期刊论文详细信息
BMC Gastroenterology
Higher frequency of cagA EPIYA-C Phosphorylation Sites in H. pylori strains from first-degree relatives of gastric cancer patients
Lucia LBC Braga2  Aldo AM Lima3  Richard L Guerrant1  Sérgio A Batista4  Andreia MC Rocha4  Gifone A Rocha4  André MN Fialho4  Andréa BC Fialho2  Manuel B Braga-Neto2  Maria HRB Goncalves2  Cícero ISM Silva2  Dulciene MM Queiroz4 
[1] Center for Global Health, University of Virginia, Charlottesville, VA, USA;Clinical Research Unity – Department of Internal Medicine, University Hospital Walter Cantídio – Federal University of Ceará, P.O. Box: 60430270, Fortaleza, Ceará, Brazil;Department of Physiology and Pharmacology, Federal University of Ceará, Fortaleza, Ceará, Brazil;Laboratory of Research in Bacteriology, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil
关键词: H. pylori/vacA;    H. pylori CagA-EPIYA;    Gastric cancer;    Helicobacter pylori;   
Others  :  1121892
DOI  :  10.1186/1471-230X-12-107
 received in 2012-02-29, accepted in 2012-08-08,  发布年份 2012
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【 摘 要 】

Background

To evaluate the prevalence of more virulent H. pylori genotypes in relatives of gastric cancer patients and in patients without family histories of gastric cancer.

Methods

We evaluated prospectively the prevalence of the infection by more virulent H. pylori strains in 60 relatives of gastric cancer patients comparing the results with those obtained from 49 patients without family histories of gastric cancer. H. pylori status was determined by the urease test, histology and presence of H. pylori ureA. The cytotoxin associated gene (cagA), the cagA-EPIYA and vacuolating cytotoxin gene (vacA) were typed by PCR and the cagA EPIYA typing was confirmed by sequencing.

Results

The gastric cancer relatives were significant and independently more frequently colonized by H. pylori strains with higher numbers of CagA-EPIYA-C segments (OR = 4.23, 95%CI = 1.53–11.69) and with the most virulent s1m1 vacA genotype (OR = 2.80, 95%CI = 1.04–7.51). Higher numbers of EPIYA-C segments were associated with increased gastric corpus inflammation, foveolar hyperplasia and atrophy. Infection by s1m1 vacA genotype was associated with increased antral and corpus gastritis.

Conclusions

We demonstrated that relatives of gastric cancer patients are more frequently colonized by the most virulent H. pylori cagA and vacA genotypes, which may contribute to increase the risk of gastric cancer.

