1887

Abstract

Gastric cancer is a health disparity in the Alaska Native people. The incidence of infection, a risk factor for non-cardia gastric adenocarcinoma, is also high. Gastric cancer is partially associated with the virulence of the infecting strain.

To genotype the s, m and i and pathogenicity island () genes in from Alaskans and investigate associations with gastropathy.

We enrolled patients with gastritis, peptic ulcer disease (PUD) and intestinal metaplasia (IM) in 1998–2005 and patients with gastric cancer in 2011–2013. Gastric biopsies were collected and cultured and PCR was performed to detect the presence of the right and left ends of the , the , , and genes and to genotype the s, m and i regions.

We recruited 263 people; 22 (8 %) had no/mild gastritis, 121 (46 %) had moderate gastritis, 40 (15%) had severe gastritis, 38 (14 %) had PUD, 30 (11 %) had IM and 12 (5 %) had gastric cancer. isolates from 150 (57%) people had an intact ; those were associated with a more severe gastropathy (≤0.02 for all comparisons). isolates from 77 % of people had either the s1/i1/m1 (40 %; 94/234) or s2/i2/m2 (37 %; 86/234) genotype. s1/i1/m1 was associated with a more severe gastropathy (≤0.03 for all comparisons).

In this population with high rates of gastric cancer, we found that just over half of the contained an intact and 40 % had the s1/i1/m1 genotype. Infection with these strains was associated with a more severe gastropathy.

Funding
This study was supported by the:
  • Not Applicable , Alaska Science and Technology Foundation , (Award n/a)
  • Not Applicable , Indian Health Service , (Award U269400005)
  • Not Applicable , Indian Health Service , (Award U26IHS300410)
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2020-02-03
2020-02-28
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References

  1. Zamani M, Ebrahimtabar F, Zamani V, Miller WH, Alizadeh-Navaei R et al. Systematic review with meta-analysis: the worldwide prevalence of Helicobacter pylori infection. Aliment Pharmacol Ther 2018; 47:868–876 [CrossRef]
    [Google Scholar]
  2. Tytgat GN RE. Campylobacter pylori and its role in peptic ulcer disease. Gastroenterology Clin N Am 1990; 19:183–196
    [Google Scholar]
  3. Rauws EAJ, Tytgat GNJ. Cure of duodenal ulcer associated with eradication of Helicobacter pylori . The Lancet 1990; 335:1233–1235 [CrossRef]
    [Google Scholar]
  4. The MBJ. Albert Lasker medical research award. Helicobacter pylori. The etiologic agent for peptic ulcer. JAMA 1995; 1995:1064–1066
    [Google Scholar]
  5. Huang JQ, Sridhar S, Chen Y, Hunt RH. Meta-Analysis of the relationship between Helicobacter pylori seropositivity and gastric cancer. Gastroenterology 1998; 114:1169–1179 [CrossRef]
    [Google Scholar]
  6. Bayerdörffer E, Rudolph B, Neubauer A, Thiede C, Lehn N et al. Regression of primary gastric lymphoma of mucosa-associated lymphoid tissue type after cure of Helicobacter pylori infection. The Lancet 1995; 345:1591–1594 [CrossRef]
    [Google Scholar]
  7. Nomura A, Stemmermann GN, Chyou PH, Kato I, Perez-Perez GI et al. Helicobacter pylori infection and gastric carcinoma among Japanese Americans in Hawaii. N Engl J Med 1991; 325:1132–1136 [CrossRef]
    [Google Scholar]
  8. IARC Working group on the evaluation of carcinogenic risks to humans Biological Agents. A review ofhuman carcinogens 2012 pp 1–441
    [Google Scholar]
  9. Kuipers EJ. Review article: exploring the link between Helicobacter pylori and gastric cancer. Aliment Pharmacol Ther 1999; 13:3–11 [CrossRef]
    [Google Scholar]
  10. Kuipers EJ, Thijs JC, Festen HP. The prevalence of Helicobacter pylori in peptic ulcer disease. Aliment Pharmacol Ther 1995; 9:59–69
    [Google Scholar]
  11. Akopyants NS, Clifton SW, Kersulyte D, Crabtree JE, Youree BE et al. Analyses of the CAG pathogenicity island of Helicobacter pylori . Mol Microbiol 1998; 28:37–53 [CrossRef]
