Risk Of Gastric Cancer Research Articles

Abstract C158: Contribution of multi-organ cancer predisposition genes for gastric cancer risk of different histological subtypes

Abstract Approximately 10% of gastric cancer (GC) cases exhibit familial clustering, yet only 1-3% can be explained by known hereditary syndromes, being Hereditary Diffuse Gastric Cancer (HDGC) the most well-established disease predisposing for diffuse gastric cancer. Familial intestinal gastric cancer (FIGC) has been defined clinically, but it remains mostly genetically unexplained. Likewise, the heritability of mixed GC remains to be uncovered. We aimed to estimate the frequency of known cancer predisposition gene variants in GC cases with family history of cancer and/or early onset. We evaluated the contribution of pathogenic and likely pathogenic (P/LP) variants in well-established and multi-organ cancer predisposition genes for GC risk in a large multi-center study involving 750 GC patients, either by targeted sequencing or whole exome sequencing. We identified 45 patients (6%) with P/LP variants in ATM (17 cases), BRCA2 (10 cases), MLH1 (five cases), TP53 (three cases), BRCA1, PALB2, RAD51D and CHEK2 (two patients each), and RAD51C and PMS2 (one case each), all mutually exclusive. The P/LP variant prevalence was higher in intestinal (9.8%) than in diffuse (4.3%) or mixed GC (4.5%) (p-value=0.023), with no clear difference per mutated gene by histological subtypes. Only sixteen of the 45 variant carriers fulfilled the criteria for genetic testing of at least one cancer predisposition syndrome. Our findings indicate that multi- organ cancer predisposition genes should be included in gene panels used for investigating germline variants in GC patients, especially when there is family history of cancer but irrespective of histology subtype, as this would increase the chance of identifying patients that might benefit from prevention and targeted treatment strategies. Citation Format: Ana P. Estrada-Florez, Paul C. Lott, Luis G. Carvajal Carmona. Contribution of multi-organ cancer predisposition genes for gastric cancer risk of different histological subtypes [abstract]. In: Proceedings of the 17th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2024 Sep 21-24; Los Angeles, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2024;33(9 Suppl):Abstract nr C158.

Risk Factors and Prevention of Stomach Cancer, Excluding Helicobacter pylori

Gastric cancer is a significant health problem owing to its high incidence and mortality rate. The risk factors for gastric cancer include both uncontrollable (e.g., age, sex, and genetic predisposition) and controllable factors (e.g., <i>Helicobacter pylori</i> infection, smoking, alcohol consumption, obesity, and high-salt diets). Although treatment of <i>H. pylori</i> infections has been implemented as a primary preventive measure, the risk of gastric cancer may persist, highlighting the need for additional preventive measures. This review discusses various risks and protective factors associated with gastric cancer, studies conducted on these factors, and chemoprevention. Smoking is a risk factor for this disease; thus, is not recommended and current smokers are encouraged to quit because cessation can reduce the risk of gastric cancer. Excessive alcohol intake has been reported to increase the risk of gastric cancer as has the consumption of high-salt foods that can damage the gastric mucosa. Additionally, increasing the intake of fruits and vegetables, known for their protective effects against gastric cancer, can aid in its prevention. Studies on chemopreventive agents, including nonsteroidal anti-inflammatory drugs (e.g., aspirin), statins, and metformin, have been reported; however, evidence of their effectiveness remains insufficient to recommend these agents as preventive treatments. Additional well-planned studies on preventive medications and dietary approaches are necessary.

Optimal Surveillance of Metachronous Gastric Lesion after Endoscopic Resection of Early Gastric Cancer.

