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Correlation of Asp299Gly and Thr399Ile polymorphisms in toll-like receptor 4 gene with digestive cancer risk: A meta-analysis.

ABSTRACT: The aim of this meta-analysis was to evaluate the correlation between the Asp299Gly and Thr399Ile polymorphisms in the toll-like receptor 4 (TLR4) gene and the risk of digestive cancer. A comprehensive search in PubMed, Web of Science (ISI), the China National Knowledge Infrastructure (CNKI), the Database of Chinese Scientific and Technical Periodicals (VIP) and the China Biology Medical (CBM) literature databases, including all the studies until May 25 2012, was conducted in order to investigate the abovementioned correlation. Statistical analysis was performed using STATA version 10.1. A total of 12 case-control studies were identified comprising 1,877 cancer patients and 3,181 controls for Asp299Gly polymorphism, and 8 case-control studies with 1,062 cancer patients and 1,867 controls for Thr399Ile polymorphism. Following sensitivity analysis and excluding studies that deviated from the Hardy-Weinberg equilibrium (HWE) in the controls, this meta-analysis demonstrated a significant correlation between the G allele of the Asp299Gly polymorphism and increased risk of gastric cancer in dominant [fixed-effect model (FEM): odds ratio (OR), 1.772; 95% confidence interval (CI), 1.340-2.343] and codominant (FEM: OR, 1.761, CI, 1.347-2.301) models. However, no significant correlation was detected for overall digestive and colorectal cancer. Furthermore, following the sensitivity analysis and exclusion of studies deviating from HWE in controls, no significant effect of the T allele of Thr399Ile polymorphism on overall digestive, gastric and colorectal cancer risk was demonstrated. This study suggests that the G allele of the TLR4 Asp299Gly polymorphism might be correlated with an increased risk of gastric cancer. However, this result needs to be further investigated by future studies.

SUBMITTER: Zhao X

PROVIDER: S-EPMC3956293 | biostudies-literature | 2013 Mar

REPOSITORIES: biostudies-literature

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Correlation of Asp299Gly and Thr399Ile polymorphisms in toll-like receptor 4 gene with digestive cancer risk: A meta-analysis.

Zhao Xinxin X Kang Shan S Liu Lingling L Zhang Dongfeng D

Biomedical reports 20121029 2

The aim of this meta-analysis was to evaluate the correlation between the Asp299Gly and Thr399Ile polymorphisms in the toll-like receptor 4 (TLR4) gene and the risk of digestive cancer. A comprehensive search in PubMed, Web of Science (ISI), the China National Knowledge Infrastructure (CNKI), the Database of Chinese Scientific and Technical Periodicals (VIP) and the China Biology Medical (CBM) literature databases, including all the studies until May 25 2012, was conducted in order to investigat ...[more]

PMID: 24648938

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Project description:ObjectiveDifferent studies have shown an association of TLR4 polymorphisms with susceptibility/resistance to malaria disease. In the current immunogenetic study, we assessed the TLR4 genotypes formed by the two common single nucleotide polymorphisms (SNPs) (Asp299Gly and Thr399Ile) in the co-segregate state in Baluchi Plasmodium falciparum infected and healthy populations from malaria hypoendemic areas of Iran. The study was performed to evaluate the distribution and correlation of TLR4 co-segregating genotypes in patients with mild malaria. Moreover, the frequency of these genotypes was compared with reported results from other populations in similar or contrasting malaria settings around the world.Materials and methodsIn this case control study, the presence of 2 SNPs in the TLR4 gene (Asp299Gly and Thr399Ile) were analyzed in 350 Baluchi patients with mild malaria and 350 unrelated healthy controls by using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP) techniques followed by sequencing analysis. Differences in the TLR4 co-segregate genotype frequencies among the studied group were determined by Fisher's exact test.ResultsAlthough the distribution of the two commonly co-segregating TLR4 genotypes presented a diverse and distinct pattern in the Baluchi population, no significant difference was detected between the cases and controls (p>0.05). A lower frequency of TLR4 Asp299Gly/Thr399Thr was observed in Baluchis with mild malaria compared to African populations (p< 0.05).ConclusionDifferences in the co-segregation patterns of TLR4 Asp299Gly/Thr399Ile genotypes in the Baluchi population compared to other malaria endemic populations may suggest different local evolutionary pressure on TLR4 polymorphisms by malaria in this region. The higher frequency of Asp299Gly/Thr399Ile genotypes among the Baluchi population compared with the African population (p< 0.05) which suffers from a larger number of severe cases might suggest that this genotype has a role in protecting against severe malaria. These findings are useful for further understanding the pathogenesis of severe malaria.

Dataset Information

Correlation of Asp299Gly and Thr399Ile polymorphisms in toll-like receptor 4 gene with digestive cancer risk: A meta-analysis.

Publications

Correlation of Asp299Gly and Thr399Ile polymorphisms in toll-like receptor 4 gene with digestive cancer risk: A meta-analysis.

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