    [Google Scholar]
  12. Censini S, Lange C, Xiang Z, Crabtree JE, Ghiara P et al. Cag, a pathogenicity island of Helicobacter pylori, encodes type I-specific and disease-associated virulence factors. Proc Natl Acad Sci U S A 1996; 93:14648–14653 [CrossRef]
    [Google Scholar]
  13. Sozzi M, Tomasini ML, Vindigni C, Zanussi S, Tedeschi R et al. Heterogeneity of CAG genotypes and clinical outcome of Helicobacter pylori infection. J Lab Clin Med 2005; 146:262–270 [CrossRef]
    [Google Scholar]
  14. Jenks PJ, Mégraud F, Labigne A. Clinical outcome after infection with Helicobacter pylori does not appear to be reliably predicted by the presence of any of the genes of the CAG pathogenicity island. Gut 1998; 43:752–758 [CrossRef]
    [Google Scholar]
  15. Maeda S, Yoshida H, Ikenoue T, Ogura K, Kanai F et al. Structure of CAG pathogenicity island in Japanese Helicobacter pylori isolates. Gut 1999; 44:336–341 [CrossRef]
    [Google Scholar]
  16. Nilsson C, Sillén A, Eriksson L, Strand M-L, Enroth H et al. Correlation between CAG pathogenicity island composition and Helicobacter pylori-associated gastroduodenal disease. Infect Immun 2003; 71:6573–6581 [CrossRef]
    [Google Scholar]
  17. Fischer W, Püls J, Buhrdorf R, Gebert B, Odenbreit S et al. Systematic mutagenesis of the Helicobacter pylori CAG pathogenicity island: essential genes for CagA translocation in host cells and induction of interleukin-8. Mol Microbiol 2001; 42:1337–1348 [CrossRef]
    [Google Scholar]
  18. Waskito LA, Miftahussurur M, Lusida MI, Syam AF, Suzuki R et al. Distribution and clinical associations of integrating conjugative elements and CAG pathogenicity islands of Helicobacter pylori in Indonesia. Sci Rep 2018; 8:6073 [CrossRef]
    [Google Scholar]
  19. Rohde M, Püls J, Buhrdorf R, Fischer W, Haas R et al. A novel sheathed surface organelle of the Helicobacter pylori CAG type IV secretion system. Mol Microbiol 2003; 49:219–234 [CrossRef]
    [Google Scholar]
  20. Blaser MJ, Perez-Perez GI, Kleanthous H et al. Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach. Cancer Res 1995; 55:2111–2115
    [Google Scholar]
  21. Parsonnet J, Friedman GD, Orentreich N, Vogelman H et al. Risk for gastric cancer in people with cagA positive or CagA negative Helicobacter pylori infection. Gut 1997; 40:297–301 [CrossRef]
    [Google Scholar]
  22. pormohammad A, Ghotaslou R, Leylabadlo HE, Nasiri MJ, Dabiri H et al. Risk of gastric cancer in association with Helicobacter pylori different virulence factors: a systematic review and meta-analysis. Microb Pathog 2018; 118:214–219 [CrossRef]
    [Google Scholar]
  23. Higashi H et al. Shp-2 tyrosine phosphatase as an intracellular target of Helicobacter pylori CagA protein. Science 2002; 295:683–686 [CrossRef]
    [Google Scholar]
  24. Argent RH, Kidd M, Owen RJ, Thomas RJ, Limb MC et al. Determinants and consequences of different levels of CagA phosphorylation for clinical isolates of Helicobacter pylori . Gastroenterology 2004; 127:514–523 [CrossRef]
    [Google Scholar]
  25. Hayashi T, Senda M, Suzuki N, Nishikawa H, Ben C et al. Differential mechanisms for SHP2 binding and activation are exploited by geographically distinct Helicobacter pylori CagA oncoproteins. Cell Rep 2017; 20:2876–2890 [CrossRef]
    [Google Scholar]
  26. Montecucco C, de Bernard M. Molecular and cellular mechanisms of action of the vacuolating cytotoxin (VacA) and neutrophil-activating protein (HP-NAP) virulence factors of Helicobacter pylori . Microbes and Infection 2003; 5:715–721 [CrossRef]
    [Google Scholar]
  27. Graham DY. Pathogenesis of increased sucrose permeability in H. pylori gastritis. Dig Dis Sci 2000; 45:889 [CrossRef]
    [Google Scholar]
  28. Papini E, Satin B, Norais N, de Bernard M, Telford JL et al. Selective increase of the permeability of polarized epithelial cell monolayers by Helicobacter pylori vacuolating toxin. J Clin Invest 1998; 102:813–820 [CrossRef]
