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Association between Toll-like receptor 4 and interleukin 17 gene polymorphisms and colorectal cancer susceptibility in Northeast China

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Abstract

Limited studies about the effects of TLR 4 and IL17 polymorphisms (SNPs) on the risk of colorectal cancer (CRC) have yielded inconsistent results. Totally, 601 CRC patients and 627 controls were enrolled. Unconditional logistic regression was used to estimate the association between tagSNPs and susceptibility of CRC and the interactions effects of gene and environment on the risk of CRC. IL17 rs6973569 AG and AG/AA genotypes significantly decreased the risk of CRC compared with GG genotype (ORadjusted = 0.72, 95 % CI 0.55–0.94 and ORadjusted = 0.74, 95 % CI 0.57–0.97). The haplotype G–T–G–C–A–G accounting for the largest proportion haplotypes increased the risk of CRC (OR = 1.27, 95 % CI 1.06–1.53). However, G–C–C–T–A–G and G–C–G–C–A–G haplotypes decreased the susceptibility of CRC. Synergistic interactions between TLR 4 rs1927911 CT/TT and higher pungent food intake as well as IL17 rs6973569 AG/AA genotypes and higher intake of sausage food (ORi=1.72, 95 % CI 1.04–2.84 and ORi=3.38, 95 % CI 1.28–8.91) on the risk of CRC were observed. IL17 rs6973569 SNP might be an independent factor of susceptibility to CRC. TLR 4 haplotype of G–T–G–C–A–G may increase risk of CRC. Higher intake of pungent and sausage food synergistically interacted with TLR 4 and IL17 SNPs on the risk of CRC.

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References

  1. http://globocan.iarc.fr/Pages/fact_sheets_cancer.aspx.

  2. Sung JJ, Lau JY, Goh KL, Leung WK. Asia Pacific Working Group on Colorectal C. Increasing incidence of colorectal cancer in Asia: implications for screening. Lancet Oncol. 2005;6(11):871–6. doi:10.1016/S1470-2045(05)70422-8.

    Article  PubMed  Google Scholar 

  3. Landi S, Moreno V, Gioia-Patricola L, Guino E, Navarro M, de Oca J, et al. Association of common polymorphisms in inflammatory genes interleukin (IL)6, IL8, tumor necrosis factor alpha, NFKB1, and peroxisome proliferator-activated receptor gamma with colorectal cancer. Cancer Res. 2003;63(13):3560–6.

    PubMed  CAS  Google Scholar 

  4. Itzkowitz SH, Yio X. Inflammation and cancer IV. Colorectal cancer in inflammatory bowel disease: the role of inflammation. Am J Physiol Gastrointest Liver Physiol. 2004;287(1):G7–17. doi:10.1152/ajpgi.00079.2004.

    Article  PubMed  CAS  Google Scholar 

  5. Fukata M, Abreu MT. TLR4 signalling in the intestine in health and disease. Biochem Soc Trans. 2007;35(Pt 6):1473–8. doi:10.1042/BST0351473.

    Article  PubMed  CAS  Google Scholar 

  6. Knuefermann P, Nemoto S, Baumgarten G, Misra A, Sivasubramanian N, Carabello BA, et al. Cardiac inflammation and innate immunity in septic shock: is there a role for toll-like receptors? Chest. 2002;121(4):1329–36.

    Article  PubMed  CAS  Google Scholar 

  7. Machida K, Tsukamoto H, Mkrtchyan H, Duan L, Dynnyk A, Liu HM, et al. Toll-like receptor 4 mediates synergism between alcohol and HCV in hepatic oncogenesis involving stem cell marker Nanog. Proc Natl Acad Sci USA. 2009;106(5):1548–53. doi:10.1073/pnas.0807390106.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  8. Testro AG, Visvanathan K. Toll-like receptors and their role in gastrointestinal disease. J Gastroenterol Hepatol. 2009;24(6):943–54. doi:10.1111/j.1440-1746.2009.05854.x.

    Article  PubMed  CAS  Google Scholar 

  9. Aderem A, Ulevitch RJ. Toll-like receptors in the induction of the innate immune response. Nature. 2000;406(6797):782–7. doi:10.1038/35021228.

    Article  PubMed  CAS  Google Scholar 

  10. Kawaguchi M, Adachi M, Oda N, Kokubu F, Huang SK. IL-17 cytokine family. J Allergy Clin Immunol. 2004;114(6):1265–73. doi:10.1016/j.jaci.2004.10.019 quiz 74.

    Article  PubMed  CAS  Google Scholar 

  11. Kolls JK, Linden A. Interleukin-17 family members and inflammation. Immunity. 2004;21(4):467–76. doi:10.1016/j.immuni.2004.08.018.

