Toll-like Receptor 4 Gene Polymorphisms and Susceptibility to Colorectal Cancer: a Meta-analysis and Review

Overview

Journal Arch Med Sci

Specialty General Medicine

Date 2015 Sep 1

PMID 26322080

Citations 14

Authors

Wang Yan Sheng

Zhang Yong

Zhu Yun

Hu Hong

Luo Lin Hai

Affiliations

Soon will be listed here.

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.

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References

Ferwerda B, McCall M, Verheijen K, Kullberg B, van der Ven A, Van der Meer J . Functional consequences of toll-like receptor 4 polymorphisms. Mol Med. 2008; 14(5-6):346-52. PMC: 2215765. DOI: 10.2119/2007-00135.Ferwerda. View

Torgersen M, Engedal N, Pedersen A, Husebye H, Espevik T, Sandvig K . Toll-like receptor 4 facilitates binding of Shiga toxin to colon carcinoma and primary umbilical vein endothelial cells. FEMS Immunol Med Microbiol. 2010; 61(1):63-75. DOI: 10.1111/j.1574-695X.2010.00749.x. View

Shen X, Shi R, Zhang H, Li K, Zhao Y, Zhang R . The Toll-like receptor 4 D299G and T399I polymorphisms are associated with Crohn's disease and ulcerative colitis: a meta-analysis. Digestion. 2010; 81(2):69-77. DOI: 10.1159/000260417. View

Vuononvirta J, Peltola V, Mertsola J, He Q . Risk of repeated Moraxella catarrhalis colonization is increased in children with Toll-like receptor 4 Asp299Gly polymorphism. Pediatr Infect Dis J. 2013; 32(11):1185-8. DOI: 10.1097/INF.0b013e31829e6df2. View

Zhu L, Yuan H, Jiang T, Wang R, Ma H, Zhang S . Association of TLR2 and TLR4 polymorphisms with risk of cancer: a meta-analysis. PLoS One. 2013; 8(12):e82858. PMC: 3869723. DOI: 10.1371/journal.pone.0082858. View

Chang G, Hu C, Eng C, Skibber J, Rodriguez-Bigas M . Practical application of a calculator for conditional survival in colon cancer. J Clin Oncol. 2009; 27(35):5938-43. PMC: 6669907. DOI: 10.1200/JCO.2009.23.1860. View

Kawai T, Akira S . Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011; 34(5):637-50. DOI: 10.1016/j.immuni.2011.05.006. View

Kawai T, Akira S . TLR signaling. Cell Death Differ. 2006; 13(5):816-25. DOI: 10.1038/sj.cdd.4401850. View

Oblak A, Jerala R . Toll-like receptor 4 activation in cancer progression and therapy. Clin Dev Immunol. 2011; 2011:609579. PMC: 3216292. DOI: 10.1155/2011/609579. View

10.

Eyking A, Ey B, Runzi M, Roig A, Reis H, Schmid K . Toll-like receptor 4 variant D299G induces features of neoplastic progression in Caco-2 intestinal cells and is associated with advanced human colon cancer. Gastroenterology. 2011; 141(6):2154-65. PMC: 3268964. DOI: 10.1053/j.gastro.2011.08.043. View

11.

Liu F, Lu W, Qian Q, Qi W, Hu J, Feng B . Frequency of TLR 2, 4, and 9 gene polymorphisms in Chinese population and their susceptibility to type 2 diabetes and coronary artery disease. J Biomed Biotechnol. 2012; 2012:373945. PMC: 3469311. DOI: 10.1155/2012/373945. View

12.

Liadaki K, Petinaki E, Skoulakis C, Tsirevelou P, Klapsa D, Germenis A . Toll-like receptor 4 gene (TLR4), but not TLR2, polymorphisms modify the risk of tonsillar disease due to Streptococcus pyogenes and Haemophilus influenzae. Clin Vaccine Immunol. 2010; 18(2):217-22. PMC: 3067360. DOI: 10.1128/CVI.00460-10. View

13.

Guo J, Loke J, Zheng F, Hong F, Yea S, Fukata M . Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses. Hepatology. 2008; 49(3):960-8. PMC: 2891538. DOI: 10.1002/hep.22697. View

14.

Pages F, Galon J, Fridman W . The essential role of the in situ immune reaction in human colorectal cancer. J Leukoc Biol. 2008; 84(4):981-7. DOI: 10.1189/jlb.1107773. View

15.

Abreu M . Toll-like receptor signalling in the intestinal epithelium: how bacterial recognition shapes intestinal function. Nat Rev Immunol. 2010; 10(2):131-44. DOI: 10.1038/nri2707. View

16.

Boraska Jelavic T, Barisic M, Drmic Hofman I, Boraska V, Vrdoljak E, Peruzovic M . Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer. Clin Genet. 2006; 70(2):156-60. DOI: 10.1111/j.1399-0004.2006.00651.x. View

17.

Wang E, Qian Z, Nakasono M, Tanahashi T, Yoshimoto K, Bando Y . High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer. Br J Cancer. 2010; 102(5):908-15. PMC: 2833250. DOI: 10.1038/sj.bjc.6605558. View

18.

Guo Q, Zhu J, Xia B . Polymorphism of CD14 gene but not the mutation of TLR4 gene is associated with colorectal cancer in Chinese patients. J Gastroenterol Hepatol. 2006; 21(1 Pt 1):92-7. DOI: 10.1111/j.1440-1746.2005.04156.x. View

19.

Landi S, Gemignani F, Bottari F, Gioia-Patricola L, Guino E, Cambray M . Polymorphisms within inflammatory genes and colorectal cancer. J Negat Results Biomed. 2006; 5:15. PMC: 1634873. DOI: 10.1186/1477-5751-5-15. View

20.

Salanti G, Amountza G, Ntzani E, Ioannidis J . Hardy-Weinberg equilibrium in genetic association studies: an empirical evaluation of reporting, deviations, and power. Eur J Hum Genet. 2005; 13(7):840-8. DOI: 10.1038/sj.ejhg.5201410. View