Etiology Of Gastric Cancer Research Articles

Causal relationship between thyroid dysfunction and gastric cancer: a two-sample Mendelian randomization study.

Gastric cancer is one of the most common cancers worldwide, and its development is associated with a variety of factors. Previous observational studies have reported that thyroid dysfunction is associated with the development of gastric cancer. However, the exact relationship between the two is currently unclear. We used a two-sample Mendelian randomization (MR) study to reveal the causal relationship between thyroid dysfunction and gastric cancer for future clinical work. This study is based on a two-sample Mendelian randomization design, and all data are from public GWAS databases. We selected hyperthyroidism, hypothyroidism, free thyroxine (FT4), and thyroid-stimulating hormone (TSH) as exposures, with gastric cancer as the outcome. We used three statistical methods, namely Inverse-variance weighted (IVW), MR-Egger, and weighted median, to assess the causal relationship between thyroid dysfunction and gastric cancer. The Cochran's Q test was used to assess the heterogeneity among SNPs in the IVW analysis results, and MR-PRESSO was employed to identify and remove IVs with heterogeneity from the analysis results. MR-Egger is a weighted linear regression model, and the magnitude of its intercept can be used to assess the horizontal pleiotropy among IVs. Finally, the data were visualized through the leave-one-out sensitivity test to evaluate the influence of individual SNPs on the overall causal effect. Funnel plots were used to assess the symmetry of the selected SNPs, forest plots were used to evaluate the confidence and heterogeneity of the incidental estimates, and scatter plots were used to assess the exposure-outcome relationship. All results were expressed as odds ratios (OR) and 95% confidence intervals (95% CI). P<0.05 represents statistical significance. According to IVW analysis, there was a causal relationship between hypothyroidism and gastric cancer, and hypothyroidism could reduce the risk of gastric cancer (OR=0.936 (95% CI:0.893-0.980), P=0.006).This means that having hypothyroidism is a protective factor against stomach cancer. This finding suggests that hypothyroidism may be associated with a reduced risk of gastric cancer.Meanwhile, there was no causal relationship between hyperthyroidism, FT4, and TSH and gastric cancer. In this study, we found a causal relationship between hypothyroidism and gastric cancer with the help of a two-sample Mendelian randomisation study, and hypothyroidism may be associated with a reduced risk of gastric cancer, however, the exact mechanism is still unclear. This finding provides a new idea for the study of the etiology and pathogenesis of gastric cancer, and our results need to be further confirmed by more basic experiments in the future.

The viral etiology of EBV-associated gastric cancers contributes to their unique pathology, clinical outcomes, treatment responses and immune landscape.

Epstein-Barr virus (EBV) is a pathogen known to cause a number of malignancies, often taking years for them to develop after primary infection. EBV-associated gastric cancer (EBVaGC) is one such malignancy, and is an immunologically, molecularly and pathologically distinct entity from EBV-negative gastric cancer (EBVnGC). In comparison with EBVnGCs, EBVaGCs overexpress a number of immune regulatory genes to help form an immunosuppressive tumor microenvironment (TME), have improved prognosis, and overall have an "immune-hot" phenotype. This review provides an overview of the histopathology, clinical features and clinical outcomes of EBVaGCs. We also summarize the differences between the TMEs of EBVaGCs and EBVnGCs, which includes significant differences in cell composition and immune infiltration. A list of available EBVaGC and EBVnGC gene expression datasets and computational tools are also provided within this review. Finally, an overview is provided of the various chemo- and immuno-therapeutics available in treating gastric cancers (GCs), with a focus on EBVaGCs.

The role of metal ions in the occurrence, progression, drug resistance, and biological characteristics of gastric cancer.

