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BMC Cancer
Published in: BMC Cancer 1/2012

Open Access 01-12-2012 | Research article

The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility

Authors: Xie Junjie, Jiang Songyao, Shi Minmin, Song Yanyan, Shen Baiyong, Deng Xiaxing, Jin Jiabin, Zhan Xi, Chen Hao

Published in: BMC Cancer | Issue 1/2012

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Abstract

Background

Toll-like receptors (TLR) are key innate immunity receptors participating in an immune response. Growing evidence suggests that mutations of TLR2/TLR9 gene are associated with the progress of cancers. The present study aimed to investigate the temporal relationship of single nucleotide polymorphisms (SNP) of TLR2/TLR9 and the risk of hepatocellular carcinoma (HCC).

Methods

In this single center-based case-control study, SNaPshot method was used to genotype sequence variants of TLR2 and TLR9 in 211 patients with HCC and 232 subjects as controls.

Results

Two synonymous SNPs in the exon of TLR2 were closely associated with risk of HCC. Compared with those carrying wild-type homozygous genotypes (T/T), risk of HCC decreased significantly in individuals carrying the heterozygous genotypes (C/T) of the rs3804099 (adjusted odds ratio (OR), 0.493, 95% CI 0.331 - 0.736, P < 0.01) and rs3804100 (adjusted OR, 0.509, 95% CI 0.342 - 0.759, P < 0.01). There was no significant association found in two TLR9 SNPs concerning the risk of HCC. The haplotype TT for TLR2 was associated significantly with the decreased risk of HCC (OR 0.524, 95% CI 0.394 - 0.697, P = 0.000). Inversely, the risk of HCC increased significantly in patients with the haplotype CC (OR 2.743, 95% CI 1.915 - 3.930, P = 0.000).

