Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients

  • Wongwarut Boonyanugomol Department of Sciences and Liberal Arts, Mahidol University, Amnat Charoen Campus, Amnat Charoen, Thailand
  • Kamolchanok Rukseree Department of Sciences and Liberal Arts, Mahidol University, Amnat Charoen Campus, Amnat Charoen, Thailand
  • Worrarat Kongkasame Unit of Endoscopy Medicine, Suppasittiprasong Hospital, Ubon Ratchathani, Thailand
  • Prasit Palittapongarnpim Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand
  • Seung-Chul Baik Department of Microbiology, Gyeongsang National Institute of Health Sciences, School of Medicine, Gyeongsang National University, Jinju, Republic of Korea
  • Mereerat Manwong College of Medicine and Public Health, Ubon Ratchathani University, Ubon Ratchathani, Thailand
Keywords: CXC chemokine ligand 8, CXC chemokine receptor 1, CXC chemokine receptor 2, Gene polymorphism, Helicobacter pylori, Thai

Abstract

CXC Chemokine Ligand 8 (CXCL8) plays an important role in gastric inflammation and in the progression of gastric cancer induced by Helicobacter pylori (H. pylori) infection. The association of CXCL8, CXC Chemokine Receptor 1 (CXCR1), and CXC Chemokine Receptor 2 (CXCR2) polymorphisms with H. pylori infection and gastric cancer progression needs to be investigated in a population within an enigma area consisting of multiple ethnicities, such as Thailand. To analyze the relative risk of H. pylori infection and gastric cancer among Thai gastroduodenal patients, gene polymorphisms in CXCL8 (promoter region -251) and in CXCR1 and CXCR2 (receptors for CXCL8) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele specific-PCR (AS-PCR). We also determined the presence of cytotoxin-associated gene A (cagA) in Thai patients with H. pylori infection. Correlation between the CXCL8 (-251) polymorphism and CXCL8 gene expression was evaluated by quantitative reverse transcriptase-PCR (qRT-PCR). We found a significant association between the T/A and A/A genotypes of CXCL8 (-251) with H. pylori infection. However, no significant correlation was found between the CXCR1 (+2607) and CXCR2 (+1208) gene polymorphisms with H. pylori infection among Thai gastroduodenal subjects. Within the H. pylori-infected group of Thai gastroduodenal patients, no significant differences in cagA were observed. In addition, the A/A genotype of CXCL8 (-251) significantly correlated with the risk of gastric cancer and correlated with higher CXCL8 gene expression levels in Thai gastroduodenal patients. These results suggest that CXCL8 (-251) polymorphisms are associated with H. pylori infection, an increased risk of stronger inflammatory responses, and gastric cancer in Thai gastroduodenal patients.

