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Influence of Cytotoxic T Lymphocyte-associated Antigen 4 (CTLA4) Common Polymorphisms on Outcome in Treatment of Melanoma Patients With CTLA-4 Blockade
| Content Provider | Scilit |
|---|---|
| Author | Breunis, Willemijn B. Tarazona, Eduardo Chen, Renee Kiley, Maureen Rosenberg, Steven A. Chanock, Stephen J. |
| Copyright Year | 2008 |
| Description | Journal: Journal of Immunotherapy Blockade of the cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a down-regulator of T-cell activation, can cause cancer regression in patients with metastatic melanoma. However, not all patients respond well to the therapy and some develop severe autoimmune reactions. We hypothesized that common genetic variation in the CTLA4 gene could contribute to response to CTLA-4 blockade and the occurrence of autoimmune reactions. We investigated 7 common single nucleotide polymorphisms, SNPs, (rs733618, rs4553808, rs11571317, rs5742909, rs231775, rs3087243, and rs7565213) in 152 white melanoma patients who received CTLA-4 blockade. Three SNPs were associated with response to therapy: proximal promoter SNPs, rs4553808 [P=0.002; odds ratio (OR) 3.39; 95% confidence interval (CI), 1.62-7.10] and rs11571327 (P=0.02; OR 2.89; 95% CI, 1.23-6.83) and the nonsynonymous SNP rs231775 (Thr17Ala, P=0.009; OR 0.39; 95% CI, 0.18-0.82). A haplotype analysis including the 7 SNPs suggested that the common haplotype, TACCGGG could be associated with no response (P=0.02) whereas the haplotype TGCCAGG (P=0.06; OR 4.13; 95% CI, 1.17-14.5) could be associated with response to the treatment. No significant association was observed for occurrence of severe autoimmune reactions (grade III/IV) either by single SNP or haplotype analyses. Our results suggest that genetic variation in CTLA4 could influence response to CTLA-4 blockade therapy in metastatic melanoma patients, but further studies are necessary to confirm the observed associations. |
| Related Links | http://europepmc.org/articles/pmc3276400?pdf=render https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3276400/pdf |
| Ending Page | 590 |
| Page Count | 5 |
| Starting Page | 586 |
| ISSN | 15249557 |
| e-ISSN | 15374513 |
| DOI | 10.1097/cji.0b013e31817fd8f3 |
| Journal | Journal of Immunotherapy |
| Issue Number | 6 |
| Volume Number | 31 |
| Language | English |
| Publisher | Ovid Technologies (Wolters Kluwer Health) |
| Publisher Date | 2008-07-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Immunotherapy Single Nucleotide Polymorphism Ctla-4 Blockade |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Cancer Research Immunology Pharmacology |