Endoscopic resection (ER)-a minimal invasive procedure, compared to surgical gastrectomy, with the advantage of preserving the entire stomach and maintaining the patient's quality of life-is a widely used curative treatment for early gastric cancers (EGCs). Despite its advantages, such as the preservation of the whole stomach, a large area of the gastric mucosa with histologic changes such as atrophy and intestinal metaplasia remains after ER, and so does the risk of metachronous gastric cancers (MGCs). Therefore, regular surveillance endoscopy after curative ER of EGCs is important so that MGCs are detected early and so minimally invasive ER remains a treatment option. To date, the optimal interval for surveillance endoscopy after curative ER of EGCs has not been established. Therefore, this review summarizes the results of the published studies on this topic with the aim of establishing the optimal surveillance interval for early identification of MGCs. Based on my review, the median timing of MGC occurrence is within 3 years, and reports suggest biannual endoscopy during the first 3 years; however, the evidence suggests that individual patient characteristics may influence the risk of MGCs. Therefore, stratified endoscopic strategies for surveillance based on patient characteristics, such as age, family history of gastric cancer, synchronous gastric lesions, and corpus intestinal metaplasia, should be applied.

Clinical characteristics of patients with early gastric prematurity cancer and analysis of complications by endoscopic resection.

Gastric cancer, a prevalent malignancy, poses a severe threat to the health of residents in China. Timely intervention in early stages can extend patients' survival. To analyze clinical characteristics of patients with early gastric cancer and efficacy and risk of complications associated with endoscopic resection. This study included 175 patients with early gastric cancer treated at our hospital, with no restrictions on sex or age. General data, pathological information, and endoscopic biopsy results were obtained. The clinical characteristics of early gastric cancer were analyzed, and endoscopic resection was performed. Postoperative efficacy and incidence of complications were monitored. Statistical analysis was performed using SPSS 26.0 and GraphPad Prism 8.0 software. A total of 175 patients with early gastric cancer were included, with 75.43% (n = 132) males and 24.57% (n = 43) females. 38.29% (n = 67) and 35.43% (n = 62) of patients had a history of smoking and alcohol consumption, respectively. Comorbidities included diabetes (8.57%, n = 15), coronary heart disease (10.29%, n = 18), and hypertension (43.43%, n = 76), which was highly prevalent. A history of abdominal surgery and family history of digestive system cancer accounted for 21.14% and 17.14%, respectively. The most common lesion location was the antral part of the stomach (52.00%, n = 91), followed by the gastric angle, body, and fundus. The pathological types were predominantly high-grade intraepithelial neoplasia (28.00%, n = 49) and well-differentiated adenocarcinoma (26.86%, n = 47), followed by moderately differentiated adenocarcinoma, high-moderately differentiated adenocarcinoma, and moderate-lowly differentiated adenocarcinoma. 89.14% of the patients had intestinal metaplasia and 85.14% had atrophy. After endoscopic resection, re-examination revealed that 13 patients had cancer cells at the tissue margin, with a positive margin rate of 7.43%. Postoperative complications included no cases of gastrointestinal obstruction, but incisional infection (2.86%, n = 5), gastric perforation (1.14%, n = 2), and gastric bleeding (4%, n = 7) were present, with an overall incidence of 8.00%. Analysis of the clinical characteristics indicated that early gastric cancer is more prevalent in males with a history of hypertension, with lesions most commonly occurring in the antral region of the stomach. The pathological types are often high-grade intraepithelial neoplasia and well-differentiated adenocarcinoma, with over 85% of patients having comorbid intestinal metaplasia and atrophy. Despite endoscopic resection, a positive margin rate persisted, indicating a probability of residual cancer at the margins. Postoperative complications, such as gastrointestinal obstruction, incisional infection, gastric perforation, and gastric bleeding can occur and require timely symptomatic treatment.

Chronic Atrophic Gastritis and Intestinal Metaplasia: A Latin American Perspective