Metal ions exert pivotal functions within the human body, encompassing essential roles in upholding cell structure, gene expression regulation, and catalytic enzyme activity. Additionally, they significantly influence various pathways implicated in divergent mechanisms of cell death. Among the prevailing malignant tumors of the digestive tract worldwide, gastric cancer stands prominent, exhibiting persistent high mortality rates. A compelling body of evidence reveals conspicuous ion irregularities in tumor tissues, encompassing gastric cancer. Notably, metal ions have been observed to elicit distinct contributions to the progression, drug resistance, and biological attributes of gastric cancer. This review consolidates pertinent literature on the involvement of metal ions in the etiology and advancement of gastric cancer. Particular attention is directed towards metal ions, namely, Na, K, Mg, Ca, Fe, Cu, Zn, and Mn, elucidating their roles in the initiation and progression of gastric cancer, cellular demise processes, drug resistance phenomena, and therapeutic approaches.

Study of epidemiological Helicobacter pylori infection among Iraqi patients

Background: Helicobacter pylori (H. pylori) continues to be a highly prevalent chronic infection on a global scale. Despite an apparent rise in prevalence across numerous countries globally, H.pylori continues to be a significant determinant in the etiology of peptic ulcer disease, gastric cancer, and dyspeptic symptoms. Objectives: To determine the prevalence of H.pylori infection in Baghdad province, Iraq. Patients and methods: This prevalence study was conducted in Baghdad province from March 2019 to March 2023. 240 participants were divided into 120 males and 120 females, all participants suffered from a disorder in the gastrointestinal tract. The presence of H.pylori was identified using the Urea breath test method, a standard procedure employed to diagnose H.pylori or validate the elimination of the pathogen from patients following H.pylori treatment. Results: The research findings indicate that the prevalence of H.pylori infection differs between genders, with females having a higher incidence rate (29.2%) than males (22.5%). The study shows the level of education does not decrease the percentage of infection and the percentage of infected persons in non-literate was (11.6 % ), the secondary level was ( 14.1 % ) and in academic level person ( 22.9 % ). The study shows the age effect on the percentage of infection, in patients aged less than 20 years old the percentage was (7.9 % ), in patients between 21 – and 40 years old the percentage was ( 30.4 % ) which is considered a high percentage, and in age more than 40 years old the percentage decreased to (11.6 %). Conclusion: In conclusion, the study H.pylori infection is influenced by gender, with a greater frequency of infection seen in females. The level of education did not decrease the percentage of infection. The percentage of infection affected by age and the higher percentage the age between (21–and 40) was considered a higher age for infection.

Frequency, distribution and determinants of Helicobacter pylori infection in adults and adolescents with gastric symptoms: cross-sectional epidemiological inquiry in district Haripur, Pakistan.

Helicobacter pylori (HP) is a vital element in the etiology of peptic ulcers and gastric cancer. This research aimed to determine the frequency, distribution, and determinants of HP infection in adults and adolescents with gastric symptoms in district Haripur, Khyber Pakhtunkhwa, Pakistan. This cross-sectional study was performed from June 2018 to June 2020 at the Medical Laboratory Technology Department, The University of Haripur, Pakistan. Presence of HP was a research variable, while sex, age groups, education status, overcrowding, dining habits, milk intake, drinking water source and animal contact were grouping variables. Immuno-chromatographic technique (ICT) was used to for serological detection of HP antibodies. All variables were represented by frequency and percentage with 95%CI. Prevalence of HP and its distribution by eight socio-demographic variables was testified by the chi-square goodness-of-fit test while association was testified by chi-square test of association. Out of total 1160 cases, 557 (48%) were positive for HP. Population prevalence was higher in men, in the age group 20-40 years, illiterate, family size ≤ 10 persons, taking restaurant food, using tetra pack, using municipal water, and having animal contact. The observed prevalence of HP was similar to its expected prevalence in the population. The observed distribution of HP in the sample was different from its expected distribution in population by eight socio-demographic variables. Presence of HP was associated with all eight socio-demographic variables besides age groups.

Does leptin cause proximal gastric cancer in the obese? The role of serum leptin in the etiology of proximal gastric cancer.

