Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk: a meta-analysis.

Abstract

BACKGROUND:

Polymorphisms in the cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene have been implicated in susceptibility to cancer, but the many published studies have reported inconclusive results. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of cancer.

METHODS:

The PubMed and EMBASE databases were searched for all articles published up to September 19, 2010 that addressed cancer and polymorphisms, variants, or mutations of CTLA-4. A statistical analysis was performed using proprietary statistical software.

RESULTS:

Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 48 case-control studies from 27 articles were analyzed. The results indicated that individuals who carried the +49 G allele (AG + GG) had a 16% decreased risk of cancer compared with homozygotes (+49AA; odds ratio [OR], 0.84; 95% confidence interval [CI], 0.74-0.95). However, there was no significant association between the risk of cancer and the -318C/T polymorphism or the CT60 polymorphism (-318C/T: OR, 1.23; 95% CI, 0.99-1.54 for TT + TC vs CC; CT60: OR, 1.02; 95% CI, 0.80-1.29 for AA + AG vs GG). In further stratified analyses for the +49A/G and -318C/T polymorphisms, the decreased risk of cancer remained in subgroups of Europeans, patients with breast cancer, and patients with lung cancer for the +49A/G polymorphism; whereas an increased risk of cancer was observed among Europeans for the -318C/T polymorphism.

CONCLUSIONS:

Results from the current meta-analysis suggested that the +49A/G and -318C/T polymorphisms in CTLA-4 are risk factors for cancer. To further evaluate gene-gene and gene-environment interactions between CTLA-4 polymorphisms and the risk of cancer, more studies with larger groups of patients will be required.

• Authors: Yonggang Zhang, Jie Zhang, Yao Deng, Can Tian, Xiaobo Li, Jin Huang, Hong Fan
• Journal: Cancer (Cancer) Vol. 117 Issue 18 Pg. 4312-24 (Sep 15 2011) ISSN: 1097-0142 [Electronic] United States
• PMID: 21387262 (Publication Type: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 American Cancer Society.

Chemical References

• Antigens, CD
• CTLA-4 Antigen
• CTLA4 protein, human

Topics

• Antigens, CD (genetics)
• CTLA-4 Antigen
• Case-Control Studies
• Genetic Predisposition to Disease
• Humans
• Neoplasms (genetics)
• Polymorphism, Genetic
• Risk Factors