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Structural Genomic Variation in Other Toll-Like Receptors and Cancer

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Genomics of Pattern Recognition Receptors

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Abstract

Toll-like receptors (TLRs) constitute a family of receptors directly recognizing a wide spectrum of exogenous and endogenous ligands playing the key role in realization of innate and adaptive immune response and participating in the processes of cell proliferation, survival, apoptosis, angiogenesis, tissue remodeling, and repair. Polymorphisms in TLR genes may shift balance between pro- and anti-inflammatory cytokines, modulating the risk of infection, chronic inflammation, and cancer. According to the data represented in this chapter, polymorphisms in TLR1-TLR6-TLR10 gene cluster may be associated with meningioma, lymphoma, and breast cancer. Polymorphisms of TLR2 gene may correlate with altered risk of lymphoma, cervical cancer, breast cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, gallbladder cancer, and bladder cancer. Structural genomic variation in TLR3 gene may be associated with nasopharyngeal carcinoma, colorectal cancer, and thyroid cancer, polymorphisms of TLR5 gene may correlate with gastric cancer, and polymorphisms of TLR9 gene can be connected with gastric cancer, cervical cancer, and lymphoma. In addition, TLR7 gene polymorphisms may also be associated with lymphoma risk.

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References

  1. Nieters A, Beckmann L, Deeg E, Becker N (2006) Gene polymorphisms in Toll-like receptors, interleukin-10, and interleukin-10 receptor alpha and lymphoma risk. Genes Immun 7:615–624

    Article  PubMed  CAS  Google Scholar 

  2. Cerhan JR, Ansell SM, Fredericksen ZS, Kay NE, Liebow M, Call TG et al (2007) Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma. Blood 110:4455–4463

    Article  PubMed  CAS  Google Scholar 

  3. Purdue MP, Lan Q, Wang SS, Kricker A, Menashe I, Zheng TZ et al (2009) A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma. Carcinogenesis 30:275–281

    Article  PubMed  CAS  Google Scholar 

  4. Zhou XX, Jia WH, Shen GP, Qin HD, Yu XJ, Chen LZ et al (2006) Sequence variants in toll-like receptor 10 are associated with nasopharyngeal carcinoma risk. Cancer Epidemiol Biomark Prev 15:862–866

    Article  CAS  Google Scholar 

  5. Rajaraman P, Brenner AV, Neta G, Pfeiffer R, Wang SS, Yeager M et al (2010) Risk of meningioma and common variation in genes related to innate immunity. Cancer Epidemiol Biomark Prev 19:1356–1361

    Article  CAS  Google Scholar 

  6. Barnholtz-Sloan JS, Shetty PB, Guan X, Nyante SJ, Luo J, Brennan DJ et al (2010) FGFR2 and other loci identified in genome-wide association studies are associated with breast cancer in African-American and younger women. Carcinogenesis 31:1417–1423

    Article  PubMed  CAS  Google Scholar 

  7. Tahara T, Arisawa T, Wang F, Shibata T, Nakamura M, Sakata M et al (2007) Toll-like receptor 2–196 to 174 del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci 98:1790–1794

    Article  PubMed  CAS  Google Scholar 

  8. Hishida A, Matsuo K, Goto Y, Naito M, Wakai K, Tajima K et al (2010) No associations of Toll-like receptor 2 (TLR2) −196 to −174del polymorphism with the risk of Helicobacter pylori seropositivity, gastric atrophy, and gastric cancer in Japanese. Gastric Cancer 13:251–257

    Article  PubMed  CAS  Google Scholar 

  9. Noguchi E, Nishimura F, Fukai H, Kim J, Ichikawa K, Shibasaki M et al (2004) An association study of asthma and total serum immunoglobin E levels for Toll-like receptor polymorphisms in a Japanese population. Clin Exp Allergy 34:177–183

    Article  PubMed  CAS  Google Scholar 

  10. Smith MF Jr, Mitchell A, Li G, Ding S, Fitzmaurice AM, Ryan K et al (2003) TLR2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kB activation and chemokine expression by epithelial cells. J Biol Chem 278:33552–33560

    Google Scholar 

  11. Mbulaiteye SM, Hisada M, El-Omar EM (2009) Helicobacter Pylori associated global gastric cancer burden. Front Biosci 14:1490–1504

    Article  CAS  Google Scholar 

  12. Cavaleiro-Pinto M, Peleteiro B, Lunet N, Barros H (2010) Helicobacter pylori infection and gastric cardia cancer: systematic review and meta-analysis. Cancer Causes Control 22(3):375–387

