology Group, Data Office, Athens, Greece;Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA;Laboratory of Biostatistics, University of Athens School of Nursing, Athens, Greece;

关键词: Melanoma;    Overall Survival;    Sentinel Lymph Node;    Melanoma Patient;    Ipilimumab;   

DOI  :  10.1186/1479-5876-8-108

 received in 2010-09-09, accepted in 2010-11-03,  发布年份 2010

来源: Springer

【 摘 要 】

PurposeInterferon 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.Experimental design286 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.ResultsNo 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.ConclusionNo 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.

【 授权许可】

CC BY   
© Gogas et al; licensee BioMed Central Ltd. 2010