Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric Cancer

Jones, Kathleen R.; Joo, Young Min; Jang, Sungil; Yoo, Yun‐Jung; Lee, Hak Sung; Chung, In Sik; Olsen, Cara; Whitmire, Jeannette M.; Merrell, D. Scott; Heon, Jeong

doi:10.1128/jcm.02330-08

Cited by 120 publications

(144 citation statements)

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“…Within this population, 49.6% (126 patients) were female, with an age range of 21 to 86 years and a mean age of 52 years, and 50.4% (128 patients) were male, with a mean age of 50 years and an age range of 14 to 82 years. Of these samples, 11.8% were from patients with cancer, 42.9% were from patients with peptic ulcer disease (21.7% gastric ulcers and 21.3% duodenal ulcers), and 45.3% were from patients with gastritis (24).…”

Section: Resultsmentioning

confidence: 99%

“…The strains used for this study were previously used for the characterization of the distribution of cagA alleles (24) and represent 260 strains obtained from patients presenting with gastric maladies; 254 of those strains have complete epidemiological data (see Table S1 in the supplemental material). The mean patient age was 51 years, with an age range of 14 to 86 years (Table 2).…”

Section: Resultsmentioning

confidence: 99%

“…The South Korean H. pylori clinical isolates used in this study were previously described by Jones et al (24) and included 115 gastritis isolates, 55 gastric ulcer isolates, 54 duodenal ulcer isolates, and 30 gastric cancer isolates with epidemiological data on age and gender. H. pylori stocks preserved at Ϫ80°C were grown and expanded on antibiotic-supplemented horse blood agar plates under microaerophilic conditions created by an Anoxomat evacuation/replacement system (Spiral Biotech, Norwood, MA) as previously described (9,24).…”

Section: Methodsmentioning

confidence: 99%

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Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA

et al. 2010

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Gastritis, peptic ulcer disease, and gastric cancer are a few of the diverse disease manifestations that have been shown to be associated with infection by Helicobacter pylori. Why some individuals develop more severe forms of disease remains largely unknown. In this study, 225 South Korean strains were genotyped for vacA and then analyzed to determine if particular genotypes varied across disease state, sex, or cagA allele. Of these strains, 206 strains carried an s1/i1/m1 allele, 11 strains carried an s1/i1/m2 allele, and 8 strains carried an s1/i2/m2 allele. By using Fisher's exact test, a statistical association between variations in the cagA and vacA alleles was identified (P ‫؍‬ 0.0007), and by using log linear modeling, this variation was shown to affect the severity of disease outcome (P ‫؍‬ 0.027). Additionally, we present evidence that variation within the middle region of VacA contributes significantly to the distribution of vacA alleles across gender (P ‫؍‬ 0.008) as well as the association with disease outcome (P ‫؍‬ 0.011). In this South Korean population, the majority of H. pylori strains carry the vacA s1/i1/m1 allele and the CagA EPIYA-ABD allele. These facts may contribute to the high incidence of gastric maladies, including gastric cancer.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA

et al. 2010

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“…Helicobacter pylori colonize in the stomach of more than 50% of the world's population and play an essential role in the development of various gastroduodenal diseases (such as gastritis, peptic ulcer, and gastric cancer) (1)(2)(3). Several potential virulence factors such as CagA, VacA, OipA, and HomB have been suggested to play a role in the pathogenesis of organism (4)(5).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran

