Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy

<i>Helicobacter pylori</i> (<i>Hp</i>) is the major recognized risk factor for non-cardia gastric cancer (GC), but only a fraction of infected subjects develop GC, thus GC risk might reflect other genetic/environmental cofactors and/or differences in virulence among infectiou...

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Main Authors: Sonia Toracchio, Rosario Alberto Caruso, Silvia Perconti, Luciana Rigoli, Enrico Betri, Matteo Neri, Fabio Verginelli, Renato Mariani-Costantini
Format: Article
Language:English
Published: MDPI AG 2020-02-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/8/3/324
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author Sonia Toracchio
Rosario Alberto Caruso
Silvia Perconti
Luciana Rigoli
Enrico Betri
Matteo Neri
Fabio Verginelli
Renato Mariani-Costantini
author_facet Sonia Toracchio
Rosario Alberto Caruso
Silvia Perconti
Luciana Rigoli
Enrico Betri
Matteo Neri
Fabio Verginelli
Renato Mariani-Costantini
author_sort Sonia Toracchio
collection DOAJ
description <i>Helicobacter pylori</i> (<i>Hp</i>) is the major recognized risk factor for non-cardia gastric cancer (GC), but only a fraction of infected subjects develop GC, thus GC risk might reflect other genetic/environmental cofactors and/or differences in virulence among infectious <i>Hp</i> strains. Focusing on a high GC risk area of Northern Italy (Cremona, Lombardy) and using archived paraffin-embedded biopsies, we investigated the associations between the <i>Hp vacA</i> and <i>cagA</i> genotype variants and gastric intraepithelial neoplasia (GIN, 33 cases) versus non-neoplastic gastroduodenal lesions (NNGDLs, 37 cases). The <i>glmM</i> gene and the <i>cagA</i> and <i>vacA</i> (s and m) genotypes were determined by polymerase chain reaction (PCR) and sequencing. <i>Hp</i> was confirmed in 37/37 (100%) NNGDLs and detected in 9/33 GINs (27%), consistently with the well-known <i>Hp</i> loss in GC. <i>CagA</i> was detected in 4/9 <i>Hp</i>-positive GINs and in 29/37 NNGDLs. The <i>vacA</i> s1a and m1 subtypes were more common in GINs than in NNGDLs (6/7 vs. 12/34, p=0.014, for s1a; 7/7 vs. 18/34, p=0.020 for m1), with significant <i>vacA</i> s genotype-specific variance. The GIN-associated <i>vacA</i> s1a sequences clustered together, suggesting that aggressive <i>Hp</i> strains from a unique founder contribute to GC in the high-risk area studied.
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spelling doaj.art-ca79e6af0a504991bdc0b13f10741a472022-12-22T03:46:08ZengMDPI AGMicroorganisms2076-26072020-02-018332410.3390/microorganisms8030324microorganisms8030324Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern ItalySonia Toracchio0Rosario Alberto Caruso1Silvia Perconti2Luciana Rigoli3Enrico Betri4Matteo Neri5Fabio Verginelli6Renato Mariani-Costantini7Center for Advanced Studies (CAST/CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98123 Messina, ItalyCenter for Advanced Studies (CAST/CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyDepartment of Human Pathology in Adult and Developmental Age “Gaetano Barresi”, Section of Pathology, University of Messina, 98123 Messina, ItalyDepartment of Pathology, Istituti Ospitalieri, 26100 Cremona, ItalyCenter for Advanced Studies (CAST/CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyCenter for Advanced Studies (CAST/CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, ItalyCenter for Advanced Studies (CAST/CeSI-MeT), “G. d’Annunzio” University of Chieti-Pescara, 66100 Chieti, Italy<i>Helicobacter pylori</i> (<i>Hp</i>) is the major recognized risk factor for non-cardia gastric cancer (GC), but only a fraction of infected subjects develop GC, thus GC risk might reflect other genetic/environmental cofactors and/or differences in virulence among infectious <i>Hp</i> strains. Focusing on a high GC risk area of Northern Italy (Cremona, Lombardy) and using archived paraffin-embedded biopsies, we investigated the associations between the <i>Hp vacA</i> and <i>cagA</i> genotype variants and gastric intraepithelial neoplasia (GIN, 33 cases) versus non-neoplastic gastroduodenal lesions (NNGDLs, 37 cases). The <i>glmM</i> gene and the <i>cagA</i> and <i>vacA</i> (s and m) genotypes were determined by polymerase chain reaction (PCR) and sequencing. <i>Hp</i> was confirmed in 37/37 (100%) NNGDLs and detected in 9/33 GINs (27%), consistently with the well-known <i>Hp</i> loss in GC. <i>CagA</i> was detected in 4/9 <i>Hp</i>-positive GINs and in 29/37 NNGDLs. The <i>vacA</i> s1a and m1 subtypes were more common in GINs than in NNGDLs (6/7 vs. 12/34, p=0.014, for s1a; 7/7 vs. 18/34, p=0.020 for m1), with significant <i>vacA</i> s genotype-specific variance. The GIN-associated <i>vacA</i> s1a sequences clustered together, suggesting that aggressive <i>Hp</i> strains from a unique founder contribute to GC in the high-risk area studied.https://www.mdpi.com/2076-2607/8/3/324<i>helicobacter pylori</i>virulence factorspathogenicityphylogenetic diversitygastric intraepithelial neoplasiaitaly
spellingShingle Sonia Toracchio
Rosario Alberto Caruso
Silvia Perconti
Luciana Rigoli
Enrico Betri
Matteo Neri
Fabio Verginelli
Renato Mariani-Costantini
Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
Microorganisms
<i>helicobacter pylori</i>
virulence factors
pathogenicity
phylogenetic diversity
gastric intraepithelial neoplasia
italy
title Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
title_full Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
title_fullStr Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
title_full_unstemmed Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
title_short Evolutionarily-Related <i>Helicobacter pylori</i> Genotypes and Gastric Intraepithelial Neoplasia in a High-Risk Area of Northern Italy
title_sort evolutionarily related i helicobacter pylori i genotypes and gastric intraepithelial neoplasia in a high risk area of northern italy
topic <i>helicobacter pylori</i>
virulence factors
pathogenicity
phylogenetic diversity
gastric intraepithelial neoplasia
italy
url https://www.mdpi.com/2076-2607/8/3/324
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