Gastric cancer (GC), a significant cause of mortality globally, is the leading cause of cancer-related deaths among Latin American men. GC is usually diagnosed at an advanced stage; therefore, therapeutic options are limited, and prognosis is poor. <i>Helicobacter pylori</i> infection remains the primary risk factor for GC; therefore, primary prevention directed toward diagnosis and treatment (“test-and-treat” strategy) is important. Western medicine guidelines recommend esophagogastroduodenoscopy (EGD) for at-risk individuals aged >40 years with regular surveillance in patients with gastric premalignant conditions (GPMC). However, limited availability of EGD in Latin America necessitates development of risk stratification tools to minimize the endoscopic burden. Results from the Chilean “Endoscopic Cohort and Histological Operative Link on Gastric Assessment (OLGA) Staging” (ECHOS study), propose endoscopic surveillance of advanced GPMC (OLGA/Operative Link for Gastric Intestinal Metaplasia [OLGIM] stages III–IV) with reliable risk stratification to facilitate early GC detection. Ensuring high-quality EGD and enhanced diagnostic yield of GPMC is essential. GPMC grading tools, such as the Kimura-Takemoto or Endoscopic Grading of Gastric Intestinal Metaplasia classification, should be incorporated into the regular risk assessment protocol. However, obtaining mapping gastric biopsies using standardized methods such as the updated Sydney System biopsy protocol, followed by grading of chronic atrophic gastritis with or without intestinal metaplasia using the OLGA and OLGIM staging systems are preferred for GC risk stratification. Recent GC prevention strategies recommended in Chile include a “test-and-treat” approach for <i>H. pylori</i> in individuals aged 35–44 years and combined <i>H. pylori</i>/pepsinogen I–II serology and EGD evaluation in patients aged >45 years to optimize the limited preventive resources available in the region.

Relationship between obesity severity and Helicobacter pylori eradication in patients undergoing bariatric and metabolic surgery: A post hoc analysis.

The global prevalence of obesity is increasing and represents a major public health challenge. However, there is a paucity of data regarding Helicobacter pylori (H pylori) eradication in people with obesity. The aim of the study is to examine the influence of obesity degree on H. pylori eradication in patients undergoing bariatric and metabolic surgery. A post hoc analysis was conducted in a cohort of 204 adults patients (129 individuals diagnosed with obesity, 75 normal weight) H. pylori positive, included in two multicenter, prospective studies. Patients underwent a 14-day quadruple concomitant treatment, and H. pylori eradication was assessed using the 13C-urea breath test. The cohort was stratified according to body mass index (BMI), and statistical analyses were performed using chi-squared test, Kruskal-Wallis test, and logistic regression. Eradication rates were significantly lower in patients with obesity compared with normal weight individuals (68.2% vs. 88.0%, OR 0.29, 95% CI 0.13-0.63, p < 0.01). Furthermore, within the population diagnosed with obesity, the degree of obesity correlated with decreased eradication rates, with class 3 (BMI 40.0-49.9) and class 4 (BMI ≥ 50.0) obesity showing the lowest rates (67% and 51%, with an OR 0.28 and 0.15 respectively, p < 0.01). Our results indicate that obesity may influence H. pylori eradication, especially among severe obesity patients undergoing bariatric surgery, which could have implications for the development of ulcers and gastritis as well as the risk of gastric cancer. Tailored eradication strategies may be necessary to improve treatment efficacy in this population.

A Systematic Review of Surgical and Pathological Outcomes in Patients With a CDH1 Mutation Undergoing Total Gastrectomy.

CDH1 (E-cadherin) genetic mutations are associated with a 30%-70% increased lifetime risk of hereditary diffuse gastric cancer (HDGC). Although prophylactic total gastrectomy (PTG) reduces long-term risk of gastric cancer, the associated morbidity and mortality remain unclear. This systematic review aims to characterise postoperative surgical outcomes in patients undergoing total gastrectomy. A systematic literature search was performed for studies reporting endoscopic surveillance, surgical and pathological outcomes for patients with CDH1 mutation undergoing a total gastrectomy. Thirty-nine studies included 1849 patients, of which 96% had a CDH1 (n = 1777) or CTNNA1 (n = 3) mutation. Endoscopy outcomes were reported for 1640 patients. Cancer foci were identified in 32% (n = 523/1640) and 71% of these patients went on to have a total gastrectomy (n = 369/523). The remaining 78% of patients did not have cancer foci detected on endoscopy (n = 1117/1640). Of these patients, 62% underwent a total gastrectomy (n = 688/1117) and 81% were found to have cancer on surgical histology (n = 556/688). Pathological staging was reported for 790 patients undergoing surgery, of which 68% had pT1 disease (n = 537). Postoperative complications were reported for 430 patients across 23 studies, with the most common complications being anastomotic strictures (25%), anastomotic leaks (13%), wound infections (12%) and pulmonary complications (11%). Only one postoperative death was reported within 30 days. Rates of early cancers are high in CDH1 patients undergoing PTG, highlighting the need for improvement in reliable endoscopic surveillance. Although postoperative mortality in this surgical cohort remains low, high rates of postoperative complications warrant careful patient counselling.