    Article  PubMed  CAS  Google Scholar 

  12. Fukata M, Chen A, Klepper A, Krishnareddy S, Vamadevan AS, Thomas LS, et al. Cox-2 is regulated by Toll-like receptor-4 (TLR4) signaling: role in proliferation and apoptosis in the intestine. Gastroenterology. 2006;131(3):862–77. doi:10.1053/j.gastro.2006.06.017.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Gorczyca W, Gong J, Ardelt B, Traganos F, Darzynkiewicz Z. The cell cycle related differences in susceptibility of HL-60 cells to apoptosis induced by various antitumor agents. Cancer Res. 1993;53(13):3186–92.

    PubMed  CAS  Google Scholar 

  14. Zou W, Restifo NP. T(H)17 cells in tumour immunity and immunotherapy. Nat Rev Immunol. 2010;10(4):248–56. doi:10.1038/nri2742.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Abreu MT. 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.

    Article  PubMed  CAS  Google Scholar 

  16. McGovern DP, Rotter JI, Mei L, Haritunians T, Landers C, Derkowski C, et al. Genetic epistasis of IL23/IL17 pathway genes in Crohn’s disease. Inflamm Bowel Dis. 2009;15(6):883–9. doi:10.1002/ibd.20855.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Arisawa T, Tahara T, Shibata T, Nagasaka M, Nakamura M, Kamiya Y, et al. The influence of polymorphisms of interleukin-17A and interleukin-17F genes on the susceptibility to ulcerative colitis. J Clin Immunol. 2008;28(1):44–9. doi:10.1007/s10875-007-9125-8.

    Article  PubMed  CAS  Google Scholar 

  18. Hong J, Leung E, Fraser AG, Merriman TR, Vishnu P, Krissansen GW. TLR2, TLR4 and TLR9 polymorphisms and Crohn’s disease in a New Zealand Caucasian cohort. J Gastroenterol Hepatol. 2007;22(11):1760–6. doi:10.1111/j.1440-1746.2006.04727.x.

    Article  PubMed  CAS  Google Scholar 

  19. Fukata M, Chen A, Vamadevan AS, Cohen J, Breglio K, Krishnareddy S, et al. Toll-like receptor-4 promotes the development of colitis-associated colorectal tumors. Gastroenterology. 2007;133(6):1869–81. doi:10.1053/j.gastro.2007.09.008.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  20. Tsilidis KK, Helzlsouer KJ, Smith MW, Grinberg V, Hoffman-Bolton J, Clipp SL, et al. Association of common polymorphisms in IL10, and in other genes related to inflammatory response and obesity with colorectal cancer. Cancer Causes Control. 2009;20(9):1739–51. doi:10.1007/s10552-009-9427-7.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pimentel-Nunes P, Teixeira AL, Pereira C, Gomes M, Brandao C, Rodrigues C, et al. Functional polymorphisms of Toll-like receptors 2 and 4 alter the risk for colorectal carcinoma in Europeans. Dig Liver Dis. 2013;45(1):63–9. doi:10.1016/j.dld.2012.08.006.

    Article  PubMed  CAS  Google Scholar 

  22. Boraska Jelavic T, Barisic M, Drmic Hofman I, Boraska V, Vrdoljak E, Peruzovic M, et al. Microsatellite 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.

    Article  PubMed  CAS  Google Scholar 

  23. 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.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  PubMed Central  Google Scholar 

  25. Slattery ML, Herrick JS, Bondurant KL, Wolff RK. Toll-like receptor genes and their association with colon and rectal cancer development and prognosis. Int J cancer J Int Du cancer. 2012;130(12):2974–80. doi:10.1002/ijc.26314.

    Article  CAS  Google Scholar 

  26. Davoodi H, Seow HF. Variant Toll-like receptor4 (Asp299Gly and Thr399Ile alleles) and Toll-like receptor2 (Arg753Gln and Arg677Trp alleles) in colorectal cancer. Iran J Allergy Asthma Immunol. 2011;10(2):91–9. doi:10.02/ijaai.9199.

    PubMed  CAS  Google Scholar 

  27. Wang L, Jiang Y, Zhang Y, Wang Y, Huang S, Wang Z, et al. Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer. PLoS One. 2012;7(3):e34400. doi:10.1371/journal.pone.0034400.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  28. Quan Y, Zhou B, Wang Y, Duan R, Wang K, Gao Q, et al. Association between IL17 polymorphisms and risk of cervical cancer in Chinese women. Clin Dev Immunol. 2012;2012:258293. doi:10.1155/2012/258293.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Shibata T, Tahara T, Hirata I, Arisawa T. Genetic polymorphism of interleukin-17A and -17F genes in gastric carcinogenesis. Hum Immunol. 2009;70(7):547–51. doi:10.1016/j.humimm.2009.04.030.