The aim of the present study was to determine the correlation between obesity, serum levels of leptin and proximal gastric cancer. Sixty-four gastric cancer patients operated on with curative intent were included in the study. We determined the correlation between the preoperative serum levels of leptin and the tumor's location. Serum leptin levels were correlated significantly with the proximal third location (p=0.04), gastric outlet obstructing tumors (p<0.0001), CRP levels (p=0.03) and BMI (p<0.0001). Patients with high serum levels of leptin had significantly more intestinal types of gastric cancer (p=0.033) and better differentiation (p=0.009). The linear regression model determined the proximal tumor location (beta: 0.467; p=0.045), BMI (beta: 0.657; p=0.001), high preoperative serum albumin (beta: 0.563; p=0.016) and the presence of pyloric stenosis (beta: 0.525; p=0.006) as related significantly to serum leptin levels. The Cox proportional hazard model identified age (HR: 0.003; 95 % CI: 0-0.794; p=0.041), preoperative serum levels of leptin (HR: 0.125; 95 % CI: 0.018-0.887; p=0.037) and the number of extracted LNs (HR: 0.001; 95 % CI: 0-0.677; p=0.038) as independent prognostic factors. Serum levels of leptin were significantly elevated in patients with proximal gastric cancer, suggesting that the leptin's effect might be due to its systemic secretion. This might explain the higher incidence of proximal gastric cancer in obese patients. Elevated serum leptin levels were an independent prognostic factor.

Mental Health Conditions, Including Depression and Stress, Are Associated with Increased Odds of Gastric Cancer—Insights into the Role of Diet: A Case-Control Study

Several risk factors, including nutritional/lifestyle ones, play a role in gastric cancer etiology. Further interactions with mental health have also been emphasized. We hypothesized that individuals with mental disorders would exhibit compromised nutrient intake, increasing their risk of gastric cancer. The state of mental health was evaluated in 82 patients with gastric cancer and 95 healthy controls using the 21-item Depression–Anxiety–Stress Scale. The participants’ dietary intakes were evaluated by a 168-item food frequency questionnaire. Based on fully adjusted logistic regressions, there was a significant association between depression (OR = 1.938, CI 95%: 1.009–3.723) and stress (OR = 2.630, CI 95%: 1.014–6.819) with increased odds of gastric cancer. According to fully adjusted multinomial regressions, vitamins A and B6, beta-carotene, and black tea decreased the odds of depression, based on comparing the control group with cases of depression, while sugar and salt increased its odds. The highest significant association was found for salt intake and anxiety in cases with present anxiety (OR = 4.899, 95% CI: 2.218–10.819), and the highest significant protective effect was found for vitamin B6 and depression in cases with present depression (OR = 0.132, 95% CI: 0.055–0.320). However, considering causal relationships and clarifying the underlying mechanisms is imperative and requires further investigation. Advising healthy dietary patterns, e.g., a Mediterranean diet rich in vitamins, minerals, and phytochemicals such as vitamin A, B6, beta-carotene, and fiber, is expected to reduce the odds of gastric cancer, possibly related to lower levels of anxiety and depression.

Laparoscopic prophylactic total gastrectomy with limited lymphadenectomy for CDH1 gene carriers.

