Dataset Information

Current evidence on the cytotoxic T-lymphocyte antigen 4 + 49G > A polymorphism and digestive system cancer risks: a meta-analysis involving 11,923 subjects.

ABSTRACT: Cytotoxic T-lymphocyte antigen (CTLA-4) plays an important role in downregulating 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 many cancer types, but the association between CTLA-4 + 49G > A polymorphism and digestive system cancer risks remain inconclusive. An updated meta-analysis based on 17 independent case-control studies consisting of 5176 cancer patients and 6747 controls was performed to address this association. Overall, there was no statistically increased risk of digestive system cancers in every genetic comparison. In subgroup analysis, this polymorphism was significantly linked to higher risks for pancreatic cancer (GG vs. AA, OR = 1.976, 95% CI = 1.496-2.611; GA vs. AA, OR = 1.433, 95% CI = 1.093-1.879; GG/GA vs. AA, OR = 1.668, 95% CI = 1.286-2.164; GG vs. GA/AA, OR = 1.502, 95% CI = 1.098-2.054; G vs. A, OR = 1.394, 95% CI = 1.098-1.770). We also observed increased susceptibility of hepatocellular cell carcinoma in homozygote comparison (OR = 1.433, 95% CI = 1.100-1.866) and dominant model (OR = 1.360, 95% CI = 1.059-1.746). According to the source of controls, significant effects were only observed in hospital-based studies (GA/AA vs. GG, OR = 1.257, 95% CI = 1.129-1.399). In the stratified analysis by ethnicity, no significantly increased risks were found in either Asian or Caucasian. Our findings suggest that the CTLA-4 + 49G > A polymorphism may be associated with the risk of pancreatic cancer and hepatocellular cell carcinoma.

SUBMITTER: Xiaolei L

PROVIDER: S-EPMC4634354 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature

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Current evidence on the cytotoxic T-lymphocyte antigen 4 + 49G > A polymorphism and digestive system cancer risks: a meta-analysis involving 11,923 subjects.

Xiaolei Liu L Baohong Yang Y Haipeng Ren R Shuzhen Liu L Jianfeng Gao G Xiangpo Pan P Haiyu Liu L Yuan Yu Y Dejie Zheng Z Jinhong Yang Y Huanxin Wang W Wenhui Wang W Guohua Yu Y

Meta gene 20151022

Cytotoxic T-lymphocyte antigen (CTLA-4) plays an important role in downregulating 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 many cancer types, but the association between CTLA-4 + 49G > A polymorphism and digestive system cancer risks remain inconclusive. An updated meta-analysis based on 17 independent case-control studies consisting of 5176 cancer patients and 6747 controls w ...[more]

PMID: 26629416

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Project description:UnlabelledCommon genetic variants significantly influence complex diseases such as primary biliary cirrhosis (PBC). We recently reported an association between PBC and a single nucleotide polymorphism (rs231725) of the immunoreceptor gene cytotoxic T-lymphocyte antigen 4 (CTLA4). We hypothesized that PBC risk attributed to this polymorphism might be increased by propensity to an overly robust inflammatory response. Thus, we examined its potential interaction with the commonly studied -308AG promoter polymorphism (rs1800629) of the tumor necrosis factor (TNF) gene for which the variant TNF2A allele causes increased TNF production. The polymorphisms were genotyped in 866 PBC patients and 761 controls from independent US and Canadian registries; the effects of individual single nucleotide polymorphisms (SNPs) and their interaction on PBC risk was assessed by logistic regression. The reported association of PBC with the CTLA4 "A/A" genotype was replicated in the Canadian cohort and significant for PBC risk in the combined data (odds ratio [OR], 1.68; P = 0.0005). TNF2A allele frequency was elevated in PBC patients, but only reached borderline significance using the combined data (OR, 1.21; P = 0.042). Analysis showed that TNF2A carriage was significantly increased in CTLA4 "A/A" PBC patients compared with CTLA4 "A/A" controls (39.7% versus 16.5%, P = 0.0004); no apparent increase of TNF2A carriage was noted in CTLA4 "A/G" or "G/G" individuals. Finally, interaction under a logistic model was highly significant, as TNF2A carriage in combination with the CTLA4 "A/A" genotype was present in 6.5% of PBC patients, compared with 1.7% of controls (OR, 3.98; P < 0.0001).ConclusionTNF2A amplifies the CTLA4 rs231725 "A/A" genotype risk for PBC. Although the mechanisms remain unclear, the premise that deficiency in T-cell regulation resulting in an increased risk of PBC is amplified by overexpression of an important proinflammatory cytokine provides a basis for future functional studies.

Dataset Information

Current evidence on the cytotoxic T-lymphocyte antigen 4 + 49G > A polymorphism and digestive system cancer risks: a meta-analysis involving 11,923 subjects.

Publications

Current evidence on the cytotoxic T-lymphocyte antigen 4 + 49G > A polymorphism and digestive system cancer risks: a meta-analysis involving 11,923 subjects.

Similar Datasets

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