【 授权许可】

   
2012 Queiroz et al.; licensee BioMed Central Ltd.

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【 参考文献 】
  • [1]Parsonnet J, Friedman GD, Vandersteen DO: Helicobacter pylori and the risk of gastric carcinoma. N Engl J Med 1991, 25:1127-1131.
  • [2]Brenner H, Arndt V, Stürmer T, Stegmaier C, Ziegler H, Dhom G: Individual and joint contribution of family history and Helicobacter pylori infection to the risk of gastric carcinoma. Cancer 2000, 88:274-279.
  • [3]Uemura N, Okamoto S: Effect of Helicobacter pylori eradication on subsequent development of cancer after endoscopic resection of early gastric cancer in Japan. Gastroenterol Clin North Am 2000, 29:819-827.
  • [4]Chang YW, Han YS, Lee DK, Kim HJ, Lim HS, Moon JS, et al.: Role of Helicobacter pylori infection among offspring or siblings of gastric cancer patients. Int J Cancer 2002, 101:469-474.
  • [5]Jablonska M, Chlumska A: Genetic factors in the development of gastric precancerous lesions – a role of Helicobacter pylori? Int J Cancer 2001, 95:477-481.
  • [6]Segal ED, Cha J, Lo J, Falkow S, Tompkins LS: Altered states: Involvement of phosphorylated CagA in the induction of host cellular growth changes by Helicobacter pylori. Proc Natl Acad Sci USA 1999, 96:14559-14564.
  • [7]Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R: Translocation of Helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 2000, 287:1497-1500.
  • [8]Higashi H, Tsutsumi R, Muto S, Sugiyama T, Azuma T, Asaka M, et al.: SHP-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 2002, 295:683-686.
  • [9]Naito M, Yamazaki T, Tsutsumi R, Higashi H, Onoe K, Yamazaki S, et al.: Influence of EPIYA-repeat polymorphism on the phosphorylation-dependent biological activity of Helicobacter pylori CagA. Gastroenterology 2006, 130:1181-1190.
  • [10]Hatakeyama M: Oncogenic mechanisms of the Helicobacter pylori CagA protein. Nat Rev Cancer 2004, 4:688-694.
  • [11]Argent RH, Hale JL, El-Omar EM, Atherton JC: Differences in Helicobacter pylori CagA tyrosine phosphorylation motif patterns between western and East Asian strains, and influences on interleukin-8 secretion. J of Med Microb 2008, 57:1062-1067.
  • [12]Yamaoka Y, El-Zimaity HMT, Gutierrez O, Figura N, Kim JK, Kodama T, et al.: Relationship between the cagA 3 ' repeat region of Helicobacter pylori, gastric histology, and susceptibility to low pH. Gastroenterology 1999, 117:342-349.
  • [13]Basso D, Zambon CF, Letley DP, Stranges A, Marchet A, Rhead JL, et al.: Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 2008, 135:91-99.
  • [14]Sicinschi LA, Correa P, Peek RM, Camargo MC, Piazuelo MB, Romero-Gallo J, et al.: CagA C-terminal variations in Helicobacter pylori strains from Colombian patients with gastric precancerous lesions. Clin Microbiol Infect 2010, 16:369-378.
  • [15]Batista SA, Rocha GA, Rocha AM, Saraiva IE, Cabral MM, Oliveira RC, et al.: Higher number of Helicobacter pylori CagA EPIYA C phosphorylation sites increases the risk of gastric cancer, but not duodenal ulcer. BMC Microbiol 2011, 11:61. BioMed Central Full Text
  • [16]Atherton JC, Cao P, Peek RM, Tummuru MK, Blaser MJ, Cover TL: Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995, 270:17771-177777.
  • [17]Willihite DC, Blanke SR: Helicobacter pylori vauolating cytotoxin induces activation of the proapoptotic enters cells, localizes to the mithochondria, and induces mithochondrial membrane permeability changes correlated to toxin channel activity. Cell Microbiol 2004, 6:143-154.
  • [18]Yamasaki E, Wada A, Kumatori A, Nakagawa I, Funao J, Nakayama M, et al.: Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation. J Biol Chem 2006, 281:11250-11259.
  • [19]Ashour AA, Magalhães PP, Mendes EN, Collares GB, de Gusmão VR, Queiroz DM, et al.: Distribution of vacA genotypes in Helicobacter pylori strains isolated from Brazilian adult patients with gastritis, duodenal ulcer or gastric carcinoma. FEMS Immunol Med Microbiol 2002, 33:173-178.
  • [20]Motta CR, Cunha MP, Queiroz DM, Cruz FW, Guerra EJ, Mota RM, et al.: Gastric precancerous lesions and Helicobacter pylori infection in relatives of gastric cancer patients from northeastern Brazil. Digestion 2008, 78:3-8.
