Gastric atrophy caused by Helicobacter pylori infection was suggested to influence the risk of adenocarcinoma of the esophagogastric junction (AEGJ), however, the evidence remains limited. We aimed to examine the associations of H. pylori infection and gastric atrophy (defined using serum pepsinogen [PG] I to PGII ratio) with AEGJ risk, based on a population-based case-control study in Taixing, China (2010-2014), with 349 histopathologically confirmed AEGJ cases and 1859 controls. We explored the potential effect modification by H. pylori serostatus and sex on the association of serum PGs with AEGJ risk. We used unconditional logistic regression models to estimate odds ratios (ORs) and 95% confidence intervals (CIs). H. pylori seropositivity was associated with an elevated AEGJ risk (OR = 1.95, 95% CI: 1.47-2.63). Neither CagA-positive nor VacA-positive strains dramatically changed this association. Gastric atrophy (PGI/PGII ratio ≤4) was positively associated with AEGJ risk (OR = 2.36, 95% CI: 1.72-3.22). The fully adjusted ORs for AEGJ progressively increased with the increasing levels of PGII (P-trend <.001). H. pylori showed nonsignificant effect modification (P-interaction = .385) on the association of gastric atrophy with AEGJ. In conclusion, H. pylori and gastric atrophy were positively associated with AEGJ risk. These results may contribute evidence to the ongoing research on gastric atrophy-related cancers and guide the prevention and control of AEGJ.

Since treatment options for GC are limited, the best and most effective way is to try to reduce the incidences and understanding prevention strategies.

The success in prevention strategies depends on understanding etiologic mechanisms. Our goal is to identify the major nutritional risk factors for GC, and we will examine the controversial evidence.

We used Pub Med, Google Scholar, Scopus, Science Direct, Elsevier, Springer, and MEDLINE databases for extracting articles.

Human studies published in English from 1997to2018 were included. Two reviewers other than authors initially assessed abstract of 742 papers and 248papers were selected for future assessments. After full review and consideration of the inclusion and exclusion criteria, we used 85 articles.

Dietary salt is a strong independent risk for GC whereas alcohol is most likely a risk only in the presence of heavy alcohol consumption. Red meat and high-fat diet increase the risk of developing GC but fresh fruits, vegetables and certain micronutrients like selenium and vitamin C are protective.

Some nutrients such as selenium, vitamin C, folate, iron, and zinc are involved in the etiology of GC. On the other hand; salt, fats, alcohol, red meat, and pepper were reported to be risk factors for GC. Since the GC is a heterogeneous malignancy and multiple factors are involved in its genesis.

Helicobacter pylori gastritis affects gastric pH and concentrations of ascorbic acid, hydrogen peroxide, hypochlorite, ammonia and urea, pepsin, and mucin. First, the separate effects of each of these altered factors on oxidation of pork were investigated during in vitro gastrointestinal digestion. Lipid and protein oxidation increased (range 23-48%) in duodenal digests of pork previously exposed to elevated (6.1) versus normal acidic stomach pH (2.3 to 3.5) conditions. Salivary nitrite reduced the formation of lipid and protein oxidation products (range 14-20%) under normal acidic but not elevated stomach pH conditions. Higher amounts of hydrogen peroxide and lower amounts of ascorbic acid decreased concentrations of lipid oxidation products in duodenal pork digests, whereas ammonia slightly stimulated protein oxidation during digestion. Second, two H. pylori gastritis-duodenal digestion models were installed using a set of altered compound concentrations at normal acidic or elevated stomach pH. The elevated pH-gastritis-duodenal digestion model increased pork protein oxidation compared with the normal pH-gastritis and the normal digestion model (14.3 ± 2.1 vs 8.2 ± 1.0 nmol DNPH/mg protein, P < 0.001). Compared with the other models, protein oxidation was also increased when nitrite-cured pork was exposed to the elevated pH-gastritis-duodenal digestion model (10.8 ± 1.4 vs 5.9 ± 0.8 nmol DNPH/mg protein, P < 0.001), but no significant effect of the model was observed when the pork was seasoned with herbs. Lipid oxidation was not or was marginally affected by the installed model.