Conclusions

These results suggested that TLR2 rs3804099 C/T and rs3804100 C/T polymorphisms were closely associated with HCC. In addition, the haplotypes composed of these two TLR2 synonymous SNPs have stronger effects on the susceptibility of HCC.
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Literature
1.
Andreakos E, Foxwell B, Feldmann M: Is targeting Toll-like receptors and their signaling pathway a useful therapeutic approach to modulating cytokine-driven inflammation?. Immunol Rev. 2004, 202: 250-265. 10.1111/j.0105-2896.2004.00202.x.CrossRefPubMed
2.
Yoshioka T, Morimoto Y, Iwagaki H, Itoh H, Saito S, Kobayashi N, Yagi T, Tanaka N: Bacterial lipopolysaccharide induces transforming growth factor beta and hepatocyte growth factor through toll-like receptor 2 in cultured human colon cancer cells. J Int Med Res. 2001, 29: 409-420.CrossRefPubMed
3.
Huang B, Zhao J, Shen S, Li H, He KL, Shen GX, Mayer L, Unkeless J, Li D, Yuan Y, Zhang GM, Xiong H, Feng ZH: Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling. Cancer Res. 2007, 67: 4346-4352. 10.1158/0008-5472.CAN-06-4067.CrossRefPubMed
4.
Testro AG, Visvanathan K: Toll-like receptors and their role in gastrointestinal disease. J Gastroenterol Hepatol. 2009, 24: 943-954. 10.1111/j.1440-1746.2009.05854.x.CrossRefPubMed
5.
French SW, Oliva J, French BA, Li J, Bardag-Gorce F: Alcohol, nutrition and liver cancer: role of Toll-like receptor signaling. World J Gastroenterol. 2010, 16: 1344-1348. 10.3748/wjg.v16.i11.1344.CrossRefPubMedPubMedCentral
6.
Thompson AJ, Colledge D, Rodgers S, Wilson R, Revill P, Desmond P, Mansell A, Visvanathan K, Locarnini S: Stimulation of the interleukin-1 receptor and Toll-like receptor 2 inhibits hepatitis B virus replication in hepatoma cell lines in vitro. Antivir Ther. 2009, 14: 797-808. 10.3851/IMP1294.CrossRefPubMed
7.
Oliva J, Bardag-Gorce F, French BA, Li J, McPhaul L, Amidi F, Dedes J, Habibi A, Nguyen S, French SW: Fat10 is an epigenetic marker for liver preneoplasia in a drug-primed mouse model of tumorigenesis. Exp Mol Pathol. 2008, 84: 102-112. 10.1016/j.yexmp.2007.12.003.CrossRefPubMedPubMedCentral
8.
Liu X, Xu Q, Chen W, Cao H, Zheng R, Li G: Hepatitis B virus DNA-induced carcinogenesis of human normal liver cells by virtue of nonmethylated CpG DNA. Oncol Rep. 2009, 21: 941-947.CrossRefPubMed
9.
Tanaka J, Sugimoto K, Shiraki K, Tameda M, Kusagawa S, Nojiri K, Beppu T, Yoneda K, Yamamoto N, Uchida K, Kojima T, Takei Y: Functional cell surface expression of toll-like receptor 9 promotes cell proliferation and survival in human hepatocellular carcinomas. Int J Oncol. 2010, 37: 805-814.PubMed
10.
Xu N, Yao HP, Sun Z, Chen Z: Toll-like receptor 7 and 9 expression in peripheral blood mononuclear cells from patients with chronic hepatitis B and related hepatocellular carcinoma. Acta Pharmacol Sin. 2008, 29: 239-244. 10.1111/j.1745-7254.2008.00711.x.CrossRefPubMed
11.
Srivastava K, Srivastava A, Kumar A, Mittal B: Gallbladder cancer predisposition: a multigenic approach to DNA-repair, apoptotic and inflammatory pathway genes. PLoS One. 2011, 6: e16449-10.1371/journal.pone.0016449.CrossRefPubMedPubMedCentral
12.
Pandey S, Mittal RD, Srivastava M, Srivastava K, Singh S, Srivastava S, Mittal B: Impact of Toll-like receptors [TLR] 2 (-196 to -174 del) and TLR 4 (Asp299Gly, Thr399Ile) in cervical cancer susceptibility in North Indian women. Gynecol Oncol. 2009, 114: 501-505. 10.1016/j.ygyno.2009.05.032.CrossRefPubMed
13.
Purdue MP, Lan Q, Wang SS, Kricker A, Menashe I, Zheng TZ, Hartge P, Grulich AE, Zhang Y, Morton LM, Vajdic CM, Holford TR, Severson RK, Leaderer BP, Cerhan JR, Yeager M, Cozen W, Jacobs K, Davis S, Rothman N, Chanock SJ, Chatterjee N, Armstrong BK: A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis. 2009, 30: 275-281.CrossRefPubMed
14.
Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J, Scott RJ: Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk. BMC Cancer. 2010, 10: 382-10.1186/1471-2407-10-382.CrossRefPubMedPubMedCentral
15.
16.
Minmin S, Xiaoqian X, Hao C, Baiyong S, Xiaxing D, Junjie X, Xi Z, Jianquan Z, Songyao J: Single nucleotide polymorphisms of toll-like receptor 4 decrease the risk of development of hepatocellular carcinoma. PLoS One. 2011, 6: e19466-10.1371/journal.pone.0019466.CrossRefPubMedPubMedCentral
17.
Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N: Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004, 96: 434-442. 10.1093/jnci/djh075.CrossRefPubMed
18.