CDH1 gene mutations are the leading etiology of hereditary diffuse gastric cancer with cumulative lifetime risk ranging up to 83%. Prophylactic total gastrectomy (PTG) is, therefore, recommended for CDH1 carriers. A laparoscopic approach may reduce operative risk versus an open operation, thus leading more patients with CDH1 mutations to pursue PTG prior to cancer development. However, more experience and oncologic outcome data are needed for a laparoscopic approach and indicated lymphadenectomy. A retrospective descriptive cohort study of adult patients with CDH1 mutations who underwent laparoscopic PTG with D1 lymphadenectomy between 2012 and 2022 was conducted at a single institution. All patients had preoperative EGD screening, and those with visible tumor lesions on surveillance EGD were excluded and not considered prophylactic. Demographics, family history, pathology, and operative course were obtained. Outcomes included complications, readmission, and postoperative weight change. Among 23 patients, median age was 48years (IQR 37, 53) and 15 (65%) were female. Family history for gastric and/or lobular breast cancer was present in 22 (96%) patients. The median [IQR] time from positive genetic testing to PTG was 347days [140, 625]. Pathologic evaluation showed five (22%) patients with foci of gastric cancer on pre-operative EGD biopsies, 10 (44%) in resected stomach specimens. All lymph nodes were negative. To address early postoperative complications, EJ anastomotic technique changed from EEA to GIA over the course of the study and feeding jejunostomy was no longer placed during PTG with minimal change in postoperative weight loss. This is the largest series, spanning 10years at a single institution, dedicated solely to a laparoscopic approach for risk-reducing PTG. A laparoscopic approach with limited lymphadenectomy resulted in acceptable surgical and oncologic outcomes. Despite no visible cancer, over half of our patients had foci of early gastric cancer. Therefore, CDH1 carriers should consider laparoscopic PTG.

Association between Socioeconomic Factors and the Risk of Gastric Cancer Incidence: Results from an Ecological Study.

Gastric cancer (GC), one of the most common cancer worldwide, remains the third leading cause of cancer-related mortality. The etiology of GC may arise from genetic and environmental factors. This study aimed to determine the association between GC incidence and socioeconomic status in Iran. An ecological study was designed to investigate the relationship between socioeconomic factors and the risk of GC incidence. The data of socioeconomic variables such as income changes, unemployment rate, urbanization ratio, inflation rate, and air pollution changes in 31 provinces were collected from the Statistical Center of Iran, and the data of GC of 31 provinces were provided from the Iranian National Population-based Cancer Registry (INPCR). Data from 2014 to 2017 was analyzed using panel data analysis, the fixed effects model by EViews software. Panel data model was suitable for the present study. Results showed that there was a positive and significant relationship between GC incidence and socioeconomic factors including income changes (P≤ 0.001), unemployment rate (P≤0.01), inflation rate (P≤ 0.05), and air pollution changes (P≤ 0.001). The urbanization ratio showed a negative relationship and was not statistically associated with GC incidence (P> 0.05). Our findings suggest a positive and significant association between socioeconomic status and GC incidence, proposing a GC risk factor. The key public health policies and welfare policies' priority should therefore be to schedule for the GC management.

Role of flavonoids in digestive tract cancer prevention - a review article

Introduction: Flavonoids are bioactive chemical compounds crucial for the functioning of plant organisms. Recently, they have been intensively studied in search of their potential application in medicine. One of the most popular fields in that regard is oncology. Digestive tract cancers are still a challenge for contemporary medicine. Our diet seems to have a direct impact on the etiology of colorectal, gastric, and esophageal cancers. The relationship between the consumption of flavonoids, their specific fractions, and digestive tract cancer morbidity is nowadays frequently investigated.Purpose: This review article aims to discuss the most recent scientific reports and summarize the current state of knowledge, considering the role of flavonoids in digestive tract cancer prevention.Materials and methods: Our work is based on articles accessed through medical information databases (Google Scholar, PubMed, CrossRef), various scientific books, and official NFZ and WHO-certified sites.Results: Total flavonoid intake lowers gastric and esophageal cancer morbidity. A high amount of dietary catechins prevents the growth of gastric and colorectal cancer. Increased consumption of anthocyanidins, flavones, and flavanones decreases esophageal cancer morbidity. Isoflavones, procyanidines, anthocyanidins, flaonols, and flavones severely decrease the chance of developing colorectal cancer.Conclusions: Flavonoids can play an important role in digestive tract cancer prevention. They suppress the growth of colorectal, gastric, and esophageal cancers. Nevertheless, new, high-quality studies are needed in order to compile adequate procedures and bring new, potential drugs to the market.