    Article  PubMed  Google Scholar 

  13. de Oliveira JG, Silva AE (2012) Polymorphisms of the TLR2 and TLR4 genes are associated with risk of gastric cancer in a Brazilian population. World J Gastroenterol 18(11):1235–1242

    Article  PubMed  Google Scholar 

  14. Zeng HM, Pan KF, Zhang Y, Zhang L, Ma JL, Zhou T, Su HJ, Li WQ, Li JY, Gerhard M, Classen M, You WC (2011) Genetic variants of toll-like receptor 2 and 5, helicobacter pylori infection, and risk of gastric cancer and its precursors in a Chinese population. Cancer Epidemiol Biomark Prev 20(12):2594–2602

    Article  CAS  Google Scholar 

  15. Srivastava K, Srivastava A, Kumar A, Mittal B (2010) Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int 30:1067–1072

    Article  PubMed  CAS  Google Scholar 

  16. Pandey S, Mittal RD, Srivastava M, Srivastava K, Singh S, Srivastava S et al (2009) 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 114:501–505

    Article  PubMed  CAS  Google Scholar 

  17. Singh V, Srivastava N, Kapoor R, Mittal RD (2012) Single-nucleotide polymorphisms in genes encoding Toll-like Receptor −2, −3, −4, and -9 in a case-control study with bladder cancer susceptibility in a North Indian population. Arch Med Res 44(1):54–61

    Article  PubMed  Google Scholar 

  18. 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 (2012) 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 130:1470–1475

    Article  PubMed  CAS  Google Scholar 

  19. Theodoropoulos GE, Saridakis V, Karantanos T, Michalopoulos NV, Zagouri F, Kontogianni P, Lymperi M, Gazouli M, Zografos GC (2012) Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast 21:534–538

    Article  PubMed  Google Scholar 

  20. Yang ZH, Dai Q, Gu YJ, Guo QX, Gong L (2012) Cytokine and chemokine modification by Toll-like receptor polymorphisms is associated with nasopharyngeal carcinoma. Cancer Sci 103(4):653–658

    Article  PubMed  CAS  Google Scholar 

  21. Boraska Jelavić T, Barisić M, Drmic Hofman I, Boraska V, Vrdoljak E, Peruzović M et al (2006) Microsatelite GT polymorphism in the toll-like receptor 2 is associated with colorectal cancer. Clin Genet 70:156–160

    Article  PubMed  Google Scholar 

  22. Yim JJ, Ding L, Schäffer AA, Park GY, Shim YS, Holland SM (2004) A microsatellite polymorphism in intron 2 of human Toll-like receptor 2 gene: functional implications and racial differences. FEMS Immunol Med Microbiol 40:163–169

    Article  PubMed  CAS  Google Scholar 

  23. Yim JJ, Lee HW, Lee HS, Kim YW, Han SK, Shim YS et al (2006) The association between microsatellite polymorphisms in intron II of the human Toll-like receptor 2 gene and tuberculosis among Koreans. Genes Immun 7:150–155

    Article  PubMed  CAS  Google Scholar 

  24. Ashton KA, Proietto A, Otton G, Symonds I, McEvoy M, Attia J et al (2010) Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk. BMC Cancer 10:382

    Article  PubMed  Google Scholar 

  25. Pimentel-Nunes P, Teixeira AL, Pereira C, Gomes M, Brandão C, Rodrigues C, Gonçalves N, Boal-Carvalho I, Roncon-Albuquerque R Jr, Moreira-Dias L, Leite-Moreira AF, Medeiros R, Dinis-Ribeiro M (2012) Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis 45(1):63–69

    Article  PubMed  Google Scholar 

  26. Zeng HM, Pan KF, Zhang Y, Zhang L, Ma JL, Zhou T, Su HJ, Li WQ, Li JY, You WC (2011) The correlation between polymorphisms of Toll-like receptor 2 and Toll-like receptor 9 and susceptibility to gastric cancer. Zhonghua Yu Fang Yi Xue Za Zhi 45:588–592

    PubMed  CAS  Google Scholar 

  27. Junjie X, Songyao J, Minmin S, Yanyan S, Baiyong S, Xiaxing D, Jiabin J, Xi Z, Hao C (2012) The association between Toll-like receptor 2 single-nucleotide polymorphisms and hepatocellular carcinoma susceptibility. BMC Cancer 12:57

    Article  PubMed  Google Scholar 

  28. Kim MK, Park SW, Kim SK, Park HJ, Eun YG, Kwon KH, Kim J (2012) Association of toll-like receptor 2 polymorphisms with papillary thyroid cancer and clinicopathologic features in a Korean population. J Korean Med Sci 27(11):1333–1338