  • [21]Argent RH, Thomas RJ, Aviles-Jimenez F, Letley DP, Limb MC, El-Omar EM, Atheton JC: Toxigenic Helicobacter pylori infection precedes hypochlorydria in cancer relatives, and H. pylori evolves in these families. Clin Canc Res 2008, 14:2227-2235.
  • [22]Dixon MF, Genta RM, Yardley JH, Correa P: Classification and grading of gastritis. The updated Sydney System. International Workshop on the Histopathology of Gastritis, Houston 1994. Am J Surg Pathol 1996, 20:1161-1181.
  • [23]Monteiro MA, Chan KH, Rasko DA, Taylor DE, Zheng PY, Appelmelk BJ, et al.: Simultaneous expression of type 1 and type 2 Lewis blood group antigens by Helicobacter pylori lipopolysaccharides. Molecular mimicry between h. pylori lipopolysaccharides and human gastric epithelial cell surface glycoforms. J Biol Chem 1998, 273:11533-11543.
  • [24]Clayton CL, Kleanthous H, Coates PJ, Morgan DD, Tabaqchali S: Sensitive Detection of Helicobacter-pylori by Using Polymerase Chain-Reaction. J Clin Microbiol 1992, 30:192-200.
  • [25]van Doorn LJ, Figueiredo C, Sanna R, Plaisier A, Schneeberger P, de Boer W, et al.: Clinical relevance of the cagA, vacA, and iceA status of Helicobacter pylori. Gastroenterology 1998, 115:58-66.
  • [26]Atherton JC, Cover TL, Wells RJ, Morales MR, Hawley CJ, Blaser MJ: Simple accurate PCR-based system for typing vaucolating cytotoxin alleles of Helicobacter pylori. J Clin Microbiol 1999, 37:2979-2982.
  • [27]Kelly SM, Pitcher MC, Farmery SM, Gibson GR: Isolation of Helicobacter pylori from feces of patients with dyspepsia in the United Kingdom. Gastroenterology 1994, 107:1671-1674.
  • [28]Peek RM, Miller GG, Tham KT, Perez-Perez GI, Cover TL, Atherton JC, et al.: Detection of Helicobacter pylori gene expression in human gastric mucosa. J Clin Microbiol 1995, 33:28-32.
  • [29]Yamaoka Y, Kodama T, Kashima K, Graham DY, Sepulveda AR: Variants of the 3' region of the cagA gene in Helicobacter pylori isolates from patients with different H. pylori-associated diseases. J Clin Microbiol 1998, 36:2258-2263.
  • [30]Argent RH, Kidd M, Owen RJ, Thomas RJ, Limb MC, Atherton JC: Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori. Gastroenterology 2004, 127:514-523.
  • [31]Hosmer DW, Lemeshow S (Eds): Applied Logistic Regression, JH. New York: Wiley Interscience Publication; 2000.
  • [32]Hatakeyama M: Anthorpological and clinical implications for structural diversity of the Helicobacter pylori CagA oncoprotein. Cancer Sci 2011, 102:36-43.
  • [33]Rocha GA, Rocha AM, Silva LD, Santos A, Bocewicz AC, Queiroz R, Rde M, et al.: Transmission of Helicobacter pylori infection in families of preschool-aged children from Minas Gerais, Brazil. Trop Med Int Health 2003, 8:987-991.
  • [34]Kivi M, Johansson AL, Reilly M, Tindberg Y: Helicobacter pylori status in family members as risk factors for infection in children. Epidemiol Infect 2005, 133:645-652.
  • [35]El-Omar EM, Carrington M, Chow WH, McColl KE, Bream JH, Young HA, et al.: Interleukin-1 polymorphisms assocaited with increased risk of gastric cancer. Nature 2000, 404:398-402.
  • [36]El-Omar EM, Rabkin CS, Gammon MD, Vaughan TL, Risch HA, Schoenberg JB, et al.: Increased risk of noncardia gastric cancer associated with porinfalmmatory cytokine genes polymorhisms. Gastroenterology 2003, 124:1193-1201.
  • [37]Machado JC, Figueiredo C, Canedo P, Pharoah P, Carvalho R, Nabais S, et al.: A proinflammatory genetic profile increases the risk for chronic atrophic gastritis and gastric carcinoma. Gastroenterology 2003, 125:364-371.
  • [38]Rocha GA, Guerra JB, Rocha AMC, Saraiva IEB, da Silva DA, de Oliveira CA, et al.: IL1RN polymorphic gene and cagA-positive status independently increase the risk of noncardia gastric carcinoma. Int J Cancer 2005, 115:678-683.
  • [39]Figueiredo C, Machado JC, Pharoah P, Seruca R, Sousa S, Carvalho R, et al.: Helicobacter pylori and interleukin 1 genotyping: an opportunity to identify high-risk individuals for gastric carcinoma. J Natl Cancer Instit 2002, 94:1680-1687.
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