Pooled analysis of association between a genetic variant in the 3'-untranslated region of Toll-like receptor 4 and cancer risk

Abstract

ABSTRACT. Many epidemiological studies have shown the association between certain genetic variations in the Toll-like receptor 4 (TLR4) gene (for example, rs4986790 and rs4986791) and cancer risk. However, the results from investigations into the association between rs11536889, a genetic variant in the 3'-untranslated region of TLR4, and cancer risk lack consensus. We performed a meta-analysis to investigate the effect of rs11536889 on cancer risk. A total of 12 relevant case-control studies were included in this analysis (6222 cases and 7948 controls). The pooled ORs with their corresponding 95%CIs were estimated. We did not detect any association between rs11536889 and overall cancer risk (P = 0.13). However, stratification analysis by cancer type revealed a borderline statistically significant increased risk in both genotype comparison (OR for the variant genotype in the dominant model = 1.17; 95%CI = 0.98-1.40; P = 0.08) and allele comparison (OR for variant allele = 1.14; 95%CI = 0.99-1.32; P = 0.07) for prostate cancer. In contrast, no statistically significant or borderline result was found for gastric cancer. These findings indicate that rs11536889 in TLR4 might be specifically associated with prostate 17848 X. Wang et al.©FUNPEC-RP www.funpecrp.com.br Genetics and Molecular Research 14 (4): 17847-17855 (2015) cancer. However, owing to the modest and underpowered results, and the limitations of the original studies included for analysis, further prospective studies with larger sample sizes are required to confirm our findings.

Common variants in toll-like receptor family genes and risk of gastric cancer: a systematic review and meta-analysis

“…Confirming our results, the significant relation of TLR-4 rs4986790 and TLR-4 rs4986791 variations to GC has been proposed by another meta-analysis ( Zhou et al, 2014 ). Moreover, similar to our study, two previous meta-analyses by Wang X. et al (2015) and Chen et al (2013) did not find a significant relationship between TLR-4 rs11536889 and GC. The present study is the first meta-analysis showing a significant relationship between TLR-5 rs5744174 and TLR-9 rs187084 and genetic susceptibility to GC.…”

TLR4 and MMP2 polymorphisms and their associations with cardiovascular risk factors in susceptibility to aortic aneurysmal diseases

“…Moreover, Sun et al demonstrated that TLR4 rs11536889 was a novel genetic factor in the development of coronary artery disease, influencing its angiographic extent and severity [27], while Xu et al. found that rs1927914 was correlated with susceptibility to diabetes and diabetic retinopathy in a Chinese Han population [24]. In our study, after adjusting the potential confounders, there were no associations of TLR4rs11536889 and rs1927914 polymorphisms with the risk of AA or its subtypes in the overall analysis.…”

“…In addition, the rs1927914 SNP, located in the promoter of TLR4, can influence transcriptional factor binding site, modify the promoter activity and regulate gene expression or signaling pathway [22,23]. Recently, several studies have reported that TLR4rs11536889 and rs1927914 polymorphisms had impacts on human inflammatory and malignant diseases [24–26]. Moreover, Sun et al demonstrated that TLR4 rs11536889 was a novel genetic factor in the development of coronary artery disease, influencing its angiographic extent and severity [27], while Xu et al.…”

The interaction effects between TLR4 and MMP9 gene polymorphisms contribute to aortic aneurysm risk in a Chinese Han population

“…SNP rs1927914 locates in the 5′-UTR of TLR4 and may influence transcriptional factor binding site and regulate the promoter activity [14]. TLR4rs11536889 and rs1927914 polymorphisms have been reported to be correlated with various inflammatory diseases [29–31]. Furthermore, SNP rs17576 is a coding variant in exon 6 of MMP9 leading to an amino acid substitution, which might increase the enzyme activity of MMP9 [32].…”