et al. 2013

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Background: Cytotoxin-associated gene A (CagA)-positive strains of Helicobacter pylori are associated with gastroduodenal diseases. Evidences have suggested that the type of H. pylori CagA EPIYA motifs may be associated with recurrent dyspepsia (i.e. gastritis, peptic ulcer, or gastric cancer). We investigated the prevalence of different EPIYA motifs (A, B, C, or D) in H. pylori strains isolated from patients with recurrent dyspepsia who underwent upper gastrointestinal (GI) endoscopy. We investigated the prevalence of different EPIYA motifs (A, B, C, or D) in H. pylori strains isolated from patients with recurrent dyspepsia who underwent upper gastrointestinal (GI) endoscopy. Materials and Method: H. pylori strains were isolated from biopsy specimens of 220 patients with recurrent dyspepsia. The presence of glmM gene, as a housekeeping gene, CagA gene, and pattern of CagA EPIYA motifs were determined using polymerase chain reaction (PCR) method. The association between the type of motifs and disease state was determined by the Chi-square test, Fisher's exact test, and logistic regression. Results: CagA-positive H. pylori strains were identified in 125 (57%) of patients, including 36 (28.6%) gastritis, 31 (24.6%) duodenal ulcer, and 58 (46.4%) gastric cancer. The frequency of pattern of CagA EPIYA motifs were detected as 39 (31.2%) AB motifs, 54 (43.2%) ABC motifs, 32 (25.6%) ABCC motifs,and no D motifs. The risk of gastric cancer occurrence was estimated to be 2.57 times higher in patients infected by strains with ABCC motif when compared with gastritis and duodenal ulcer patients (p=0.03). Moreover, patients with C-containing motifs were 2.27 times more likely to be afflicted with gastric cancer than with duodenal ulcer. AB motif was more associated with gastritis and duodenal ulcer than ABC and ABCC motifs. Conclusion:The results suggested that CagA-EPIYA ABCC might be associated with gastric cancer, while EPIYA-AB might be associated with duodenal ulcer.

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“…The 3'-end region of cagA where the tyrosine phosphorylation sites are located are highly polymorphic (Covacci et al, 1993;Tummuru et al, 1993;Yamaoka et al, 1998;Yamazaki et al, 2005). Four different CagA EPIYA motifs, EPIYA-A, -B, -C, and -D, have been defined based on the amino acid sequences surrounding the EPIYA residue (Higashi et al, 2002;Jones et al, 2009;Panayotopoulou et al, 2007;Sgouras et al, 2009;Yamazaki et al, 2005). CagA proteins nearly always possess an EPIYA-A and an EPIYA-B, followed by various number of EPIYA-C repeats in Western-type (Yamazaki et al, 2005) or EPIYA-D motifs in East Asian type strains (Panayotopoulou et al, 2007;Sgouras et al, 2009).…”

Section: Introductionmentioning

confidence: 99%

Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA

Karlsson¹,

Ryberg²,

Dehnoei³

et al. 2012

Infection, Genetics and Evolution

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The Helicobacter pylori cagA gene encodes a cytotoxin which is activated by phosphorylation after entering the host epithelial cell. Phosphorylation occurs on specific tyrosine residues within EPIYA motifs in the variable 3'-region. Four different cagA EPIYA motifs have been defined according to the surrounding amino acid sequence; EPIYA-A, -B, -C and -D. Commonly, EPIYA-A and -B are followed by one or more EPIYA-C or -D motif. Due to observed discrepancies in cagA genotypes in cultured H. pylori and the corresponding DNA extracts it has been suggested that genotyping assays preferentially should be performed directly on DNA isolated from biopsy specimens. Gastric biopsies randomly selected from a Swedish cohort were homogenised and used for both direct DNA isolation and for H. pylori specific culturing and subsequent DNA isolation. In 123 of 153 biopsy specimens, the cagA EPIYA genotypes were in agreement with the corresponding cultured H. pylori strains. A higher proportion of mixed cagA EPIYA genotypes were found in the remaining 30 biopsy specimens. Cloning and sequencing of selected cagA EPIYA amplicons revealed variations in number of cagA EPIYA-C motifs in the mixed amplicons. The study demonstrates that culturing of H. pylori introduces a bias in the number of EPIYA-C motif. Consistent with other H. pylori virulence genotyping studies, we suggest that cagA EPIYA analysis should be performed using total DNA isolated from biopsy specimens.funding agencies|Research council in the South-East of Sweden (FORSS)||ALF||Clinical Microbiology, Laboratory Centre-DC, University Hospital, Linkoping, Sweden|

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Polymorphism in the CagA EPIYA Motif Impacts Development of Gastric Cancer

Cited by 120 publications

References 44 publications

Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA

Epidemiological Link between Gastric Disease and Polymorphisms in VacA and CagA

Prevalence of EPIYA motifs in Helicobacter pylori strains isolated from patients with gastroduodenal disorders in northern Iran

Variation in number of cagA EPIYA-C phosphorylation motifs between cultured Helicobacter pylori and biopsy strain DNA

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