The Role of Helicobacter pylori Virulence Factors in Developing Stomach Cancer: A Review

Abstract

Gastric cancer is one of the leading causes of cancer death worldwide. About 80% or more gastric cancers are stirring by infection with Helicobacter pylori bacterium. Prevalence of H pylori infection in developing countries remains relatively constant; it is rapidly declining in the industrialized world and considerably higher in western countries, The genetic heterogeneity is possibly an adaptation of H. pylori to the gastric conditions of its host. Genetic heterogeneity is thought to occur via several methods of DNA rearrangement and the introduction and deletion of foreign sequences. Diversity is also seen at the nucleotide level via several mechanisms, including transcriptional and translational phase variation and mutation. The 2 genetic loci principally linked with virulence that has been most studied are the cag locus (cag pathogenicity island) and the vacA (vacuolating cytotoxin) gene. The portion of vakA that exhibits maximum diversity in an 800-bp “mid region”, can be phylogenetically divided into two families of alleles, termed m1 and m2. In particular, the "signal region", discloses striking diversity between strains and have two main allelic families, termed s1 and s2, and the s1 type can be further subdivided into s1a, s1b, and s1c. As a result of extensive recombination among vacA alleles, all combinations of signal and mid regions can theoretically arise (s1a / m1, s1b / m1, s1c / m1, s1a / m2, etc). Additionally many adhesins and outer membrane proteins have their putative role in the pathogenesis of H pylori infection. They are BabA (HopS), OipA (HopH), SabA (HopP), iceA, hp0638 gene, AlpA, AlpB, HP-NAP, plasticity region, DupA and lipopolysaccharide. Infection with H pylori strains containing babA2, cagA, and vacA S1 confers the highest risk of gastric cancer.