Bacterial Infections and Cancer: Exploring This Association And Its Implications for Cancer Patients

Bacterial infections are common in the etiology of human diseases owing to the ubiquity of bacteria. Such infections promote the development of periodontal disease, bacterial pneumonia, typhoid, acute gastroenteritis, and diarrhea in susceptible hosts. These diseases may be resolved using antibiotics/antimicrobial therapy in some hosts. However, other hosts may be unable to eliminate the bacteria, allowing them to persist for long durations and significantly increasing the carrier's risk of developing cancer over time. Indeed, infectious pathogens are modifiable cancer risk factors, and through this comprehensive review, we highlight the complex relationship between bacterial infections and the development of several cancer types. For this review, searches were performed on the PubMed, Embase, and Web of Science databases encompassing the entirety of 2022. Based on our investigation, we found several critical associations, of which some are causative: Porphyromonas gingivalis and Fusobacterium nucleatum are associated with periodontal disease, Salmonella spp., Clostridium perfringens, Escherichia coli, Campylobacter spp., and Shigella are associated with gastroenteritis. Helicobacter pylori infection is implicated in the etiology of gastric cancer, and persistent Chlamydia infections present a risk factor for the development of cervical carcinoma, especially in patients with the human papillomavirus (HPV) coinfection. Salmonella typhi infections are linked with gallbladder cancer, and Chlamydia pneumoniae infection is implicated in lung cancer, etc. This knowledge helps identify the adaptation strategies used by bacteria to evade antibiotic/antimicrobial therapy. The article also sheds light on the role of antibiotics in cancer treatment, the consequences of their use, and strategies for limiting antibiotic resistance. Finally, the dual role of bacteria in cancer development as well as in cancer therapy is briefly discussed, as this is an area that may help to facilitate the development of novel microbe-based therapeutics as a means of securing improved outcomes.

Association of Helicobacter Pylori in Carcinoma Stomach at Maharaja Krishna Chandra Gajapat Medical College: A Prospective Study.

Introduction Gastric cancer is the fourth most common type of cancer and the second leading cause of cancer-related death in the world. The etiology of gastric cancer includes Helicobacter pylori infection, diet, lifestyle, tobacco, alcohol, and genetic susceptibility. Upper gastrointestinal endoscopy (UGIE) is the most effective method for examining the upper gastrointestinal tract as compared to the other examination tools. Objective To study the histopathological finding of upper gastrointestinal endoscopic biopsies and its association with H. pylori in cases of carcinoma stomach. Materials and methods This was a hospital-based observational study carried out in the Department of Surgery, at Maharaja Krushna Chandra Gajapati Medical College, Berhampur, a tertiary care hospital in Eastern India. Study population consisted of 106 patients for a period of 2 years from July 2019 to June 2021, after due consideration of the inclusion and exclusion criteria. Endoscopic location and pathological types of the gastric lesion were noted, and all biopsy specimens were investigated to see the presence of H. pylori by rapid urease test (RUT) and histological examination in the form of Giemsa and H&E stain. Results In the present study of 106 cases, 62 cases (58.49%) were found to be positive for H. Pylori by RUT and 72 cases (67.92%) were positive for H. pylori by smear staining. In histopathological study, 72 cases (67.92%) were of intestinal type of carcinoma and 34 cases (32.07%) were of diffuse type of carcinoma. Smear for H . pylori was positive in 56 cases (77.78%) among the 72 cases of intestinal type of carcinoma stomach. Whereas only 16 cases (47.05%) were found to be smear-positive for H. pylori among the 34 cases of diffuse type of lesion. Irrespective of histological type, H. pylori was positive in 67.92% of patients with carcinoma stomach. This association was statistically significant (p<0.001) and indicates its role in intestinal type of gastric carcinoma. Conclusion There is a high frequency of H. pylori infection in cases of stomach cancer. This study confirmed the higher association of H. pylori infection with gastric cancer. Its association with the intestinal histological variety of stomach cancer is more common than diffuse type. The prevalence of H. pylori infection in distal stomach carcinoma is higher than proximal.

