Abstract
CTLA-4 blockade with monoclonal antibodies can lead to cancer regression in patients with metastatic melanoma (MM). CTLA-4 gene polymorphisms may influence the response to anti-CTLA-4 antibodies although few data are available regarding this issue. We analyzed six CTLA-4 single nucleotide polymorphisms (-1661A > G, -1577G > A, -658C > T, -319C > T, +49A > G, and CT60G > A) in 14 Italian MM patients and 45 healthy subjects. We found a significant association between the -1577G/A and CT60G/A genotypes and improved overall survival (Pc < 0.006, Bonferroni corrected), further confirmed by the diplotype analysis (-1577 & CT60 GG-AA diplotype, p < 0.001). A positive trend toward an association between these genotypes and response to therapy was also observed.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antibodies, Monoclonal / pharmacology
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Antibodies, Monoclonal / therapeutic use*
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Autoimmunity
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Base Sequence
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CTLA-4 Antigen / antagonists & inhibitors
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CTLA-4 Antigen / genetics*
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Case-Control Studies
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Clinical Trials, Phase II as Topic
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Female
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Gene Frequency
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Genetic Association Studies
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Humans
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Ipilimumab
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Kaplan-Meier Estimate
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Male
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Melanoma / drug therapy
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Melanoma / genetics*
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Melanoma / mortality
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Melanoma / secondary
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Middle Aged
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Multicenter Studies as Topic
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Pilot Projects
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Polymorphism, Single Nucleotide*
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Sequence Analysis, DNA
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Skin Neoplasms / drug therapy
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Skin Neoplasms / genetics*
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Skin Neoplasms / mortality
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Skin Neoplasms / pathology
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Treatment Outcome
Substances
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Antibodies, Monoclonal
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Antineoplastic Agents
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CTLA-4 Antigen
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Ipilimumab