Trends of older gastric cancer incidence, mortality, and survival in the highest gastric cancer risk area in China: 2010–2019 and prediction to 2024

BackgroundGastric cancer is a major health problem worldwide, with a high incidence among older adults. Given the aging overall population, it was crucial to understand the current burden and prospective trend of older gastric cancer. This study aimed to analyze the temporal trends of the incidence, mortality, and survival of older gastric cancer in the highest gastric cancer risk area in China from 2010 to 2019, and to predict the future burden of older gastric cancer up to 2024.MethodsThe study was conducted in Gansu province, an area characterized by the highest gastric cancer incidence and mortality in China. The registration data of gastric cancer incidence and mortality from 2010 to 2019 were pooled from registries in the Gansu Cancer Registration System, while survival data were collected from the First Hospital of Lanzhou University, Lanzhou University Second Hospital, and Gansu Cancer Hospital. Chinese standard population in 2000 and the Segi’s world standard population were applied to calculate the age-standardized rate. Joinpoint regression was used to analyze the average annual percentage change (AAPC) in cancer incidence and mortality. Autoregressive Integrated Moving Average (ARIMA) models were employed to generate forecasts for incidence and mortality from 2020 to 2024.ResultsBased on registry data from 2010 to 2019, the incidence and mortality rates of gastric cancer among older adults remained stable. The incidence rates declined from 439.65 per 100,000 in 2010 to 330.40 per 100,000 in 2019, with an AAPC of -2.59% (95% confidence interval[CI], -5.14 to 0.04, P = 0.06). Similarly, the mortality rate changed from 366.98 per 100,000 in 2010 to 262.03 per 100,000 in 2019, with an AAPC of -2.55% (95% CI, -8.77–4.08%, P = 0.44). In the hospital-based cohort, the decline in survival rates was reported among older patients with gastric cancer in the highest gastric cancer risk area in China, with the 3-year overall survival (OS) decreasing from 58.5% (95% CI, 53.5–63.2%) in 2010 to 34.4% (95%CI, 32.1–36.7%) in 2019, and the 3-year progression-free survival (PFS) decreasing from 51.3% (95%CI, 47.5–55.1%) in 2010 to 34.2% (95%CI, 32.0–36.3%) in 2019, respectively. Moreover, forecasts generated by ARIMA models revealed a significant decline in the incidence and mortality of older gastric cancer in China from 2020 to 2024. Specifically, the incidence rate of older gastric cancer was expected to decrease from 317.94 per 100,000 population in 2020 to 205.59 per 100,000 population in 2024, while the anticipated mortality rate was estimated to decrease from 222.52 per 100,000 population in 2020 to 186.22 per 100,000 population in 2024.ConclusionFrom 2010 to 2019, the incidence and mortality of older gastric cancer remained stable in the highest gastric cancer risk area in China, while the survival rates showed a decline. Based on the ARIMA models, it was anticipated that there might be a continued decline in older gastric cancer incidence and mortality in the highest-risk area in China over the next five years.

Can patients with mild non-neoplastic lesions diagnosed at baseline screening be safely exempt from surveillance: evidence from multicenter community-based cohorts.

