Role of toll-like receptor 4 in colorectal carcinogenesis: a meta-analysis.
OBJECTIVE
This meta-analysis was performed to evaluate the role of toll-like receptor 4 (TLR-4) in colorectal carcinogenesis.


METHODS
The PubMed, CISCOM, CINAHL, Web of Science, Google Scholar, EBSCO, Cochrane Library, and CBM databases were searched from inception through November 1st, 2013 without language restrictions. Odds ratios (ORs) or standardized mean differences (SMD) with their 95% confidence intervals (CI) were calculated.


RESULTS
Fourteen case-control studies met the inclusion criteria for this meta-analysis. A total of 1,209 colorectal cancer (CRC) cases and 1,218 healthy controls were involved in this meta-analysis. Two common polymorphisms (299 A>G and 399 C>T) in the TLR-4 gene, TLR-4 mRNA and protein expression were assessed. Our meta-analysis results revealed that the TLR-4 399 C>T polymorphism might increase the risk of CRC (allele model: OR = 1.77, 95%CI = 1.32 ∼ 2.36, P<0.001; dominant model: OR = 1.83, 95%CI = 1.32 ∼ 2.52, P<0.001; respectively). However, we found no correlation between the TLR-4 299 A>G polymorphism and CRC risk (all P>0.05). A subgroup analysis by ethnicity suggested that TLR-4 genetic polymorphisms were associated with an increased risk of CRC among Asians (allele model: OR = 1.50, 95%CI = 1.19 ∼ 1.88, P = 0.001; dominant model: OR = 1.49, 95%CI = 1.16 ∼ 1.92, P = 0.002; respectively), but not among Caucasians and Africans (all P>0.05). Furthermore, our results showed that TLR-4 mRNA and protein levels in CRC patients were higher than those in healthy controls (TLR-4 mRNA: SMD = 2.51, 95%CI  = 0.98 ∼ 4.05, P = 0.001; TLR-4 protein: OR  = 4.75, 95%CI  = 1.16 ∼ 19.36, P = 0.030; respectively).


CONCLUSIONS
Our findings provide empirical evidence that TLR-4 may play an important role in colorectal carcinogenesis. Thus, TLR-4 is a promising potential biomarker for the early diagnosis of CRC.
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Xiao-Xia
XX
Li
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Gong-Ping
GP
Sun
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Jin
J
Meng
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Xin
X
Li
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Yuan-Xin
YX
Tang
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Zhen
Z
Li
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Mo-Fei
MF
Wang
Department of Gastrointestinal Surgery, the Fourth Affiliated Hospital of China Medical University, Shenyang, P.R. China.
Gao-Feng
GF
Liang
Department of Toxicology, School of Public Health, China Medical University, Shenyang, P.R. China.
Xiao-Bo
XB
Lu
D044466:Asian People / Q000235:genetics; D063646:Carcinogenesis / Q000378:metabolism*; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000453:epidemiology* / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism*; D012307:Risk Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism*
D012333:RNA, Messenger; D051197:Toll-Like Receptor 4