Abstract
Background
Genetic polymorphisms of Toll-like receptors play important roles in gastric carcinogenesis. The aim of this study was to determine the role of TLR2-196 to -174 ins/del polymorphism in gastric cancer susceptibility and prognosis.
Methods
This study included 520 people from southern China. Samples were genotyped by the allele-specific polymerase chain reaction, among which 10% were randomly selected for sequencing. The serological method was used to determine Helicobacter pylori.
Results
The TLR2 genotype was not associated with the risk of H. pylori infection. The del/del genotype exhibited significantly higher gastric cancer risk (adjusted OR 2.59, 95% CI 1.33‒5.07) than that of the ins/ins genotype. Further stratification analyses demonstrated that the del/del genotype was associated with a risk of intestinal gastric cancer (adjusted OR 2.62, 95% CI 1.34–5.14). In addition, the presence of the del/del genotype and the H. pylori infection conferred a synergistic effect (OR 3.04, 95% CI 1.33‒6.98) for the development of gastric cancer. The del/del genotype was not associated with a poor prognosis in gastric cancer patients.
Conclusion
The del/del genotype is associated with an increased gastric cancer risk in the southern Chinese population. However, TLR2 polymorphism is neither associated with H. pylori infection, nor with a poor prognosis.
Similar content being viewed by others
References
Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108
Chen W, Zheng R, Zhang S et al (2017) Cancer incidence and mortality in China, 2013. Cancer Lett 401:63–71
Gobert AP, Wilson KT (2017) Human and Helicobacter pylori interactions determine the outcome of gastric diseases. Curr Top Microbiol Immunol 400:27–52
Lochhead P, El-Omar EM (2007) Helicobacter pylori infection and gastric cancer. Best Pract Res Clin Gastroenterol 21(2):281–297
Hold GL, Rabkin CS, Chow WH et al (2007) A functional polymorphism of toll-like receptor 4 gene increases risk of gastric carcinoma and its precursors. Gastroenterology 132(3):905–912
Barton GM (2008) A calculated response: control of inflammation by the innate immune system. J Clin Invest 118(2):413–420
Akira S, Hemmi H (2003) Recognition of pathogen-associated molecular patterns by TLR family. Immunol Lett 85(2):85–95
Akira S, Takeda K (2004) Toll-like receptor signalling. Nat Rev Immunol 4(7):499–511
Pimentel-Nunes P, Afonso L, Lopes P et al (2011) Increased expression of toll-like receptors (TLR) 2, 4 and 5 in gastric dysplasia. Pathol Oncol Res 17(3):677–683
Nemati M, Larussa T, Khorramdelazad H et al (2017) Toll-like receptor 2: An important immunomodulatory molecule during Helicobacter pylori infection. Life Sci 178:17–29
Smith MF Jr, Mitchell A, Li G et al (2003) Toll-like receptor (TLR) 2 and TLR5, but not TLR4, are required for Helicobacter pylori-induced NF-kappa B activation and chemokine expression by epithelial cells. J Biol Chem 278(35):32552–32560
Haehnel V, Schwarzfischer L, Fenton MJ et al (2002) Transcriptional regulation of the human toll-like receptor 2 gene in monocytes and macrophages. J Immunol 168(11):5629–5637
Chen YC, Hsiao CC, Chen CJ et al (2010) Toll-like receptor 2 gene polymorphisms, pulmonary tuberculosis, and natural killer cell counts. BMC Med Genet 30:11:17
Takeda K, Kaisho T, Akira S (2003) Toll-like receptors. Annu Rev Immunol 21:335–376
Noguchi E, Nishimura F, Fukai H 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(2):177–183
Theodoropoulos GE, Saridakis V, Karantanos T et al (2012) Toll-like receptors gene polymorphisms may confer increased susceptibility to breast cancer development. Breast 21(4):534–538
Nischalke HD, Coenen M, Berger C et al (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(6):1470–1475
Srivastava K, Srivastava A, Kumar A et al (2010) Significant association between toll-like receptor gene polymorphisms and gallbladder cancer. Liver Int 30(7):1067–1072
Tahara T, Arisawa T, Wang F et al (2007) Toll-like receptor 2-196 to -174del polymorphism influences the susceptibility of Japanese people to gastric cancer. Cancer Sci 98(11):1790–1794
Zeng HM, Pan KF, Zhang Y et al (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 Biomarkers Prev 20(12):2594–2602
Wang X, Yang Y, Shi R et al (2008) An evaluation of a serologic test with a current infection marker of Helicobacter pylori before and after eradication therapy in Chinese. Helicobacter 13:49–55
Hishida A, Matsuo K, Goto Y 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(4):251–257
Chen B, Luo MX, Zhou X et al (2016) Correlation between interleukin-1β-511 C/T polymorphism and gastric cancer in Chinese populations: a meta-analysis. Med Sci Monit 24(22):1742–1750
van der Stoep N, Quinten E, van den Elsen PJ (2002) Transcriptional regulation of the MHC class II trans-activator (CIITA) promoter III: identification of a novel regulatory region in the 5′-untranslated region and an important role for cAMP-responsive element binding protein 1 and activating transcription factor-1 in CIITA-promoter III transcriptional activation in B lymphocytes. J Immunol 169(9):5061–5071
van der Velden AW, Thomas AA (1999) The role of the 5′ untranslated region of an mRNA in translation regulation during development. Int J Biochem Cell Biol 31(1):87–106
Li S, Cao M, Song L et al (2016) The contribution of toll-like receptor 2 on Helicobacter pylori activation of the nuclear factor-kappa B signaling pathway in gastric epithelial cells. Microb Pathog 98:63–68
Parsonnet J, Friedman GD, Vandersteen DP et al (1991) Helicobacter pylori infection and the risk of gastric carcinoma. N Engl J Med 325(16):1127–1131
Wang F, Meng W, Wang B et al (2014) Helicobacter pylori-induced gastric inflammation and gastric cancer. Cancer Lett 345(2):196–202
Marqués-Lespier JM, González-Pons M, Cruz-Correa M (2016) Current perspectives on gastric cancer. Gastroenterol Clin North Am 45(3):413–428
Acknowledgements
This study was supported by the Applied Basic Research Fund of Changzhou, China (CJ20140022, CJ20179034), Young medical talents of Jiangsu province (QNRC2016269), the High-level Medicine Talents Training Project (2016CZBJ022), and the Youth Science and Technology Project of Changzhou Health and Family Planning Commission (QN201601).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Huang, J., Hang, JJ., Qin, XR. et al. Interaction of H. pylori with toll-like receptor 2-196 to -174 ins/del polymorphism is associated with gastric cancer susceptibility in southern China. Int J Clin Oncol 24, 494–500 (2019). https://doi.org/10.1007/s10147-018-1379-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10147-018-1379-z