Advances in research techniques have made it possible to map the microbial communities in the gastrointestinal (GI) tract, where the majority of bacteria in the human body reside. Disturbances in these communities are referred to as dysbiosis and have been associated with GI cancers. Although dysbiosis is observed in several GI malignancies, the specific role of these changes has not been understood to the extent of Helicobacter pylori (HP) in gastric cancer (GC). This review will address the bacterial communities along the GI tract, from the oral cavity to the anal canal, particularly focusing on bacterial dysbiosis and carcinogenesis. Just as non-HP bacteria in the stomach may interact with HP in gastric carcinogenesis, the same may hold true for other GI tract malignancies, where an interplay between microbes in carcinogenesis seems conceivable, especially in colorectal cancer (CRC). In the last part of this review we will discuss the potential mechanisms of bacterial dysbiosis in GI carcinogenesis.

To date, gastric carcinoma (GC) is one of the common and fatal digestive malignancies worldwide. The prognosis of GC is not always satisfactory because of late diagnosis. Scholars are keen on discovering novel accurate and economical biomarkers in body liquids for GC screening to detect and evaluate the lesion before the results of imaging techniques are obtained. While traditional serum assays have limited sensitivity and specificity, gastrointestinal juice may provide relevant specific biomarkers because of its close contact with the tumor. Herein, the current progress in the relationship between gastrointestinal fluid analyses and GC is systematically and comprehensively reviewed. The detection of gastric juice pH, fluorescence spectrum, cytology, Helicobacter pylori-associated markers, nitrosamines, conventional tumor markers, amino acids, proteomics, microRNAs, long noncoding RNAs, protein-coding genes, vitamin C, etc., and combination tests of different category markers could provide important diagnostic and prognostic clues for gastrointestinal diseases. Particularly, early GC may be efficiently screened using gastric juice. Gastrointestinal fluid examination could also predict the adverse effects of postgastrectomy, such as pancreatic leakage, fistula, and abscess. Gastric fluid markers should be further studied to reveal the early predicators of malignancy and complications. The methods for obtaining the samples of gastrointestinal juice with minimum incision should also be comprehensively investigated.

Helicobacter pylori (H. pylori) infects the human stomach during infancy and develops into chronic active inflammation. The majority of H. pylori tend to colonize within the mucous gel layer of the stomach. The stomach lacks its own immune function, thus innate immunity as the first line of defense is vital for specific immunity against H. pylori. We review recent discoveries in the pathophysiologic roles of toll-like receptors (TLRs), mainly TLR2 and TLR4, in H. pylori-induced inflammation. In addition, the TLR pathways activated by H. pylori-induced inflammation have been shown to be closely associated not only with gastric carcinogenesis, but also with formation of the tumor microenvironment through the production of pro-inflammatory cytokines, chemokines, and reactive oxygen species. Although the correlation between single nucleotide polymorphisms of TLRs and gastric cancer risk remains unclear, a recent study demonstrated that STAT3-driven up-regulation of TLR2 might promote gastric tumorigenesis independent of inflammation. Further research on the regulation of TLRs in H. pylori-associated gastric carcinogenesis will uncover diagnostic/predictive biomarkers and therapeutic targets for gastric cancer.

To investigate gastric juice nitrate/nitrite concentration according to mucosal surface pH extent (area) of gastric corpus intimately contacting the gastric juice.

We included ninety-nine patients with dyspepsia. To evaluate gastric mucosal surface pH and its extent, gastric chromosocpy was performed by spraying phenol red dye on the corpus mucosa and estimating the extent of area with color changed. Nitrate/nitrite concentrations and pH of gastric juice were measured by ELISA and pH meter, respectively. Silver staining was done to histologically confirm the presence of Helicobacter pylori.