Surveillance recommendations for gastric cancer (GC) in current guidelines focused on advanced precancerous lesions and were based on precise diagnosis of severity/extent of baseline lesions. We aimed to develop a less endoscopy-related equipment-dependent risk-stratification tool, and assessed whether mild-precursor-lesion patients can be safely exempt from surveillance. In the multicenter community-based cohort, 75,051 participants receiving baseline endoscopy were enrolled during 2015-2017 and followed-up until 2021. Cumulative incidence rates (CIRs) of GC for precancerous-conditions were calculated by Kaplan-Meier method and compared by Log-rank tests. Mixed-effects Cox regression models were used to detect potential factors for progression towards GC. A risk score was calculated as counts of selected factors. An independent cohort, including 26,586 participants was used for external validation. During a median follow-up of 6.25 years, CIRs of GC were 0.302%, 0.436%, and 4.756% for normal group, non-neoplastic (atrophic gastritis/intestinal metaplasia) and neoplastic lesions (low-grade/high-grade dysplasia), respectively (Ptrend<0.001). Four predictors, including male, ⩾60 years, smoking, and limited vegetable consumption, were selected for risk-stratification. High-risk patients (⩾3 risk factors) with non-neoplastic lesions showed higher GC risks (adjusted HR=7.73, 95%CI: 4.29-13.92), and their four-year CIR reached the one-year CIR of neoplastic lesions. Further categorizing non-neoplastic lesions by histological grade, both patients with moderate-to-severe lesions (aHR=3.07, 95%CI: 1.67-5.64) and high-risk patients with mild lesions (aHR=7.29, 95%CI: 3.58-14.86) showed higher risks. Consistent trends were observed in validation cohort. High-risk mild-precursor-lesion patients should receive surveillance within 3-5 years after baseline screening. Our study provides evidence on supplementing current guideline recommendations.

Risk of Gastric and Small Intestinal Cancer in Patients With Lynch Syndrome: Data From a Large, Community-Based US Population.

Risk of gastric and small intestinal cancer in Lynch syndrome (LS) remains poorly understood. We investigated the risk of gastric and small intestinal cancer in patients with LS in a large, community-based population. This retrospective cohort study included all patients diagnosed with LS between January 1, 1997, and December 31, 2020, at Kaiser Permanente Northern California. Cumulative incidence of gastric cancer and small intestinal cancer was calculated using competing risk methodology. Among 1,106 patients with LS with a median follow-up of 19.3 years (interquartile range [IQR] 9.4-24.0 years), 11 developed gastric cancer (8 MSH2 , 2 MLH1 and 1 PMS2 ) with a median diagnosis age of 56 years (IQR 42-63 years) and 11 developed small intestinal cancer (6 MSH2 , 3 MLH1 , 1 MSH6 and 1 PMS2 ) with a median diagnosis age of 57 years (IQR 50-66 years). Cumulative incidence by age 80 years was 7.26% (95% confidence internal [CI], 1.80-18.03%) for men and 3.43% (95% CI, 0.50-11.71%) for women for gastric cancer and 7.28% (95% CI, 3.19-13.63%) for men and 2.21% (95% CI, 0.23-9.19%) for women for small intestinal cancer. Pathogenic variant carriers of MSH2 and MLH1 had the highest risk of gastric and small intestinal cancer. History of Helicobacter pylori infection was associated with increased risk of gastric cancer (adjusted odds ratio 5.52; 95% CI, 1.72-17.75). Patients with LS, particularly MSH2 and MLH1 pathogenic variant carriers, had significantly increased lifetime risk of gastric and small intestinal cancer. Testing and treatment of H. pylori infection should be considered for all patients with LS.

Acarbose might be associated with reduced risk of gastric cancer in patients with diabetes mellitus: A nationwide population-based cohort study.

Several epidemiologic studies have revealed a higher risk of cancer in patients with diabetes mellitus (DM) relative to the general population. To investigate whether the use of acarbose was associated with higher/lower risk of new-onset cancers. We conducted a retrospective cohort study, using a population-based National Health Insurance Research Database of Taiwan. Both inpatients and outpatients with newly onset DM diagnosed between 2000 and 2012 were collected. The Adapted Diabetes Complications Severity Index (aDCSI) was used to adjust the severity of DM. The Cox proportional hazards regression model was used to estimate the hazard ratio (HR) of disease. A total of 22 502 patients with newly diagnosed DM were enrolled. The Cox proportional hazards regression model indicating acarbose was neutral for risk for gastroenterological malignancies, when compared to the acarbose non-acarbose users group. However, when gastric cancer was focused, acarbose-user group had significantly lowered HR than non-acarbose users group (p = 0.003). After adjusted for age, sex, cancer-related comorbidity, severity of DM, and co-administered drugs, the HR of gastric cancer risk was 0.43 (95% CI = 0.25-0.74) for acarbose-user patients. This long-term population-based study demonstrated that acarbose might be associated with lowered risk of new-onset gastric cancer in diabetic patients after adjusting the severity of DM.