References

1. Ruggiero P. Helicobacter pylori and inflammation. Curr Pharm Des 2010; 16(38):4225-36.
2. Kutanan W SS, Kamlao A, Kampuansai J. Mitochondrial DNA-HVR1 Variation Reveals Genetic Heterogeneity in Thai-Isan Peoples from the Lower Region of Northeastern Thailand. Advances in Anthropology 2014; 4(1):7-12.
3. Suyasunanont U, Nakkuntod M, Mirasena S. Mitochondrial DNA control region analysis of three ethnic populations in lower Northern part of Thailand. Genet Mol Res 2017; 16(3).
4. Fock KM, Ang TL. Epidemiology of Helicobacter pylori infection and gastric cancer in Asia. J Gastroenterol Hepatol 2010; 25(3):479-86.
5. Fazeli Z, Alebouyeh M, Rezaei Tavirani M, Azimirad M, Yadegar A. Helicobacter pylori CagA induced interleukin-8 secretion in gastric epithelial cells. Gastroenterol Hepatol Bed Bench 2016; 9(Suppl1):S42-S6.
6. Chomvarin C, Namwat W, Chaicumpar K, Mairiang P, Sangchan A, Sripa B, et al. Prevalence of Helicobacter pylori vacA, cagA, cagE, iceA and babA2 genotypes in Thai dyspeptic patients. Int J Infect Dis 2008; 12(1):30-6.
7. Fuccio L, Eusebi LH, Bazzoli F. Gastric cancer, Helicobacter pylori infection and other risk factors. World J Gastrointest Oncol 2010; 2(9):342-7.
8. Craig PM, Territo MC, Karnes WE, Walsh JH. Helicobacter pylori secretes a chemotactic factor for monocytes and neutrophils. Gut 1992; 33(8):1020-3.
9. Schadendorf D, Moller A, Algermissen B, Worm M, Sticherling M, Czarnetzki BM. IL-8 produced by human malignant melanoma cells in vitro is an essential autocrine growth factor. J Immunol 1993; 151(5):2667-75.
10. Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, et al. Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 1992; 258(5089):1798-801.
11. Wang JM, Taraboletti G, Matsushima K, Van Damme J, Mantovani A. Induction of haptotactic migration of melanoma cells by neutrophil activating protein/interleukin-8. Biochem Biophys Res Commun 1990; 169(1):165-70.
12. Vignal A, Milan D, SanCristobal M, Eggen A. A review on SNP and other types of molecular markers and their use in animal genetics. Genet Sel Evol 2002; 34(3):275-305.
13. Chien MH, Yeh CB, Li YC, Wei LH, Chang JH, Peng YT, et al. Relationship of interleukin-8 gene polymorphisms with hepatocellular carcinoma susceptibility and pathological development. J Surg Oncol 2011; 104(7):798-803.
14. Fu JW, Wang KW, Qi ST. Role of IL-8 gene polymorphisms in glioma development in a Chinese population. Genet Mol Res 2016; 15(3).
15. Bidwell JL, Wood NA, Morse HR, Olomolaiye OO, Laundy GJ. Human cytokine gene nucleotide sequence alignments, 1998. Eur J Immunogenet 1998; 25(2-3):83-265.
16. Chen Y, Yang Y, Liu S, Zhu S, Jiang H, Ding J. Association between interleukin 8 -251 A/T and +781 C/T polymorphisms and osteosarcoma risk in Chinese population: a case-control study. Tumour Biol 2016; 37(5):6191-6.
17. Rafrafi A, Chahed B, Kaabachi S, Kaabachi W, Maalmi H, Hamzaoui K, et al. Association of IL-8 gene polymorphisms with non small cell lung cancer in Tunisia: A case control study. Hum Immunol 2013; 74(10):1368-74.
18. Ohyauchi M, Imatani A, Yonechi M, Asano N, Miura A, Iijima K, et al. The polymorphism interleukin 8 -251 A/T influences the susceptibility of Helicobacter pylori related gastric diseases in the Japanese population. Gut 2005; 54(3):330-5.
19. Lee J, Horuk R, Rice GC, Bennett GL, Camerato T, Wood WI. Characterization of two high affinity human interleukin-8 receptors. J Biol Chem 1992; 267(23):16283-7.
20. Renzoni E, Lympany P, Sestini P, Pantelidis P, Wells A, Black C, et al. Distribution of novel polymorphisms of the interleukin-8 and CXC receptor 1 and 2 genes in systemic sclerosis and cryptogenic fibrosing alveolitis. Arthritis Rheum 2000; 43(7):1633-40.
21. Barnes PJ. Genetics and pulmonary medicine. 9. Molecular genetics of chronic obstructive pulmonary disease. Thorax 1999; 54(3):245-52.