    [Google Scholar]
  29. Atherton JC, Cao P, Peek RM, Tummuru MK, Blaser MJ et al. Mosaicism in vacuolating cytotoxin alleles of Helicobacter pylori. Association of specific vacA types with cytotoxin production and peptic ulceration. J Biol Chem 1995; 270:17771–17777 [CrossRef]
    [Google Scholar]
  30. Ferreira RM, Machado JC, Letley D, Atherton JC, Pardo ML et al. A novel method for genotyping the Helicobacter pylori vacA intermediate region directly in gastric biopsy specimens. J Clin Microbiol 2012; 50:3983–3989 [CrossRef]
    [Google Scholar]
  31. Atherton JC, Peek RM, Tham KT, Cover TL, Blaser MJ et al. Clinical and pathological importance of heterogeneity in vacA, the vacuolating cytotoxin gene of Helicobacter pylori . Gastroenterology 1997; 112:92–99 [CrossRef]
    [Google Scholar]
  32. Gunn MC, Stephens JC, Stewart JA, Rathbone BJ, West KP et al. The significance of cagA and vacA subtypes of Helicobacter pylori in the pathogenesis of inflammation and peptic ulceration. J Clin Pathol 1998; 51:761–764 [CrossRef]
    [Google Scholar]
  33. Wang HJ, Kuo CH, Yeh AA, Chang PC, Wang WC et al. Vacuolating toxin production in clinical isolates of Helicobacter pylori with different vacA genotypes. J Infect Dis 1998; 178:207–212 [CrossRef]
    [Google Scholar]
  34. Basso D, Navaglia F, Brigato L, Piva MG, Toma A et al. Analysis of Helicobacter pylori vacA and cagA genotypes and serum antibody profile in benign and malignant gastroduodenal diseases. Gut 1998; 43:182–186 [CrossRef]
    [Google Scholar]
  35. Navaglia F, Basso D, Piva MG, Brigato L, Stefani A et al. Helicobacter pylori cytotoxic genotype is associated with peptic ulcer and influences serology. Am J Gastroenterol 1998; 93:227–230 [CrossRef]
    [Google Scholar]
  36. Garza-González E, Bosques-Padilla FJ, Pérez-Pérez GI, Flores-Gutiérrez JP, Tijerina-Menchaca R et al. Association of gastric cancer, HLA-DQA1, and infection with Helicobacter pylori cagA+ and VacA+ in a Mexican population. J Gastroenterol 2004; 39:1138–1142 [CrossRef]
    [Google Scholar]
  37. Sugimoto M, Yamaoka Y. The association of vacA genotype and Helicobacter pylori-related disease in Latin American and African populations. Clin Microbiol Infect 2009; 15:835–842 [CrossRef]
    [Google Scholar]
  38. Carmack AM, Schade TL, Sallison I et al. Cancer in Alaska native people: 1969-2013 the 45-Year report; 2015
  39. Parkinson AJ, Gold BD, Bulkow L, Wainwright RB, Swaminathan B et al. High prevalence of Helicobacter pylori in the Alaska native population and association with low serum ferritin levels in young adults. Clin Diagn Lab Immunol 2000; 7:885–888 [CrossRef]
    [Google Scholar]
  40. Miernyk KM, Bulkow LR, Gold BD, Bruce MG, Hurlburt DH et al. Prevalence of Helicobacter pylori among Alaskans: Factors associated with infection and comparison of urea breath test and anti- Helicobacter pylori IgG antibodies. Helicobacter 2018; 23:e12482 [CrossRef]
    [Google Scholar]
  41. Mosites E, Bruden D, Morris J, Reasonover A, Rudolph K et al. Antimicrobial resistance among Helicobacter pylori isolates in Alaska, 2000-2016. J Glob Antimicrob Resist 2018; 15:148–153 [CrossRef]
    [Google Scholar]
  42. Bruce MG, Bruden D, McMahon BJ et al. The relationship between antimicrobial resistance and treatment outcome for Helicobacter pylori infections in native and non-native persons residing in Alaska. Helicobacter 2007; 12:450–451
    [Google Scholar]
  43. McMahon BJ, Bruce MG, Hennessy TW, Bruden DL, Sacco F et al. Reinfection after successful eradication of Helicobacter pylori: a 2-year prospective study in Alaska natives. Aliment Pharmacol Ther 2006; 23:1215–1223 [CrossRef]
    [Google Scholar]