Panel of serum biomarkers (GastroPanel) in diagnosis of atrophic gastritis and Helicobacter pylori infection: a protocol of systematic review and meta-analysis

IntroductionThe aetiology of gastric cancer is still unclear but Helicobacter pylori (HP) infection and chronic atrophic gastritis (AG) are recognised as two major risk factors for gastric cancer. GastroPanel (GP)...

Chronic restraint stress promotes gastric epithelial malignant transformation by activating the Akt/p53 signaling pathway via ADRB2.

The etiology of gastric cancer is associated with infectious, environmental and dietary factors, as well as genetic background. Additionally, emerging evidence has supported the vital role of chronic emotional stress on gastric carcinogenesis; however, the underlying mechanism remains unclear. The present study aimed to investigate the effects of chronic stress and a detrimental diet on gastric malignant epithelial transformation in rats. Therefore, 26 Wistar rats were randomly divided into the following four groups: i) Control; ii) detrimental diet (DD); iii) detrimental diet with chronic restraint (DR) and iv) detrimental diet with chronic restraint and propranolol treatment (DRP). ELISA was performed to detect the serum levels of epinephrine and norepinephrine. Epithelial cell apoptosis was analyzed using the TUNEL assay. The mRNA and protein expression levels of Akt and p53 were detected using reverse transcription quantitative PCR and western blotting, respectively. Pathological changes were analyzed using hematoxylin and eosin staining (H&E). The H&E staining results showed that dysplasia in the gastric mucosa occurred in two of eight rats in the DD group and in four of five rats in the DR group, whereas no dysplasia was detected in the DRP group. The apoptotic ratios of gastric epithelial cells were significantly decreased in all treatment groups compared with the control group. Adrenoceptor β2 (ADRB2) protein expression levels were increased significantly only in the DR group and this effect was significantly reduced in the DRP group. The mRNA expression levels of Akt and p53 were significantly upregulated in the DD group, and Akt mRNA expression was further elevated in the DR group. With regard to protein expression, the levels of Akt and p-Akt were significantly increased in the DR group, whereas these effects were reversed in the DRP group. Furthermore, the ratio of p-p53/p53 protein was significantly reduced in the DD or DR groups, but was reversed in the DRP group. Collectively, the findings of the present study suggested that chronic restraint stress potentially aggravates the gastric epithelial malignant transformation induced by a detrimental diet, at least partially via the Akt/p53 signaling pathway mediated via ADRB2.

Reducing the Risk of Gastric Cancer Through Proper Nutrition – A Meta-Analysis

Abstract— Data Sources: Articles for this paper were sourced from PubMed and Google Scholar databases. Data Extraction: Human studies published in English from 2015 to 2021 were included. Two reviewers initially assessed abstracts of 958 papers and 192 papers were selected for future assessments. After a full review, 38 articles were selected. Results: Dietary salt is a high-risk factor for Gastric Cancer (GC) while red meat and a high-fat diet increase the risk. Alcohol intake is only a risk if consumed heavily.&#x0D; Conclusion: Dairy foods, vitamin C, smoked food, rich food, and Helicobacter pylori are included in the etiology of GC. So are fresh fruits, vegetables, and specific refined grains. Salt, fats, spicy foods, alcohol, red meat, and pepper increase the risk. Knowing cancer patients' nutrition problems would help intervention measures be taken to remedy the situation.

Co-infection relationship with Epstein-Barr virus in gastroduodenal diseases with Helicobacter Pylori. Quantitative PCR and EBNA-1 gene-based approach.

