Association of D299G Polymorphism of TLR4 Gene and CagA Virulence Factor of H. pylori among the Iranian Patients with Colorectal Cancer

Background: Colorectal cancer (CRC) represents 9% of all malignancies globally. TLR4 gene defenses against Helicobacter pylori infection (HPI), so its mutations are a risk factor for CRC. As there is a correlation between (HPI) and gastric cancer, we investigated whether there is an association between CagA virulence factor in HPI and D299G polymorphism of TLR4 gene with developing CRC among Iranians. Methods: This retrospective study included 85 biopsies of confirmed colorectal lesions out of 230 subjects, which were divided into two age groups. Single nucleotide polymorphism (SNP) D299G in the TLR4 gene was assessed using Tetra-primer ARMS-PCR. The expression of TLR4 and the CagA virulence factor in H.pylori was assessed using real-time PCR (RT-PCR). Results: Chi-squared test showed genotype frequencies of GG were 79% and 62%in patients 51> and 51<years, respectively. Logistic regression showed a positive association between the presence of CagA and a high GG allele (p=0.002). The odd ratio was predicted as 4.80 using the Hardy-Weinberg equilibrium assumption. Iranians with CagA and high GG of D299G were four times more likely to develop CRC than their peers with AA allele. Conclusion: H. pylori-positive CagA has a higher ability to escape from the immune response. D299G polymorphism of TLR4 gene full of GG allele is an influential risk factor in developing CRC. Hence finding H. pylori-positive CagA should be noticed as a marker of the TLR4 gene full of GG allele in screening plans.