    Article  PubMed  CAS  Google Scholar 

  29. Etokebe GE, Knezević J, Petricević B, Pavelić J, Vrbanec D, Dembić Z (2009) Single-nucleotide polymorphisms in genes encoding toll-like receptor −2, −3, −4, and −9 in case-control study with breast cancer. Genet Test Mol Biomark 13:729–734

    Article  CAS  Google Scholar 

  30. Mollaki V, Georgiadis T, Tassidou A, Ioannou M, Daniil Z, Koutsokera A et al (2009) Polymorphisms and haplotypes in TLR9 and MYD88 are associated with the development of Hodgkin’s lymphoma: a candidate-gene association study. J Hum Genet 54:655–659

    Article  PubMed  CAS  Google Scholar 

  31. Carvalho A, Cunha C, Almeida AJ, Osório NS, Saraiva M, Teixeira-Coelho M, Pedreiro S, Torrado E, Domingues N, Gomes-Alves AG, Marques A, Lacerda JF, da Silva MG, Gomes M, Pinto AC, Torres F, Rendeiro P, Tavares P, Di Ianni M, Medeiros R, Heutink P, Bracci PM, Conde L, Ludovico P, Pedrosa J, Maciel P, Pitzurra L, Aversa F, Marques H, Paiva A, Skibola CF, Romani L, Castro AG, Rodrigues F (2012) The rs5743836 polymorphism in TLR9 confers a population-based increased risk of non-Hodgkin lymphoma. Genes Immun 13(2):197–201

    Article  PubMed  CAS  Google Scholar 

  32. Pandey S, Mittal B, Srivastava M, Singh S, Srivastava K, Lal P et al (2011) Evaluation of Toll-like receptors 3 (c.1377C/T) and 9 (G2848A) gene polymorphisms in cervical cancer susceptibility. Mol Biol Rep 38(7):4715–4721

    Article  PubMed  CAS  Google Scholar 

  33. Novak N, Yu CF, Bussmann C, Maintz L, Peng WM, Hart J et al (2007) Putative association of a TLR9 promoter polymorphism with atopic eczema. Allergy 62:766–772

    Article  PubMed  CAS  Google Scholar 

  34. Ng MT, Van’t Hof R, Crockett JC, Hope ME, Berry S, Thomson J et al (2010) Increase in NF-kappaB binding affinity of the variant C allele of the toll-like receptor 9–1237T/C polymorphism is associated with Helicobacter pylori-induced gastric disease. Infect Immun 78:1345–1352

    Article  PubMed  CAS  Google Scholar 

  35. Roszak A, Lianeri M, Sowińska A, Jagodziński PP (2012) Involvement of Toll-like Receptor 9 polymorphism in cervical cancer development. Mol Biol Rep 39:8425–8430

    Article  PubMed  CAS  Google Scholar 

  36. Chen X, Wang S, Liu L, Chen Z, Qiang F, Kan Y, Shen Y, Wu J, Shen H, Hu Z (2012) A genetic variant in the promoter region of Toll-like receptor 9 and cervical cancer susceptibility. DNA Cell Biol 31(5):766–771

    Article  PubMed  CAS  Google Scholar 

  37. Hold GL, Rabkin CS, Gammon MD, Berry SH, Smith MG, Lissowska J et al (2009) CD14-159C/T and TLR9-1237T/C polymorphisms are not associated with gastric cancer risk in Caucasian populations. Eur J Cancer Prev 18:117–119

    Article  PubMed  CAS  Google Scholar 

  38. Slattery ML, Herrick JS, Bondurant KL, Wolff RK (2012) Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J Cancer 130:2974–2980

    Article  PubMed  CAS  Google Scholar 

  39. Monroy CM, Cortes AC, Lopez MS, D’Amelio AM Jr, Etzel CJ, Younes A et al (2011) Hodgkin disease risk: role of genetic polymorphisms and gene–gene interactions in inflammation pathway genes. Mol Carcinog 50:36–46

    Article  PubMed  CAS  Google Scholar 

  40. He JF, Jia WH, Fan Q, Zhou XX, Qin HD, Shugart YY et al (2007) Genetic polymorphisms of TLR3 are associated with Nasopharyngeal carcinoma risk in Cantonese population. BMC Cancer 7:194

    Article  PubMed  Google Scholar 

  41. Schuring RP, Hamann L, Faber WR, Pahan D, Richardus JH, Schumann RR et al (2009) Polymorphism N248S in the human Toll-like receptor 1 gene is related to leprosy and leprosy reactions. J Infect Dis 199:1816–1819