  44. Bruce MG, Bruden DL, Morris JM, Reasonover AL, Sacco F et al. Reinfection after successful eradication of Helicobacter pylori in three different populations in Alaska. Epidemiol Infect 2015; 143:1236–1246 [CrossRef]
    [Google Scholar]
  45. McMahon BJ, Bruce MG, Koch A, Goodman KJ, Tsukanov V et al. The diagnosis and treatment of Helicobacter pylori infection in Arctic regions with a high prevalence of infection: Expert Commentary. Epidemiol Infect 2016; 144:225–233 [CrossRef]
    [Google Scholar]
  46. Bruce MG, Miernyk K, Sacco F, Thomas T, McMahon B et al. Response to editorial. Helicobacter 2019; 24:e12558 [CrossRef]
    [Google Scholar]
  47. Miernyk K, Morris J, Bruden D, McMahon B, Hurlburt D et al. Characterization of Helicobacter pylori cagA and vacA Genotypes among Alaskans and Their Correlation with Clinical Disease. J Clin Microbiol 2011; 49:3114–3121 [CrossRef]
    [Google Scholar]
  48. Nolen LD, Bruden D, Miernyk K, McMahon BJ, Sacco F et al. H. pylori -associated pathologic findings among Alaska native patients. Int J Circumpolar Health 2018; 77:1510715 [CrossRef]
    [Google Scholar]
  49. McMahon BJ, Hennessy TW, Bensler JM, Bruden DL, Parkinson AJ et al. The Relationship among Previous Antimicrobial Use, Antimicrobial Resistance, and Treatment Outcomes for Helicobacter pylori Infections. Ann Intern Med 2003; 139:463–469 [CrossRef]
    [Google Scholar]
  50. Lehmann EL, D'Abrera HJM. Nonparametrics: Statistical Methods Based on Ranks New York: Springer Science & Business Media; 2006
    [Google Scholar]
  51. Linz B, Balloux F, Moodley Y, Manica A, Liu H et al. An African origin for the intimate association between humans and Helicobacter pylori . Nature 2007; 445:915918 [CrossRef]
    [Google Scholar]
  52. Olbermann P, Josenhans C, Moodley Y, Uhr M, Stamer C et al. A global overview of the genetic and functional diversity in the Helicobacter pylori CAG pathogenicity island. PLoS Genet 2010; 6:e1001069 [CrossRef]
    [Google Scholar]
  53. Khatoon J, Prasad KN, Prakash Rai R, Ghoshal UC, Krishnani N et al. Association of heterogenicity of Helicobacter pylori cag pathogenicity island with peptic ulcer diseases and gastric cancer. Br J Biomed Sci 2017; 74:121–126 [CrossRef]
    [Google Scholar]
  54. Ikenoue T, Maeda S, Ogura K, Akanuma M, Mitsuno Y et al. Determination of Helicobacter pylori virulence by simple gene analysis of the CAG pathogenicity island. Clinical and Vaccine Immunology 2001; 8:181–186 [CrossRef]
    [Google Scholar]
  55. Hanada K, Uchida T, Tsukamoto Y, Watada M, Yamaguchi N et al. Helicobacter pylori infection introduces DNA double-strand breaks in host cells. Infect Immun 2014; 82:4182–4189 [CrossRef]
    [Google Scholar]
  56. Ali M, Khan AA, Tiwari SK, Ahmed N, Rao LV et al. Association between cag-pathogenicity island in Helicobacter pylori isolates from peptic ulcer, gastric carcinoma, and non-ulcer dyspepsia subjects with histological changes. World J Gastroenterol 2005; 11:6815–6822 [CrossRef]
    [Google Scholar]
  57. Johnson EM, Gaddy JA, Voss BJ, Hennig EE, Cover TL et al. Genes required for assembly of pili associated with the Helicobacter pylori CAG type IV secretion system. Infect Immun 2014; 82:3457–3470 [CrossRef]
    [Google Scholar]
  58. Frick-Cheng AE, Pyburn TM, Voss BJ, McDonald WH, Ohi MD et al. Molecular and Structural Analysis of the Helicobacter pylori cag Type IV Secretion System Core Complex. mBio 2016; 7:e02001–02015 [CrossRef]
    [Google Scholar]
  59. Kauser F, Hussain MA, Ahmed I, Srinivas S, Devi SM et al. Comparative genomics of Helicobacter pylori isolates recovered from ulcer disease patients in England. BMC Microbiol 2005; 5:32 [CrossRef]
    [Google Scholar]
  60. Higashi H, Tsutsumi R, Fujita A, Yamazaki S, Asaka M et al. Biological activity of the Helicobacter pylori virulence factor CagA is determined by variation in the tyrosine phosphorylation sites. Proc Natl Acad Sci U S A 2002; 99:14428–14433 [CrossRef]
    [Google Scholar]