Gastric Cancer Screening: Intention to Adhere and Patients' Perspective.

Gastric cancer (GC) is the third cause of cancer mortality worldwide. A screening strategy that combines an upper gastrointestinal endoscopy (UGIE) with a screening colonoscopy may be cost-effective in intermediate-risk regions. This study aimed to evaluate the intention to adhere to combined endoscopic screening and assess knowledge of GC symptoms, risk factors, and barriers to screening. Cross-sectional study enrolling individuals eligible for CRC screening in northern Portugal, where a populational fecal occult blood test (FOBT) program is implemented. The validated PERCEPT-PREVENT tool was applied across three groups: (a) not yet invited to CRC screening, (b) FOBT-positive referred to colonoscopy, and (c) primary colonoscopy screening. A high acceptance rate was observed for combined endoscopic screening (94%; n = 264) [not yet invited to CRC screening 98% (n = 90) vs. FOBT-positive referred to colonoscopy 90% (n = 103) vs. primary colonoscopy 97% (n = 71); p = 0.017], with the vast majority reporting intention to adhere in the setting of full reimbursement (97%; n = 255). Most respondents were unaware of any possible GC symptom (76%; n = 213), risk factor (73%; n = 205), and UGIE-related complication (85%; n = 237). Regular follow-up with the primary care physician (Odds Ratio (OR) 27.59, 95% confidence interval (CI) 2.99-254.57), lower perceived negative health consequences of UGIE (OR 1.40, 95% CI 1.13-1.74), and lower perceived financial burden (OR 2.46, 95% CI 1.04-5.85) were the only factors independently associated with a higher intention to undergo combined screening. Willingness to undergo combined endoscopic screening was notably high and positively impacted by lower perceived barriers. Additional efforts should be undertaken to improve levels of digestive health literacy.

787. THE CHALLENGE OF GASTRO-ESOPHAGEAL ONCOLOGICAL SURGERY AFTER BARIATRIC PROCEDURES: EXPERIENCE OF A REFERRAL HIGH-VOLUME UPPER GI SURGICAL CENTER

Abstract Background The effectiveness of bariatric surgery for weight loss in morbidly obese patients has been well established and it's becoming more common as many surgeons are trained to perform them safely, even in older patients. Obesity is associated with reflux and hormonal imbalances that increase the risk of Barrett's esophagus, esophageal adenocarcinoma and gastric cancer. Bariatric procedures alter gastric anatomy, vascularization and lymphatic drainage and render subsequent upper gastrointestinal surgery for malignancies a technical challenge, that will present more and more in the future. We present laparoscopic sleeve gastrectomy, gastric bypass and gastric banding conversion to oncological respective surgeries. Methods We retrospectively reviewed the medical records of our referral high-volume center for upper gastrointestinal surgery and identified patients who underwent upper gastrointestinal oncologic surgery from January 1998 to May 2024. We selected all patients who had previously undergone bariatric surgery (laparoscopic sleeve gastrectomy, laparoscopic gastric bypass, gastric banding, or other less common procedures). Three patients met our criteria, and we recorded: demographic characteristics, surgical technique, oncologic surgical outcome, postoperative complications, long-term complications, and oncologic follow-up. Results A hybrid IvorLewis esophagectomy was performed years after a sleeve gastrectomy for distal esophageal adenocarcinoma. The sleeve was used for gastric pull-up, adequately vascularized by the right gastroepiploic artery as demonstrated by intraoperative indocyanine green. A patient developed adenocarcinoma of the cardia after Roux-en-Y gastric bypass, infiltrating the gastric pouch, the gastric remnant and liver S2. After neoadjuvant chemotherapy, an open Ivor-Lewis esophagectomy was performed using the gastric remnant for a pull-up. In a third patient, a locally advanced adenocarcinoma of the stomach developed after gastric banding. After neoadjuvant chemotherapy, an open total gastrectomy with Roux-en-Y esophagojejunostomy was performed. Conclusion We report three cases of successful esophago-gastric oncological surgery in patients with altered anatomy and vascularization due to previous bariatric surgery, without major postoperative complications or mortality. Oncologic benchmarks for both esophageal and gastric surgery were met as a high lymph node yield and oncologic margins were maintained. Our heterogeneous series suggests that sleeve gastrectomy, gastric bypass, and gastric banding surgery can be successfully converted to resective surgeries after a metachronous neoplasia diagnosis in high-volume upper gastrointestinal centers. These and similar modified reconstructive techniques are likely to be used in the future as metabolic surgery and esophago-gastric cancer are increasing.