Intragastric nitrate/nitrite concentrations in patients, showing phenol red staining mucosa were higher than those of unstaining mucosa (p=0.001): the more extensive in the area of phenol red staining area of corpus, the higher gastric juice pH found (r=0.692, p<0.001). Furthermore, the intragastric nitrate/nitrite concentrations correlated positively with gastric juice pH (r=0.481, p<0.001).

The changes of mucosal surface pH and its extent in gastric corpus might affect either pH or nitrate/nitrite level of gastric juice.

Soy food is known to contribute greatly to a reduction in the risk of gastric cancer (GC). However, both Japanese and Korean populations have high incidence rates of GC despite the consumption of a wide variety of soy foods. One primary reason is that they consume fermented rather than non-fermented soy foods. In order to assess the varying effects of fermented and non-fermented soy intake on GC risk in these populations, we conducted a meta-analysis of published reports. Twenty studies assessing the effect of the consumption of fermented soy food on GC risk were included, and 17 studies assessing the effect of the consumption of non-fermented soy food on GC risk were included. We found that a high intake of fermented soy foods was significantly associated with an increased risk of GC (odds ratio [OR] = 1.22, 95% confidence interval [CI] = 1.02-1.44, I(2) = 71.48), whereas an increased intake of non-fermented soy foods was significantly associated with a decreased risk of GC (overall summary OR = 0.64, 95% CI = 0.54-0.77, I(2) = 64.27). These findings show that a high level of consumption of non-fermented soy foods, rather than fermented soy foods, is important in reducing GC risk.

Several studies have reported an association between gastric atrophy and upper gastrointestinal cancers. Our aim was to summarise the available information and calculate the relative risks (RRs) associated with gastric atrophy for gastric cardia adenocarcinoma (GCA), oesophageal squamous cell carcinoma (OSCC), and oesophageal adenocarcinoma (OAC) by conducting a systematic review and meta-analysis.

We searched the PubMed and ISI-Web of Science databases, as well as the reference lists of the relevant articles. Summary RRs and 95% confidence intervals (95% CI) were calculated using random-effects models for the association between gastric atrophy, defined histologically or by serum pepsinogen markers, and OSCC, OAC, and GCA.

Eighteen articles were included in the meta-analysis; 13, 7, and 3 studies reported on GCA, OSCC, and OAC, respectively. The overall RRs (95% CI) for the three cancer types were: GCA, 2.89 (2.09-3.98); OSCC, 1.94 (1.48-2.55); OAC, 0.51 (0.19-1.37). Several subgroup analyses showed the robustness of the results. In the majority of the analyses, there was low to moderate heterogeneity.

This study found two- to threefold increased risk of OSCC and GCA but a possible reduced risk of OAC in people with gastric atrophy. Further studies are needed to establish the association with OAC and causal association with OSCC, and mechanisms of the increased risk need to be investigated for GCA.

Few reports have described the cancer prevalence of peptic ulcer patients with long-term follow-up studies. We have conducted a long-term retrospective cohort study of Japanese peptic ulcer patients and evaluated the risk factors for the occurrence of gastric cancer (GCa). A total of 136 patients diagnosed with peptic ulcers from 1975 to 1983 were enrolled. These 136 cases [102 males and 34 females; 69 gastric ulcer (GU) and 67 duodenal ulcer (DU) patients at the time of enrollment; mean follow-up period of 14.4 years (range 1-30 years)] after being matched with a tumour registry database in Hiroshima prefecture were surveyed for GCa. We investigated Helicobacter pylori duodenal ulcer promoter gene A (dupA) using paraffin-embedded gastric biopsy specimens in 56 cases. Gastric acid secretion and basal acid output (BAO) in 40 cases, and maximal acid output in 68 cases, had been measured at first diagnosis of peptic ulcers. GCa was detected in 24 patients (17 with GU, 7 with DU) during the follow-up. The prevalence of GCa was significantly higher in GU patients than in DU patients (log-rank test P<0.05). dupA-positive H. pylori was detected not only in DU patients (9/20) but also in GU patients (9/36). Gastric acid output was significantly larger in quantity in patients with dupA-positive H. pylori than in those with dupA-negative H. pylori (P<0.05). The occurrence of GCa was significantly lower in patients with dupA-positive H. pylori and a high BAO level (log-rank test P<0.05). DUs, higher acid output and dupA-positive H. pylori were negatively associated with GCa.