    Article  PubMed  CAS  Google Scholar 

  42. Wurfel MM, Gordon AC, Holden TD, Radella F, Strout J, Kajikawa O et al (2008) Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis. Am J Respir Crit Care Med 178:710–720

    Article  PubMed  CAS  Google Scholar 

  43. Johnson CM, Lyle EA, Omueti KO, Stepensky VA, Yegin O, Alpsoy E et al (2007) Cutting edge: a common polymorphism impairs cell surface trafficking and functional responses of TLR1 but protects against leprosy. J Immunol 178:7520–7524

    PubMed  CAS  Google Scholar 

  44. Etokebe GE, Skjeldal F, Nilsen N, Rodionov D, Knezevic J, Bulat-Kardum L et al (2010) Toll-like receptor 2 (P631H) mutant impairs membrane internalization and is a dominant negative allele. Scand J Immunol 71:369–381

    Article  PubMed  CAS  Google Scholar 

  45. Merx S, Neumaier M, Wagner H, Kirschning CJ, Ahmad-Nejad P (2007) Characterization and investigation of single nucleotide polymorphisms and a novel TLR2 mutation in the human TLR2 gene. Hum Mol Genet 16:1225–1232

    Article  PubMed  CAS  Google Scholar 

  46. Ben-Ali M, Barbouche MR, Bousnina S, Chabbou A, Dellagi K (2004) Toll-like receptor 2 Arg677Trp polymorphism is associated with susceptibility to tuberculosis in Tunisian patients. Clin Diagn Lab Immunol 11:625–626

    PubMed  CAS  Google Scholar 

  47. Dhiman N, Ovsyannikova IG, Vierkant RA, Ryan JE, Pankratz VS, Jacobson RM et al (2008) Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results. Vaccine 26:1731–1736

    Article  PubMed  CAS  Google Scholar 

  48. Ranjith-Kumar CT, Miller W, Sun J, Xiong J, Santos J, Yarbrough I et al (2007) Effects of single nucleotide polymorphisms on Toll-like receptor 3 activity and expression in cultured cells. J Biol Chem 282:17696–17705

    Article  PubMed  CAS  Google Scholar 

  49. Qi R, Hoose S, Schreiter J, Sawant KV, Lamb R, Ranjith-Kumar CT et al (2010) Secretion of the human Toll-like receptor 3 ectodomain is affected by single nucleotide polymorphisms and regulated by Unc93b1. J Biol Chem 285:36635–36644

    Article  PubMed  CAS  Google Scholar 

  50. Blohmke CJ, Park J, Hirschfeld AF, Victor RE, Schneiderman J, Stefanowicz D et al (2010) TLR5 as an anti-inflammatory target and modifier gene in cystic fibrosis. J Immunol 185:7731–7738

    Article  PubMed  CAS  Google Scholar 

  51. Møller-Larsen S, Nyegaard M, Haagerup A, Vestbo J, Kruse TA, Børglum AD (2008) Association analysis identifies TLR7 and TLR8 as novel risk genes in asthma and related disorders. Thorax 63:1064–1069

    Article  PubMed  Google Scholar 

  52. Oh DY, Taube S, Hamouda O, Kücherer C, Poggensee G, Jessen H et al (2008) A functional toll-like receptor 8 variant is associated with HIV disease restriction. J Infect Dis 198:701–709

    Article  PubMed  CAS  Google Scholar 

  53. Tao K, Fujii M, Tsukumo S, Maekawa Y, Kishihara K, Kimoto Y et al (2007) Genetic variations of Toll-like receptor 9 predispose to systemic lupus erythematosus in Japanese population. Ann Rheum Dis 66:905–909

    Article  PubMed  CAS  Google Scholar 

  54. Kubarenko AV, Ranjan S, Rautanen A, Mills TC, Wong S, Vannberg F et al (2010) A naturally occurring variant in human TLR9, P99L, is associated with loss of CpG oligonucleotide responsiveness. J Biol Chem 285:36486–36494

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Epidemiology, Kemerovo State Medical Academy, Voroshilova Str. 22A, Kemerovo, Russia, 650029

    Anton G. Kutikhin

  2. Siberian Branch, Res Inst Cardiovascular Diseases, Russian Academy of Medical Sciences, Sosnovy Blvd. 6, Kemerovo, Russia, 650002

    Arseniy E. Yuzhalin

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  1. Anton G. Kutikhin
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Correspondence to Anton G. Kutikhin .

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Kutikhin, A.G., Yuzhalin, A.E. (2013). Structural Genomic Variation in Other Toll-Like Receptors and Cancer. In: Genomics of Pattern Recognition Receptors. Springer, Basel. https://doi.org/10.1007/978-3-0348-0688-6_4

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