Helicobacter pylori (Hp) and Epstein-Barr virus (EBV) are involved in gastric cancer (GC) etiology. EBV/Hp co- infection was thought synergistically increase gastroduodenal disease occurence. We aimed to determine the presence of EBV/Hp co-infection in gastroduodenal diseases. The study group had 68 Hp (+) cases [25 GC, 13 IM (intestinal metaplasia), 30 PU (peptic ulcer)], and the control group had 40 NUD (non-ulcer dyspepsia) cases [20 Hp+, 20 Hp-]. EBV-DNA was detected by non-polymorphic EBNA-1 gene-based qPCR. EBV/EBNA-1 IgG levels were determined by quantitative and qualitative ELISA methods, respectively. EBV-DNA positivity was 32% (8/25), 6.6% (2/30) and 5% (1/20) in GC, PU and NUD Hp (+) cases, respectively. There was a significant difference (p = 0.001) between GC (32%) and NUD Hp (+) (5%) cases in terms of EBV-DNA positivity. Mean EBV-DNA copy numbers were 6568.54 ± 20351, 30.60 ± 159.88 and 13.85 ± 61.93 for GC, PU, and NUD, respectively. In terms of the mean EBV-DNA copy number, a significant difference was found between the groups (p = 0.005). In terms of EBV/EBNA-1 IgG antibody positivity, no significant difference was found between GC and NUD cases (p = 0.248). EBV DNA positivity was found to be significant (odds ration [OR] = 26.71 (p=0.009, %95CI 2.286- 312.041) in multivariate logistic regression. Although we had a small number of GC cases, it can be suggested that the estimated risk created by the synergistic effect based on the addition of EBV increased 26 times in the presence of Hp in GC.

Induction of Fibroblast Growth Factor Receptor 4 by Helicobacter pylori via Signal Transducer and Activator of Transcription 3 With a Feedforward Activation Loop Involving SRC Signaling in Gastric Cancer

Helicobacter pylori (H pylori) infection is the main risk factor for gastric cancer. The role of fibroblast growth factor receptors (FGRFs) in H pylori-mediated gastric tumorigenesis remains largely unknown. This study investigated the molecular and mechanistic links between H pylori, inflammation, and FGFR4 in gastric cancer. Cell lines, human and mouse gastric tissue samples, and gastric organoids models were implemented. Infection with H pylori was performed using invitro and invivo models. Western blot, real-time quantitative reverse-transcription polymerase chain reaction, flow cytometry, immunofluorescence, immunohistochemistry, chromatin immunoprecipitation, and luciferase reporter assays were used for molecular, mechanistic, and functional studies. Analysis of FGFR family members using The Cancer Genome Atlas data, followed by validation, indicated that FGFR4 messenger (m)RNA was the most significantly overexpressed member in human gastric cancer tissue samples (P < .001). We also detected high levels of Fgfr4 mRNA and protein in gastric dysplasia and adenocarcinoma lesions in mouse models. Infection with J166, 7.13, and PMSS1 cytotoxin-associated gene A (CagA)+ H pylori strains induced FGFR4 mRNA and protein expression in invitro and invivo models. This was associated with a concordant activation of signal transducer and activator of transcription 3 (STAT3). Analysis of the FGFR4 promoter suggested several putative binding sites for STAT3. Using chromatin immunoprecipitation assay and an FGFR-promoter luciferase reporter containing putative STAT3 binding sites and their mutants, we confirmed a direct functional binding of STAT3 on the FGFR4 promoter. Mechanistically, we also discovered a feedforward activation loop between FGFR4 and STAT3 where the fibroblast growth factor 19-FGFR4 axis played an essential role in activating STAT3 in a steroid receptor coactivator-dependent manner. Functionally, we found that FGFR4 protected against H pylori-induced DNA damage and cell death. Our findings demonstrated a link between infection, inflammation, and FGFR4 activation, where a feedforward activation loop between FGFR4 and STAT3 is established via steroid receptor coactivator in response to H pylori infection. Given the relevance of FGFR4 to the etiology and biology of gastric cancer, we propose FGFR4 as a druggable molecular vulnerability that can be tested in patients with gastric cancer.

Gastric intestinal metaplasia: Long-term follow-up results.