    Article  PubMed  CAS  Google Scholar 

  30. Vasen HF, Watson P, Mecklin JP, Lynch HT. New clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome) proposed by the International Collaborative group on HNPCC. Gastroenterology. 1999;116(6):1453–6.

    Article  PubMed  CAS  Google Scholar 

  31. http://analysis.bio-x.cn/SHEsisMain.htm.

  32. Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122(1):107–18. doi:10.1016/j.cell.2005.05.007.

    Article  PubMed  CAS  Google Scholar 

  33. Song J, Kim DY, Kim CS, Kim HJ, Lee DH, Lee HM, et al. The association between Toll-like receptor 4 (TLR4) polymorphisms and the risk of prostate cancer in Korean men. Cancer Genet Cytogenet. 2009;190(2):88–92. doi:10.1016/j.cancergencyto.2008.12.011.

    Article  PubMed  CAS  Google Scholar 

  34. Wang MH, Helzlsouer KJ, Smith MW, Hoffman-Bolton JA, Clipp SL, Grinberg V, et al. Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II. Prostate. 2009;69(8):874–85. doi:10.1002/pros.20933.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  35. Chen YC, Giovannucci E, Lazarus R, Kraft P, Ketkar S, Hunter DJ. Sequence variants of toll-like receptor 4 and susceptibility to prostate cancer. Cancer Res. 2005;65(24):11771–8. doi:10.1158/0008-5472.CAN-05-2078.

    Article  PubMed  CAS  Google Scholar 

  36. Zhang K, Zhou B, Wang Y, Rao L, Zhang L. The TLR4 gene polymorphisms and susceptibility to cancer: a systematic review and meta-analysis. Eur J Cancer. 2013;49(4):946–54. doi:10.1016/j.ejca.2012.09.022.

    Article  PubMed  CAS  Google Scholar 

  37. Ghanim H, Sia CL, Upadhyay M, Korzeniewski K, Viswanathan P, Abuaysheh S, et al. Orange juice neutralizes the proinflammatory effect of a high-fat, high-carbohydrate meal and prevents endotoxin increase and Toll-like receptor expression. Am J Clin Nutr. 2010;91(4):940–9. doi:10.3945/ajcn.2009.28584.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  38. Badawi AF, El-Sohemy A, Stephen LL, Ghoshal AK, Archer MC. The effect of dietary n-3 and n-6 polyunsaturated fatty acids on the expression of cyclooxygenase 1 and 2 and levels of p21ras in rat mammary glands. Carcinogenesis. 1998;19(5):905–10.

    Article  PubMed  CAS  Google Scholar 

  39. Haas SL, Ye W, Lohr JM. Alcohol consumption and digestive tract cancer. Curr Opin Clin Nutr Metab Care. 2012;15(5):457–67. doi:10.1097/MCO.0b013e3283566699.

    Article  PubMed  CAS  Google Scholar 

  40. Ban JO, Yuk DY, Woo KS, Kim TM, Lee US, Jeong HS, et al. Inhibition of cell growth and induction of apoptosis via inactivation of NF-kappaB by a sulfurcompound isolated from garlic in human colon cancer cells. J Pharmacol Sci. 2007;104(4):374–83.

    Article  PubMed  CAS  Google Scholar 

  41. Bozinovski S, Vlahos R, Zhang Y, Lah LC, Seow HJ, Mansell A, et al. Carbonylation caused by cigarette smoke extract is associated with defective macrophage immunity. Am J Respir Cell Mol Biol. 2011;45(2):229–36. doi:10.1165/rcmb.2010-0272OC.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This study was supported by grants from National Natural Science Foundation of China for Priority Areas (NSFC 30972539).

Conflict of interest

The authors declare that there is no potential conflict of interest.

Ethics Statement

All the subjects included in the study have been approved by the Ethics Committee of Harbin Medical University.

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Authors and Affiliations

  1. Department of Epidemiology, Public Health College, Harbin Medical University, 157 Baojian Street, Nangang District, Harbin, Heilongjiang, People’s Republic of China

    Lin Zhu, Yibaina Wang, Ge Jie & Yashuang Zhao

  2. The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China

    Qiang Chi & Junde Zhou

  3. Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China

    Binbin Cui

  4. The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, People’s Republic of China

    Daxun Piao

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  1. Lin Zhu
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  4. Qiang Chi
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Correspondence to Yashuang Zhao.

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Zhu, L., Wang, Y., Jie, G. et al. Association between Toll-like receptor 4 and interleukin 17 gene polymorphisms and colorectal cancer susceptibility in Northeast China. Med Oncol 31, 73 (2014). https://doi.org/10.1007/s12032-014-0073-x

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