Dataset Information

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

ABSTRACT:

Purpose

CTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these polymorphisms and cancer risk.

Methods

We searched the Pubmed and Web of Science databases until October 24, 2013 to obtain relevant published studies. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) for the relationship between CTLA4 gene polymorphisms and cancer susceptibility were calculated by stata 11 software. Heterogeneity tests, sensitivity analyses and publication bias assessments were also performed in our meta-analysis.

Results

A total of 22 articles comprising 31 case-control studies concerning the CTLA-4 60G/A and CTLA-4 -1661A/G polymorphisms were included in the meta-analysis. The pooled results suggested the CTLA-4 60G/A polymorphism was significantly associated with an increased skin cancer risk (AA vs. GG: OR?=?1.32, 95%CI?=?1.09-1.59; AA vs. GA+GG: OR?=?1.26, 95%CI?=?1.07-1.48). For CTLA-4 -1661 A/G polymorphism, the results showed that the CTLA-4 -1661A/G polymorphism was significantly associated with an increased cancer risk (GA vs. AA: OR?=?1.44, 95%CI?=?1.13-1.82; GA+GG vs. AA: OR?=?1.35, 95%CI?=?1.07-1.69; G vs. A: OR?=?1.21, 95%CI?=?1.01-1.47), especially in gastric cancer, breast cancer, other cancers and in Asians population subgroups.

Conclusion

Our meta-analysis suggests that the CTLA-4 -1661A/G polymorphism is a potential factor for the susceptibility of cancer, especially in gastric cancer, breast cancer and other cancers, and the CTLA-4 60G/A polymorphism is significantly associated with increased skin cancer risk. The effect of the CTLA-4 -1661A/G polymorphism on cancer susceptibility especially exists in Asians and population based subjects.

SUBMITTER: Yan Q

PROVIDER: S-EPMC3871533 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Publications

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

Yan Qing Q Chen Pin P Lu Ailin A Zhao Peng P Gu Aihua A

PloS one 20131223 12

<h4>Purpose</h4>CTLA-4 is one of the most fundamental immunosuppressive cotykines which belongs to the immunoglobulin super-family, and is expressed mainly on activated T cells. Previous studies have reported the existence of CTLA4 60G/A and CTLA4 -1661A/G polymorphism in cancers. However, the effects remain conflicting. Hence, we performed a meta-analysis to investigate the association between these polymorphisms and cancer risk.<h4>Methods</h4>We searched the Pubmed and Web of Science database ...[more]

PMID: 24376736

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Project description:PurposeThe hypoxia-inducible factor-1 alpha (HIF1A) plays a vital role in cancer initiation and progression. Previous studies have reported the existence of HIF1A P582S and A588T missense polymorphisms in renal, urothelial and prostatic carcinomas, however the effects remain conflicting. Therefore, we performed a meta-analysis to assess the association between these sites and the susceptibility of urinary cancers.MethodsWe searched the PubMed database without limits on language until Nov 25, 2012 for studies exploring the relationship of HIF1A P582S and A588T polymorphisms and urinary cancers. Still, article search was supplemented by screening the references of retrieved studies manually. Odds ratios (OR) and 95% confidence intervals (95% CI) were calculated to evaluate the strength of the associations between the two by RevMan 5.0 software. Simultaneously, publication bias was estimated by funnel plot and Begg's test with Stata 12.1 software.ResultsOverall, 11 individual case-control studies with 5195 cases and 5786 controls for P582S polymorphism, and 9 studies with 3482 cases and 4304 controls for A588T polymorphism were respectively included in the final meta-analysis. For HIF1A P582S polymorphism, individuals with TT genotype showed 1.60 fold higher risk than the others carrying CT or CC genotypes in Caucasian population (OR?=?1.60, 95% CI?=?1.09-2.33, P(heterogeneity?)=?0.11, P?=?0.02). For HIF1A A588T polymorphism, the A allele was significantly correlated with higher urinary cancers risk in Asian population (OR?=?1.41, 95% CI?=?1.03-1.93, P(heterogeneity)?=?0.22, P?=?0.03). Still, significant associations were found for prostate cancer in the allele and dominant models (OR?=?1.46, 95% CI?=?1.01-2.12, P(heterogeneity?)=?0.49, P?=?0.04 and OR?=?1.45, 95% CI?=?1.00-2.12, P(heterogeneity)?=?0.50, P?=?0.05).ConclusionsThe current findings suggest that HIF1A P582S polymorphism correlates with urinary cancers risk in Caucasian population, while A588T polymorphism may increase the risk of urinary cancers in Asian population and prostate cancer.

Project description:Cytotoxic T lymphocyte antigen-4 (CTLA-4) has been identified as an immunosuppressive molecule involved in the negative regulation of T cells. It is highly expressed in several types of autoimmune diseases and cancers including colorectal cancer (CRC). (1) Objective: To explore the association between CTLA-4 single nucleotide polymorphisms (SNP) and risk to (CRC) in the Saudi population. (2) Methods: In this case-control study, 100 patients with CRC and 100 matched healthy controls were genotyped for three CTLA-4 SNPs: rs11571317 (-658C > T), rs231775 (+49A > G) and rs3087243 (CT60 G > A), using TaqMan assay method. Associations were evaluated using odds ratios (ORs) and 95% confidence intervals (95% CIs) for five inheritance models (co-dominant, dominant, recessive, over-dominant and log-additive). Furthermore, CTLA-4 expression levels were evaluated using quantitative real-time PCR (Q-RT-PCR) in colon cancer and adjacent colon tissues. (3) Results: Our result showed a significant association of the G allele (OR = 2.337, p < 0.0001) and GG genotype of the missense SNP +49A > G with increased risk of developing CRC in codominant (OR = 8.93, p < 0.0001) and recessive (OR = 16.32, p < 0.0001) models. Inversely, the AG genotype was significantly associated with decreased risk to CRC in the codominant model (OR = 0.23, p < 0.0001). In addition, the CT60 G > A polymorphism exhibited a strong association with a high risk of developing CRC for the AA genotype in codominant (OR = 3.323, p = 0.0053) and in allele models (OR = 1.816, p = 0.005). No significant association was found between -658C > T and CRC. The haplotype analysis showed that the G-A-G haplotype of the rs11571317, rs231775 and rs3087243 was associated with high risk for CRC (OR = 57.66; p < 0.001). The CTLA-4 mRNA gene expression was found significantly higher in tumors compared to normal adjacent colon samples (p < 0.001). (4) Conclusions: Our findings support an association between the CTLA-4 rs231775 (+49A > G) and rs3087243 (CT60 G > A) polymorphisms and CRC risk in the Saudi population. Further validation in a larger cohort size is needed prior to utilizing these SNPs as a potential screening marker in the Saudi population.

Dataset Information

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

Purpose

Methods

Results

Conclusion

Publications

Association between CTLA-4 60G/A and -1661A/G polymorphisms and the risk of cancers: a meta-analysis.

Similar Datasets

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