The gastrointestinal peptide hormone gastrin is responsible for initiating the release of gastric acid in the stomach in response to the presence of food and/or humoral factors such as gastrin releasing peptide. However, it has a role in the growth and maintenance of the gastric epithelium, and has been implicated in the formation and growth of gastric cancers. Hypergastrinemia resulting from atrophic gastritis and pernicious anemia leads to hyperplasia and carcinoid formation in rats, and contributes to tumor formation in humans. Additionally, gastrin has been suspected to play a role in the formation and growth of cancers of the colon, but recent studies have instead implicated gastrin processing intermediates, such as gastrin-17-Gly, acting upon a putative, non-cholecystokinin receptor. This review summarizes the production and chemical structures of gastrin and of the processing intermediate gastrin-17-Gly, as well as their activities in the gastrointestinal tract, particularly the promotion of colon cancers.

It is widely known that vegetable consumption contributes to reducing the risk of gastric cancer (GC). However, the incidence rates of GC remain high in both Japanese and Korean populations, even though they have a high consumption of total vegetables. This may be due to the fact that Japanese and Koreans mainly consume processed vegetables, such as cooked, salted, or pickled vegetables, rather than fresh vegetables. To determine whether the intakes of fresh and pickled vegetables have different effects on the risk of GC in Japanese and Korean populations, we carried out a meta-analysis of published epidemiological reports. Eight studies on the consumption of fresh vegetables and 14 studies on the consumption of pickled vegetables related to GC risk were included in this meta-analysis. Four studies exploring differences in GC risk in men and women were considered separately. We observed that a high intake of fresh vegetables was significantly associated with a decreased risk of GC (overall summary OR = 0.62, 95% CI = 0.46-0.85) but that a high intake of pickled vegetables was significantly associated with an increased risk of GC (overall summary OR = 1.28, 95% CI = 1.06-1.53). The results of this meta-analysis provide evidence that a high intake of pickled vegetables may increase GC risk and suggest that a high consumption of fresh vegetables, rather than a large total amount of vegetables including pickled vegetables, is important to reduce GC risk.

We have previously described a synergistic interaction between hypergastrinemia and Helicobacter felis infection on gastric corpus carcinogenesis in FVB/N mice housed under specific-pathogen-free conditions. However, gastrin-deficient (GAS-KO) mice on a mixed C57BL/6/129Sv genetic background maintained in conventional housing were reported to develop spontaneous gastric antral tumors. Therefore, we investigated the role of gastrin in Helicobacter-associated gastric carcinogenesis in H. felis-infected mice on a uniform C57BL/6 background housed in specific-pathogen-free conditions. Hypergastrinemic transgenic (INS-GAS) mice, GAS-KO mice, and C57BL/6 wild-type mice were infected with H. felis for either 12 or 18 months. At 12 months postinfection, INS-GAS mice had mild corpus dysplasia, while B6 wild-type mice had either severe gastritis or metaplasia, and GAS-KO mice had only mild to moderate gastritis. At 18 months postinfection, both INS-GAS and B6 wild-type mice had both severe atrophic gastritis and corpus dysplasia, while GAS-KO mice had severe gastritis with mild gastric atrophy, but no corpus dysplasia. In contrast, both GAS-KO and B6 wild-type mice had mild to moderate antral dysplasia, while INS-GAS mice did not. H. felis antral colonization remained stable over time among the three groups of mice. These results point to a distinct effect of gastrin on carcinogenesis of both the gastric corpus and antrum, suggesting that gastrin is an essential cofactor for gastric corpus carcinogenesis in C57BL/6 mice.

