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

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