Objective. The clinical outcomes of gastric diseases such as chronic gastritis, peptic ulcer, and gastric cancer have been attributed to the interplay of virulence factors of Helicobacter pylori (H. pylori), host genetic susceptibility, and host immune responses. This study investigated the presence of cagA, vacA, iceA2, babA2, and oipA genes and their association with clinical outcomes. Methods. Chronic gastritis, atrophic gastritis, and intestinal metaplasia specimens were obtained from patients who underwent endoscopy and surgical resection between January 2017 and December 2018; specimens from gastric cancer patients treated between January 2014 and December 2018 were also added. H. pylori infection and virulence genes (cagA, vacA, iceA2, babA2, and oipA) were determined using real-time PCR. The association between H. pylori genotypes and clinical outcomes were evaluated using multivariate regression model analysis. The overall survival of gastric cancer patients was compared between genotype combinations. Results. H. pylori was positive in 166 patients with chronic gastritis, precancerous gastric lesions, and gastric cancer. The genes vacA, babA2, and oipA were most prevalent in chronic gastritis (73%), precancerous gastric lesions (62%), and gastric cancer (91%), respectively. The vacA, babA2, and oipA genes were associated with increased risk of gastric cancer (OR = 1.23; 95% CI = 1.13–3.32; P=0.033, OR = 2.64; 95% CI = 1.44–4.82, P=0.024, and OR = 2.79; 95% CI = 1.58–5.41; P=0.031, respectively). Interestingly, H. pylori vacA+/babA2+/oipA+ genotype infection was associated with increased risk of gastric cancer (OR = 3.85, 95% CI = 1.67–5.77, P=0.014). Conclusion. In this present study, we reported on the virulence genes of H. pylori infection to reveal their association with increased risk of chronic gastritis, precancerous gastric lesions, and gastric cancer. Precancerous gastric lesions with H. pylori vacA+/babA2+/oipA+ genotype increased the risk of gastric cancer.
The toll-like receptors (TLRs) mediate the recognition of Helicobacter pylori and initiate the innate immune response to infection. We hypothesized those genetic polymorphisms in the TLR1, TLR2, TLR4, and TLR10 influence bacterial infection, affecting susceptibility H. pylori to disease outcomes. Genomic DNA was extracted and genotypes of TLR1 (rs4833095), TLR2 (rs3804099 and rs3804100), TLR4 (rs10759932), and TLR10 (rs10004195) polymorphism were detected by the TagMan single-nucleotide epolymorphisms genotyping assay using the real-time PCR hybridization probe method. The TLR1 (rs4833095), C allele and the TLR10 (rs10004195), A allele frequency was significantly increased risk in the H. pylori infection group (odds ratio=1.76, 95% confidence interval=1.84–2.15, P=0.01 and odds ratio=1.81, 95% confidence interval=1.18–3.26, P=0.04, respectively). The TLR1 (rs4833095), C allele and TLR10 (rs10004195), A allele are susceptible TLRs polymorphisms in the Thai population. These findings suggest that TLR1 rs4833095 and TLR10 rs10004195 may play crucial roles in H. pylori susceptibility and gastric pathogenesis.
Background: The gold standard diagnosis of H. pylori related gastritis is evidence of bacteria on histopathological examination of gastric mucosa. Our aim was to study the correlation between gastric mucosal morphology and histopathological severity of H. pylori related gastritis. Materials and Methods: Division was made on morphological features into:Type 1, showing regular arrangement of red dots; Type 2, showing cleft-like appearance; Type 3, with a mosaic appearance; and Type 4, having a mosaic appearance with focal or diffuse hyperemia. Results: Types 1 and 2 gastric mucosal morphologies were statistically significant in predicting an H. pylori negative status (137/145, p<0.01), while Types 3 and 4 were significant a positive status (139/155, p<0.01). The sensitivity, specificity, positive and negative predictive values of Type 3 and 4 morphologies for predicting H. pylori positive were 94.6%, 89.5%, 89.7% and 94.5%, respectively, with a good correlation with inflammation grading (p<0.01). Conclusions: Our study suggests that gastric mucosal morphology can be reliably identified using conventional white light source gastroscopy with good correlation between findings and inflammation grading.
To date, no potential markers have been established for predicting prognosis in gastric cancer. Matrix metalloproteinase-7 (MMP-7) has been suggested as a prognostic marker in several cancers. In this study, we aimed to determine the expression of the MMP-7 protein and its polymorphisms in gastric cancer tissues. The association between MMP-7 expression level and clinicopathological characteristics was also evaluated. MMP-7 protein expression and its polymorphisms were investigated in a total of 400 patients using immunohistochemistry and TaqMan SNP genotyping assays. The correlation of MMP-7 expression with clinicopathological characteristics, including tumor location, tumor size, histologic type, lymphatic invasion, vascular invasion, pathological T stage, pathological TNM stage, residual tumor, and CEA level, was investigated. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a multivariate Cox proportional hazards regression model. MMP-7 expression was found in 283 of 400 (70.75%) gastric cancer tissues. Expression of MMP-7 was significantly associated with poor clinicopathological characteristics, including vascular invasion ( OR = 6.61 , 95 % CI = 4.26 – 9.89 , p = 0.024 ), lymphatic invasion ( OR = 8.17 , 95 % CI = 4.47 – 12.39 , p = 0.017 ), undifferentiated histologic type ( OR = 2.46 ; 95% CI, 1.31–4.52; p = 0.014 ), higher TNM stage (stage IV) ( OR = 1.48 , 95 % CI = 1.08 – 3.08 , p = 0.047 ), and high CEA level ( OR = 5.96 , 95 % CI = 2.12 – 8.12 , p = 0.026 ). We further observed a significant association of the variant genotype; gastric cancer patients carrying GG of MMP-7 (-181A/G; rs11568818) had a greater increased risk of MMP-7 expression than did wild-type (WT) carriers (AG: odds ratio OR = 5.67 ; 95 % CI = 1.57 – 7.23 ; p = 0.024 and GG: OR = 8.32 ; 95 % CI = 2.94 – 11.42 ; p = 0.016 ). These findings suggest that MMP-7 expression can be used to predict the prognosis of gastric cancer patients.
Our results indicate that the presence of TLR10 rs10004195, A/T heterozygous, and T/T homozygous genotypes is associated with type 1, 2, and 3 whereas that of the A/A homozygous genotype is associated with type 4 and 5 of gastric mucosal patterns. This suggests that the A/A homozygous genotype contributes to severe inflammation in H. pylori-associated gastritis in Thai patients.
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