Boraska Jelavić T, Barisić M, Drmic Hofman I, Boraska V, Vrdoljak E, Peruzović M, Hozo I, Puljiz Z, Terzić J: Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer. Clin Genet. 2006, 70: 156-160. 10.1111/j.1399-0004.2006.00651.x.CrossRefPubMed
19.
Srivastava K, Srivastava A, Kumar A, Mittal B: Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int. 2010, 30: 1067-1072. 10.1111/j.1478-3231.2010.02268.x.CrossRefPubMed
20.
Nischalke HD, Coenen M, Berger C, Aldenhoff K, Müller T, Berg T, Krämer B, Körner C, Odenthal M, Schulze F, Grünhage F, Nattermann J, Sauerbruch T, Spengler U: The toll-like receptor 2 (TLR2) -196 to -174 del/ins polymorphism affects viral loads and susceptibility to hepatocellular carcinoma in chronic hepatitis C. Int J Cancer. 2011, doi:10.1002/ijc.26143,
21.
Egan MF, Straub RE, Goldberg TE, Yakub I, Callicott JH, Hariri AR, Mattay VS, Bertolino A, Hyde TM, Shannon-Weickert C, Akil M, Crook J, Vakkalanka RK, Balkissoon R, Gibbs RA, Kleinman JE, Weinberger DR: Variation in GRM3 affects cognition, prefrontal glutamate, and risk for schizophrenia. Proc Natl Acad Sci USA. 2004, 101: 12604-12609. 10.1073/pnas.0405077101.CrossRefPubMedPubMedCentral
22.
Fedetz M, Matesanz F, Caro-Maldonado A, Fernandez O, Tamayo JA, Guerrero M, Delgado C, López-Guerrero JA, Alcina A: OAS1 gene haplotype confers susceptibility to multiple sclerosis. Tissue Antigens. 2006, 68: 446-449. 10.1111/j.1399-0039.2006.00694.x.CrossRefPubMed
23.
Solís-Añez E, Delgado-Luengo W, Borjas-Fuentes L, Zabala W, Arráiz N, Pineda L, Portillo MG, González-Ferrer S, Chacín JA, Peña J, Montiel C, Morales A, Rojas de Atencio A, Cañizales J, González R, Miranda LE, Abreu N, Delgado J: Molecular analysis of the GABRB3 gene in autistic patients: an exploratory study. Invest Clin. 2007, 48: 225-242.PubMed
24.
Hunt R, Sauna ZE, Ambudkar SV, Gottesman MM, Kimchi-Sarfaty C: Silent (synonymous) SNPs: should we care about them?. Methods Mol Biol. 2009, 578: 23-39. 10.1007/978-1-60327-411-1_2.CrossRefPubMed
25.
Shen LX, Basilion JP, Stanton VP: Single-nucleotide polymorphisms can cause different structural folds of mRNA. Proc Natl Acad Sci USA. 1999, 96: 7871-7876. 10.1073/pnas.96.14.7871.CrossRefPubMedPubMedCentral
26.
Cartegni L, Chew SL, Krainer AR: Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet. 2002, 3: 285-298. 10.1038/nrg775.CrossRefPubMed
27.
Chamary JV, Parmley JL, Hurst LD: Hearing silence: non-neutral evolution at synonymous sites in mammals. Nat Rev Genet. 2006, 7: 98-108. 10.1038/nrg1770.CrossRefPubMed
28.
Diatchenko L, Slade GD, Nackley AG, Bhalang K, Sigurdsson A, Belfer I, Goldman D, Xu K, Shabalina SA, Shagin D, Max MB, Makarov SS, Maixner W: Genetic basis for individual variations in pain perception and the development of a chronic pain condition. Hum Mol Genet. 2005, 14: 135-143.CrossRefPubMed
29.
Etokebe GE, Knezević J, Petricević B, Pavelić J, Vrbanec D, Dembić Z: Single-nucleotide polymorphisms in genes encoding toll-like receptor -2, -3, -4, and -9 in case-control study with breast cancer. Genet Test Mol Biomarkers. 2009, 13: 729-734. 10.1089/gtmb.2009.0045.CrossRefPubMed
30.
Hold GL, Smith MG, McLean MH, Berry S, McColl KE, Mowat A, El Omar EM: Innate immune response gene polymorphisms and their role in H-pylori-induced gastric cancer. Gastroenterology. 2006, 130: A61-CrossRef
31.
Hold GL, Rabkin CS, Gammon MD, Berry SH, Smith MG, Lissowska J, Risch HA, Chow WH, Mowat NA, Vaughan TL, El-Omar EM: CD14-159C/T and TLR9-1237T/C polymorphisms are not associated with gastric cancer risk in Caucasian populations. Eur J Cancer Prev. 2009, 18: 117-119. 10.1097/CEJ.0b013e3283101292.CrossRefPubMedPubMedCentral
32.
Zhang H, Zhai Y, Hu Z, Wu C, Qian J, Jia W, Ma F, Huang W, Yu L, Yue W, Wang Z, Li P, Zhang Y, Liang R, Wei Z, Cui Y, Xie W, Cai M, Yu X, Yuan Y, Xia X, Zhang X, Yang H, Qiu W, Yang J, Gong F, Chen M, Shen H, Lin D, Zeng YX, He F, Zhou G: Genome-wide association study identifies 1p36.22 as a new susceptibility locus for hepatocellular carcinoma in chronic hepatitis B virus carriers. Nat Genet. 2010, 42: 755-758. 10.1038/ng.638.CrossRefPubMed
Metadata
Title
The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility
Authors
Xie Junjie
Jiang Songyao
Shi Minmin
Song Yanyan
Shen Baiyong
Deng Xiaxing
Jin Jiabin
Zhan Xi
Chen Hao
Publication date
01-12-2012
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2012
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-12-57

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