Association between the Cytotoxic T-Lymphocyte Antigen 4 49G > A polymorphism and cancer risk: a meta-analysisReportar como inadecuado

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BMC Cancer

, 10:522

Genetics, genomics and epigenetics


BackgroundAs a key gene in the immunosurveillance of cell malignancy, Cytotoxic T-lymphocyte antigen 4 CTLA-4 is an important negative regulator of T cell activation and proliferation. The CTLA-4 +49G > A polymorphism is one of the most commonly studied polymorphisms in this gene due to its association with cancer risks, but previous results have been conflicting.

MethodsWe preformed a meta-analysis using 22 eligible case-control studies including 32 datasets with a total of 11,273 patients and 13,179 controls to summarize the existing data on the association between the CTLA-4 +49G > A polymorphism and cancer risk.

ResultsCompared with the common CTLA-4 +49G > A GG genotype, the carriers of variant genotypes CTLA-4 +49 GC-CC had a 1.24-fold elevated risk of cancer 95% CI = 1.18-1.32, P < 0.05 under the dominant genetic model, as estimated using a fixed effect model. The effect of the CTLA-4 +49G > A polymorphism was further evaluated using stratification analysis. In four breast cancer studies, patients with the variant genotypes had a significantly increased risk of breast cancer OR = 1.31, 95% CI = 1.17-1.48, P < 0.00001. A similar result was found in three skin cancer studies OR = 1.30, 95% CI = 1.10-1.52, P = 0.001. In 26 solid tumor studies, subjects with the variant genotypes had a significantly higher risk of developing solid tumors OR = 1.25, 95% CI = 1.18-1.33, P < 0.00001 compared with the 6 non-solid tumor studies OR = 1.08, 95% CI = 0.79-1.48, P = 0.62. Patients with variant genotypes had significantly increased risk of non-epithelial tumors and epithelial tumors, with ORs of 1.23 95% CI = 1.14-1.32, P < 0.00001 and 1.29 95% CI = 1.17-1.41, P < 0.00001, respectively. It was also demonstrated that the increased risk of cancer associated with CTLA-4 +49G > A variant genotypes was more pronounced in Caucasians OR = 1.29, 95% CI = 1.13-1.47, P = 0.0002, Asians OR = 1.23, 95% CI = 1.16-1.32, P < 0.00001 and Chinese OR = 1.23, 95% CI = 1.15-1.31, P < 0.00001.

ConclusionOur meta-analysis suggests that the CTLA-4 +49G > A polymorphism genotypes GA + AA might be associated with an increased risk of cancer, especially in Caucasians and Chinese.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-10-522 contains supplementary material, which is available to authorized users.

Jian Zheng, Xiao Yu contributed equally to this work.

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Autor: Jian Zheng - Xiao Yu - Lan Jiang - Mang Xiao - Bing Bai - Jiachun Lu - Yifeng Zhou


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