Gastrin and gastrin receptor-deficient mice have been used for genetic dissection of the role of gastrins in maintaining gastric homeostasis and control of acid secretion. The gastrin knockout mice are achlorhydric due to inactivation of the ECL and parietal cells. Moreover, this achlorhydria is associated with intestinal metaplasia and bacterial overgrowth, which ultimately leads to the development of gastric tumours. The association between progastrin, progastrin-derived processing intermediates and colorectal carcinogenesis has also been examined through genetic or chemical cancer induction in several mouse models, although the clinical relevance of these studies remains unproven. While others have focused on models of increased gastrin production, the present review describes the lessons learned from gastrin-deficient mice. Study of these mice helps our understanding of how dysregulation of gastrin secretion may be implicated in human disease.

We evaluated the topography of histological gastritis, which may be risk factors for gastric cancer (GCa). A total of 530 Helicobacter pylori-positive patients underwent diagnostic upper-gastrointestinal endoscopy. Biopsy specimens were obtained from the gastric antrum and body to assess the grade of gastritis. Subjects were divided into four groups by the topography of active gastritis (antrum predominant gastritis, AP; pan-gastritis with or without corpus atrophy, Pan-1 and Pan-2; and corpus predominant gastritis, CP). A higher prevalence of GCa followed the order of Pan 2-->CP-->Pan 1-->AP. The age of patients decreased in the same order. When we set Pan 2 and CP as a high-risk group, the sensitivity and specificity for GCa detection were 77.3 and 54.7%, which were superior to the serum criteria using pepsinogens. These suggest that topography of histologic gastritis is an important marker to identify the high-risk group.

The objective of this study was to determine whether the intake of nitrate relative to antioxidant vitamin rather than absolute intake of nitrate affects the risk of gastric cancer (GC). In a case-control study in Korea using a food frequency questionnaire, trained dietitians interviewed 136 GC cases and an equal number of controls matched by sex and age. As an index of nitrate intake relative to antioxidant vitamins intake, we calculated the nitrate:antioxidant vitamin consumption ratio. The mean daily nitrate intake from foods was very high in our subjects. Higher absolute intake of nitrate was not associated with GC risk [odds ratios (OR) = 1.13; 95% confidence interval (CI) = 0.42-3.06]. However, the GC risk distinctly increased as the nitrate:antioxidant vitamin consumption ratio increased, particularly with higher nitrate:vitamin E (OR = 2.78; 95% CI = 1.01-7.67) and nitrate:folate ratios (OR = 3.37; 95% CI = 1.28-8.87). Therefore, GC risk was influenced by the intake of nitrate relative to antioxidant vitamins. Our results suggest that a decrease in the intake of nitrate relative to antioxidant vitamins is considerably more effective in reducing GC risk than either a lower absolute intake of nitrate or a higher intake of antioxidant vitamins alone.

Many epidemiological reports indicate that Helicobacter pylori (H pylori) infection plays an important role in gastric carcinogenesis. Several genetic and epigenetic alterations contribute to the initiation, promotion, and progression of the cancer cells in a multi-step manner. H pylori is known to induce chronic inflammation in the gastric mucosa. Its products, including superoxides, participate in the DNA damage followed by initiation, and the inflammation-derived cytokines and growth factors contribute to the promotion of gastric carcinogenesis. By eradicating H pylori, gastric inflammation can be cured; the therapy diminishes the levels not only of inflammatory cell infiltration, but also atrophy/intestinal metaplasia in part. A randomized controlled trial revealed that the eradication therapy diminished the gastric cancer prevalence in cases without pre-cancerous conditions. In addition, recent epidemiological studies from Japanese groups demonstrated that the development of gastric cancer, especially of the intestinal type, was decreased by successful eradication therapy, although these were designed in a non-randomized manner. However, it should be mentioned that endoscopic detection is the only way to evaluate the degree of gastric carcinogenesis. We have reported that the endoscopic and histological morphologies could be modified by eradication therapy and it might contribute to the prevalence of gastric cancer development. Considering the biological nature of cancer cell proliferation, it is considered that a sufficiently long-term follow-up would be essential to discuss the anticancer effect of eradication therapy.