22. Taguchi A, Ohmiya N, Shirai K, Mabuchi N, Itoh A, Hirooka Y, et al. Interleukin-8 promoter polymorphism increases the risk of atrophic gastritis and gastric cancer in Japan. Cancer Epidemiol Biomarkers Prev 2005; 14(11 Pt 1):2487-93.
23. Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE, Reece CA, et al. Analyses of the cag pathogenicity island of Helicobacter pylori. Mol Microbiol 1998; 28(1):37-53.
24. Takahashi A, de Andres MC, Hashimoto K, Itoi E, Oreffo RO. Epigenetic regulation of interleukin-8, an inflammatory chemokine, in osteoarthritis. Osteoarthritis Cartilage 2015; 23(11):1946-54.
25. Thomasson M, Hedman H, Junttila TT, Elenius K, Ljungberg B, Henriksson R. ErbB4 is downregulated in renal cell carcinoma--a quantitative RT-PCR and immunohistochemical analysis of the epidermal growth factor receptor family. Acta Oncol 2004; 43(5):453-9.
26. Ritu Saha MAI, Abu Naser Ibne Sattar, Sharmeen Ahmed. The Interleukin-8 -251 A Allele is Associated with Increased Risk of Different Gastroduodenal Diseases in H. pylori Infected Bangladeshi Patients. American Journal of Infectious Diseases and Microbiology 2016; 4(5):102-6.
27. Caleman Neto A, Rasmussen LT, de Labio RW, de Queiroz VF, Smith Mde A, Viani GA, et al. Gene polymorphism of interleukin 1 and 8 in chronic gastritis patients infected with Helicobacter pylori. J Venom Anim Toxins Incl Trop Dis 2014; 20:17.
28. Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, et al. Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35. Genomics 1992; 14(3):685-91.
29. Ahuja SK, Murphy PM. The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor. J Biol Chem 1996; 271(34):20545-50.
30. Murphy PM. Neutrophil receptors for interleukin-8 and related CXC chemokines. Semin Hematol 1997; 34(4):311-8.
31. Ha H, Debnath B, Neamati N. Role of the CXCL8-CXCR1/2 Axis in Cancer and Inflammatory Diseases. Theranostics 2017; 7(6):1543-88.
32. Sharma B, Singh S, Varney ML, Singh RK. Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma. Expert Opin Ther Targets 2010; 14(4):435-42.
33. Javor J, Bucova M, Cervenova O, Kralinsky K, Sadova E, Suchankova M, et al. Genetic variations of interleukin-8, CXCR1 and CXCR2 genes and risk of acute pyelonephritis in children. Int J Immunogenet 2012; 39(4):338-45.
34. Schneider N, Krishna U, Romero-Gallo J, Israel DA, Piazuelo MB, Camargo MC, et al. Role of Helicobacter pylori CagA molecular variations in induction of host phenotypes with carcinogenic potential. J Infect Dis 2009; 199(8):1218-21.
35. Chang YW, Oh CH, Kim JW, Lee JW, Park MJ, Shim JJ, et al. Combination of Helicobacter pylori infection and the interleukin 8 -251 T > A polymorphism, but not the mannose-binding lectin 2 codon 54 G > A polymorphism, might be a risk factor of gastric cancer. BMC Cancer 2017; 17(1):388.
36. McCarron SL, Edwards S, Evans PR, Gibbs R, Dearnaley DP, Dowe A, et al. Influence of cytokine gene polymorphisms on the development of prostate cancer. Cancer Res 2002; 62(12):3369-72.
37. van der Kuyl AC, Polstra AM, Weverling GJ, Zorgdrager F, van den Burg R, Cornelissen M. An IL-8 gene promoter polymorphism is associated with the risk of the development of AIDS-related Kaposi's sarcoma: a case-control study. AIDS 2004; 18(8):1206-8.
38. Xie K. Interleukin-8 and human cancer biology. Cytokine Growth Factor Rev 2001; 12(4):375-91.
Published
2019-08-17
How to Cite
1.
Boonyanugomol W, Rukseree K, Kongkasame W, Palittapongarnpim P, Baik S-C, Manwong M. Genetic Polymorphisms of CXCL8 (−251) Are Associated with the Susceptibility of Helicobacter pylori Infection Increased the Risk of Inflammation and Gastric Cancer in Thai Gastroduodenal Patients. Iran J Allergy Asthma Immunol. 18(4):393-401.
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Original Article(s)