  61. Reyes-Leon A, Atherton JC, Argent RH, Puente JL, Torres J et al. Heterogeneity in the activity of Mexican Helicobacter pylori strains in gastric epithelial cells and its association with diversity in the cagA gene. Infect Immun 2007; 75:3445–3454 [CrossRef]
    [Google Scholar]
  62. Zhang X-S, Tegtmeyer N, Traube L, Jindal S, Perez-Perez G et al. A specific A/T polymorphism in Western tyrosine phosphorylation B-motifs regulates Helicobacter pylori CagA epithelial cell interactions. PLoS Pathog 2015; 11:e1004621 [CrossRef]
    [Google Scholar]
  63. Rhead JL, Letley DP, Mohammadi M, Hussein N, Mohagheghi MA et al. A new Helicobacter pylori vacuolating cytotoxin determinant, the intermediate region, is associated with gastric cancer. Gastroenterology 2007; 133:926–936 [CrossRef]
    [Google Scholar]
  64. Basso D, Zambon C-F, Letley DP, Stranges A, Marchet A et al. Clinical relevance of Helicobacter pylori cagA and vacA gene polymorphisms. Gastroenterology 2008; 135:91–99 [CrossRef]
    [Google Scholar]
  65. Douraghi M, Talebkhan Y, Zeraati H, Ebrahimzadeh F, Nahvijoo A et al. Multiple gene status in Helicobacter pylori strains and risk of gastric cancer development. Digestion 2009; 80:200–207 [CrossRef]
    [Google Scholar]
  66. Ogiwara H, Sugimoto M, Ohno T, Vilaichone R-K, Mahachai V et al. Role of deletion located between the intermediate and middle regions of the Helicobacter pylori vacA gene in cases of gastroduodenal diseases. J Clin Microbiol 2009; 47:3493–3500 [CrossRef]
    [Google Scholar]
  67. Yordanov D, Boyanova L, Markovska R, Gergova G, Mitov I et al. Significance of Helicobacter pylori vacA intermediate region genotyping—a Bulgarian study. Diagn Microbiol Infect Dis 2012; 74:253–257 [CrossRef]
    [Google Scholar]
  68. Mottaghi B, Safaralizadeh R, Bonyadi M, Latifi-Navid S, Somi MH et al. Helicobacter pylori vacA I region polymorphism but not babA2 status associated to gastric cancer risk in northwestern Iran. Clin Exp Med 2016; 16:57–63 [CrossRef]
    [Google Scholar]
  69. Yamaoka Y, Osato MS, Sepulveda AR, Gutierrez O, Figura N et al. Molecular epidemiology of Helicobacter pylori: separation of H. pylori from East Asian and non-Asian countries. Epidemiol Infect 2000; 124:91–96 [CrossRef]
    [Google Scholar]
  70. Panayotopoulou EG, Sgouras DN, Papadakos K, Kalliaropoulos A, Papatheodoridis G et al. Strategy to characterize the number and type of repeating EPIYA phosphorylation motifs in the carboxyl terminus of CagA protein in Helicobacter pylori clinical isolates. J Clin Microbiol 2007; 45:488–495 [CrossRef]
    [Google Scholar]
  71. Antonio-Rincón F, López-Vidal Y, Castillo-Rojas G, Lazcano-Ponce EC, Ponce-de-León S et al. Pathogenicity island CAG, vacA and IS605 genotypes in Mexican strains of Helicobacter pylori associated with peptic ulcers. Ann Clin Microbiol Antimicrob 2011; 10:18 [CrossRef]
    [Google Scholar]
  72. Hsu P-I, Hwang I-ran, Cittelly D, Lai K-H, El-Zimaity HMT et al. Clinical presentation in relation to diversity within the Helicobacter pylori CAG pathogenicity island. Am J Gastroenterol 2002; 97:2231–2238 [CrossRef]
    [Google Scholar]
  73. Audibert C, Burucoa C, Janvier B, Fauchere JL et al. Implication of the structure of the Helicobacter pylori CAG pathogenicity island in induction of interleukin-8 secretion. Infect Immun 2001; 69:1625–1629 [CrossRef]
    [Google Scholar]
  74. Yamaoka Y, Kodama T, Gutierrez O et al. Relationship between Helicobacter pylori iceA, cagA, and vacA status and clinical outcome: studies in four different countries. J Clin Microbiol 1999; 37:2274–2279
    [Google Scholar]
  75. Mukhopadhyay AK, Kersulyte D, Jeong J-Y, Datta S, Ito Y et al. Distinctiveness of genotypes of Helicobacter pylori in Calcutta, India. J Bacteriol 2000; 182:3219–3227 [CrossRef]
    [Google Scholar]
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