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

Abstract

Helicobacter pylori (Hp) 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 Hp 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 Hp vacA and cagA genotype variants and gastric intraepithelial neoplasia (GIN, 33 cases) versus non-neoplastic gastroduodenal lesions (NNGDLs, 37 cases). The glmM gene and the cagA and vacA (s and m) genotypes were determined by polymerase chain reaction (PCR) and sequencing. Hp was confirmed in 37/37 (100%) NNGDLs and detected in 9/33 GINs (27%), consistently with the well-known Hp loss in GC. CagA was detected in 4/9 Hp-positive GINs and in 29/37 NNGDLs. The vacA 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 vacA s genotype-specific variance. The GIN-associated vacA s1a sequences clustered together, suggesting that aggressive Hp strains from a unique founder contribute to GC in the high-risk area studied.

Changes in the tissue elements of the gastric mucosa interacting with different strains of <i>Helicobacter pylori</i>, taking into consideration the patient’s genotype

“…H. pylori strains are characterized by marked genetic heterogeneity, which may result in various clinical consequences of the persistence of these bacteria [ 16 ]. Most people infected with H. pylori have no clinical manifestations of infection [ 17 ].…”

“…The peculiarities of the genetic structure of an infectious agent may significantly affect the nature of changes in the mucosa of the upper gastrointestinal tract. As a result, they may affect the development, course, and prognosis of gastric diseases, as well as the effectiveness of therapy [ 14 , 15 , 16 ]. This demonstrates the importance of studying the genetic structure of H. pylori in helicobacter-associated diseases of the stomach and duodenum.…”

Helicobacter pylori in Native Americans in Northern Arizona

“…A 349-bp product indicated presence of cagA . To determine the variability in the EPIYA domains, the 3′ variable region was amplified using primers cag2 and cag4 resulting in products of 550-850-bp [ 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 ]. The PCR reaction mix consisted of 1.7 mM MgCl 2 , 0.2 mM dNTPs, 1 U of Platinum ® Taq DNA polymerase (Invitrogen, Carlsbad, CA, USA), and 300 ng of total DNA in a total volume of 25 μL.…”

Histopathological Features of Helicobacter pylori Infection in Gastric Mucosa

“…31 Intraepithelial neoplasia requires a three or six-month period of close follow-up or ESD. 32 This study found that atrophy of the gastric mucosa caused by Hp infection could be divided into five stages as follows: glandular atrophy of the lamina propria, compensatory proliferative atrophy, intestinal metaplasia atrophy, smooth muscle proliferative atrophy, and proliferative zone atrophy. Accordingly, the histopathological characteristics of atrophy at each stage were studied along with the immunophenotypic characteristics.…”