Association of CTLA-4 polymorphisms with improved overall survival in melanoma patients treated with CTLA-4 blockade: a pilot study

Cancer Invest. 2013 Jun;31(5):336-45. doi: 10.3109/07357907.2013.793699. Epub 2013 May 3.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Autoimmunity
  • Base Sequence
  • CTLA-4 Antigen / antagonists & inhibitors
  • CTLA-4 Antigen / genetics*
  • Case-Control Studies
  • Clinical Trials, Phase II as Topic
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Humans
  • Ipilimumab
  • Kaplan-Meier Estimate
  • Male
  • Melanoma / drug therapy
  • Melanoma / genetics*
  • Melanoma / mortality
  • Melanoma / secondary
  • Middle Aged
  • Multicenter Studies as Topic
  • Pilot Projects
  • Polymorphism, Single Nucleotide*
  • Sequence Analysis, DNA
  • Skin Neoplasms / drug therapy
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / mortality
  • Skin Neoplasms / pathology
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • CTLA-4 Antigen
  • Ipilimumab