Helicobacter pylori Infection Mediates Transcriptional Alteration of Genes Involved in DNA Damage Response

Abstract

Background: Gastritis is among the most common human diseases worldwide. Although the involvement of Helicobacter pylori infection as a class I human carcinogen for gastric cancer progression is accepted, it is not well known how gastritis progression to atrophy and stomach cancer occurs. In this case-control study, the potential link of H. pylori infection with alteration in the transcription of genes involved in DNA Damage Response pathways was investigated among the patients with gastritis. Methods: To measure the difference in relative mRNA expression level of ATM, CHEK2, TP53, DCLRE1C, POLM, XRCC4 genes between H. pylori infected and non-infected patients, gastric biopsies of 30 H. pylori infected patients with moderate chronic gastritis and 30 non-infected patients with mild chronic gastritis were analyzed. Results: Up-regulation of genes linked to non-homologous end joining (NHEJ) pathway (DCLRE1C, POLM, and XRCC) was shown in 40% (8.44 fold ±13.91), 63.33% (15.72 fold ±33.08) and 50% (9.99 fold ±21.55), respectively, and also to DDR pathway (ATM, CHEK2 and TP53) in 33% (2.42 fold ±3.17), 40% (2.86 fold ±3.61) and 50% (5.00 fold ±6.52), respectively. No correlation was detected among alteration in the transcription level of the studied genes and age or gender.Conclusion: Our results provide new data that may support the potential involvement of H. pylori infection in the activation of genes involved in DNA damage response, mainly through non-homologous end joining DNA repair system that might be linked to mutagenesis in the pre-cancerous gastric tissue.