Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and cancer risk

A meta-analysis

Authors

  • Yonggang Zhang MD,

    1. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
    2. West China Medical School, Sichuan University, Chengdu, Sichuan, China
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  • Jie Zhang MD,

    1. Key Laboratory of Laboratory Medicine, Ministry of Education, Zhejiang Provincial Key Laboratory of Medical Genetics, Wenzhou Medical College, Wenzhou, Zhejiang, China
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    • The first 3 authors contributed equally to this article.

  • Yao Deng MD,

    1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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  • Can Tian MD,

    1. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
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  • Xiaobo Li MD,

    1. Department of Respiratory Medicine, The 45second Military Hospital of China, Chengdu, Sichuan, China
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  • Jin Huang MD,

    Corresponding author
    1. West China Medical School, Sichuan University, Chengdu, Sichuan, China
    • West China Medical School, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan 610041, China
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    • Fax: (011) 28-85421102

  • Hong Fan MD, PhD

    Corresponding author
    1. Department of Respiratory Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan, China
    2. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, China
    • Department of Respiratory Medicine, Department of Laboratory Medicine, West China Hospital, Sichuan University, Guoxuexiang 37, Chengdu, Sichuan 610041, China
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    • Fax: (011) 86-28-85423520


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. Cancer 2011;. © 2011 American Cancer Society.

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