Toll-like receptor 4 gene polymorphisms and susceptibility to colorectal cancer: a meta-analysis and review

Abstract

Introduction: Many case-control studies have investigated the association between toll-like receptor 4 (TLR4) Asp299Gly and Thr399Ile polymorphisms and risk of colorectal cancer (CRC). However, published data are still conflicting.

Material and methods: A systematic search was conducted in the electronic databases of PubMed, MEDLINE, EMBASE, Web of Science and CNKI between 2000 and 2014. The associations between TLR4 polymorphisms and CRC susceptibility were assessed by pooled odds ratios (ORs) and 95% confidence intervals (95% CI) in fixed or random effects models.

Results: In total nine case-control studies were identified in this meta-analysis. For TLR4 Asp299Gly polymorphism, 9 studies included 1198 cases and 1290 controls. The GG genotype carriers had higher risk for developing CRC than AA + GA genotype carriers (OR = 1.95, 95% CI: 1.00-3.77, p = 0.05). No association was found in other genetic models (p > 0.05). Analysis stratified by ethnicity showed no association in any genetic models among the Asian or Caucasian population. For TLR4 Thr399Ile polymorphism, 6 studies contained 619 cases and 632 controls. The overall analysis showed significantly increased risk in TT homozygote carriers compared to CC homozygote (OR = 4.99, 95% CI: 1.41-17.65, p = 0.01) and C carriers (TC + CC) (OR = 4.50, 95% CI: 1.27-15.87, p = 0.02). In terms of analyses stratified by race, a significant association was found in each genetic model among the Asian population, rather than the Caucasian group.

Conclusions: The GG homozygote carriers of TLR4 Asp299Gly and TT homozygote carriers of TLR4 Thr399Ile polymorphisms might be correlated with an increased risk of CRC, suggesting they may serve as genetic risk factors for CRC.

Keywords: colorectal carcinoma; meta-analysis; polymorphism; toll-like receptor 4.

Figure 1

Flow chart of literature screening

Figure 2

Forest plot of odds ratios (ORs) of TLR4 Asp299Gly polymorphism (GG vs. GA + AA) associated with CRC stratified by ethnicity

Figure 3

Forest plot of odds ratios (ORs) of TLR4 Thr399Ile polymorphism (TT vs. CC) associated with CRC risk

Figure 4

Meta-analysis of TLR4 Thr399Ile polymorphism (TT vs. TC + CC) with risk of CRC

Figure 5

Forest plot of CRC associated with distribution of TLR4 Thr399Ile polymorphism (TT + TC vs. CC) by stratified analysis

Figure 6

Association between T allele of TLR4 Thr399Ile polymorphism and CRC risk

Figure 7

Begg's funnel plot for publication bias in selection of studies