Precancerous lesions are the most commonly cited factor in gastric cancer etiology. The sequence of events in intestinal-type gastric carcinogenesis is considered to be chronic gastritis, atrophy, intestinal metaplasia (IM), dysplasia, and carcinoma, respectively. Early diagnosis and treatment of advanced precursor lesions and gastric cancer is possible by identifying and monitoring patients with such premalignant lesions. In our study, we aimed to evaluate the long-term follow-up results of intestinal metaplasia in our hospital and the rate of progression to malignancy by comparing these patients with patients who have undergone gastroscopy without a diagnosis of intestinal metaplasia. One hundred and fifty-six followed-up patients out of 700 between the ages of 18 and 85 who were admitted to our hospital between 2009 and 2019, who were diagnosed with IM by pathological examination from biopsy material, and 150 patients who were not diagnosed with IM between 2009 and 2011 were included. The results of the cases were evaluated first retrospectively; then, the patients who were invited for control and underwent endoscopy were evaluated prospectively. IM and control groups were compared in terms of dysplasia and gastric cancer development. In addition, the IM group was compared in terms of 5 and 10 years of follow-up, extensive or local involvement, and complete and incomplete involvement in terms of dysplasia and cancer development. The follow-up period of the patients ranged from 1 to 10 years, and the mean follow-up interval was 4.2 ± 2.8 (min: 1; max: 10) years. Age, gender, and pathology results of the patients were examined in terms of IM type, localization of IM, pathology accompanying IM, and presence of Helicobacter pylori (Hp) infection and compared with the control group. While gastric carcinoma was detected in three of 156 patients in the IM group, gastric carcinoma was not detected in the follow-up of 150 patients in the control group. IM was most common in the antrum. Incomplete IM was detected in 89 patients, and complete IM in 69 patients. While two of the three patients with gastric carcinoma were localized to the antrum, one patient had incomplete-type IM and two patients had complete-type IM, and Hp was positive in two patients. While dysplasia was detected in nine of the patients diagnosed with IM, it was detected in two patients in the control group. A statistically significant difference was found between the IM and control groups in terms of dysplasia positivity (p = 0.037). On the other hand, no statistically significant difference was found between the IM and control groups in terms of age-group, gender, follow-up time group, and Hp positivity (p > 0.05). There was no significant difference between those who were followed up for 5 and 10 years in the IM group in terms of dysplasia and cancer development. Therefore, it is considered that patients with intestinal metaplasia may be followed up at longer intervals, except for patients with race, ethnicity, incomplete type, extensive involvement, and a family history of gastric cancer.

Gender differences in the relationship between alcohol consumption and gastric cancer risk are uncertain and not well-delineated.

The role of alcoholic and other beverage consumption in the etiology of gastric cancer is unknown. Several studies have summarized and established a significant association between heavy alcohol consumption and gastric cancer risk, but evidence on alcohol-related cancer risk is conflicting.

Microbiota dysbiosis in pancreatic cancer: evidence ofassociation and tumorigenesis

<p indent="0mm">Pancreatic cancer is a highly malignant disease with poor diagnosis and treatment. Its morbidity and mortality have recently significantly increased with a low survival rate. The 5-year overall survival rate is less than 1%, and the prognosis is extremely poor. Due to the difficulties and a low rate of early diagnosis, the prognosis of patients with pancreatic cancer after surgery will be greatly improved if early clinical diagnosis of pancreatic cancer is accomplished. There are many common risk factors for pancreatic cancer, such as chronic pancreatitis, diabetes, high-fat diets, obesity, and intestinal disorders. In the 1990s, when the etiology of gastric cancer was studied, <italic>Helicobacter pylori</italic> was found to be the causative factor of gastric cancer, and the correlation between microbiota and tumor pathogenesis provided a new clue for the study of tumor pathogenesis. Several lines of evidence have shown that pancreatic cancer is highly associated with changes in the human microbiota. Thus, in this paper, we review current evidence on the role of human microbiota in pancreatic cancer development and provide a perspective on the application of microbiota modulation in the early diagnosis and effective treatment of pancreatic cancer.