Endoscopic appearances of gastric mucosa in different endoscopic models according to H. pylori infection status.

H. pylori infection has been recognized as a type 1 carcinogen of the gastric malignancy; therefore, early diagnosis and treatment are the corner stone of eradication. Recent findings have also shown that atrophy and intestinal metaplasia remain after successful eradication, which moderately increases the risk of gastric cancer compared with those who have never infected, so the evaluation of gastric mucosa during gastroscopy is important. We aimed to describe and summarize the reliable literature and proposed features of H. pylori infection status and gastritis in research on newly developed endoscopic models that influence clinical practice. In the result, conventional white light endoscopic, image-enhanced endoscopic models, and studies related to the Kyoto classification of gastritis were searched and reviewed. Kyoto classification of gastritis and modified Kyoto classification scoring model for gastritis using conventional white light image (CWLI) endoscopy is an effective tool for evaluating current H. pylori infection status, past infections, eradications, noninfections, and pre-cancerous conditions. This model is widely used, low cost, and time-efficient, and is supported by recent findings. Advanced image-enhanced endoscopic models combined with magnifying endoscopy provide more clear endoscopic features for H. pylori infection status and early gastric cancer. According to H pylori infection status, endoscopic prediction of gastric mucosal surface architecture analysis is possible, which influences clinical management. Endoscopic models might lead us to accurate and early diagnose of H. pylori infection status and may not be effective only for the eradication of H. pylori infection but also in the detection of early gastric cancer status.

Common variants of vitamin D receptor gene polymorphisms and risk of gastric cancer: A meta-analysis.

While earlier studies have suggested that variations in the vitamin D receptor (VDR) gene could influence the susceptibility to gastric cancer (GC), the results have shown inconsistency. This meta-analysis aimed to examine the association of 5 common polymorphisms in VDR, including Taq1 rs731236 (T > C), FokI rs2228570 (C > T), Cdx2 rs11568820 (G > A), BsmI rs1544410 (G > A), and ApaI rs7975232 (G > T) with the risk of GC. A comprehensive search was carried out in PubMed, Web of Science, and Scopus to identify relevant studies published until January 2024. Odds ratios (ORs) with 95% confidence intervals (CIs) were utilized to assess the magnitude of associations. Nine studies, with 2837 participants (1215 GC cases and 1622 healthy controls), were eligible. The FokI rs2228570 polymorphism showed a significant correlation with heightened susceptibility to GC under the recessive model (OR = 1.52; 95% CI: 1.06-2.19) and homozygote comparison (TT vs CC; OR = 1.59; 95% CI: 1.09-2.31). Taq1 rs731236 was also linked to an elevated risk of GC under the same models (recessive OR = 1.65; 95% CI: 1.14-2.39; homozygote OR = 1.68; 95% CI: 1.11-2.54). In the sensitivity analysis, when studies not adhering to Hardy-Weinberg equilibrium were excluded, the relationship between FokI rs2228570 polymorphism and GC disappeared, while the association for Taq1 rs731236 remained consistent. No significant association was identified for BsmI rs1544410, ApaI rs7975232, and Cdx2 rs11568820. This study revealed that FokI rs2228570 and Taq1 rs731236 polymorphisms of VDR might be linked to the odds of GC.

Autoimmune gastritis studies and gastric cancer: True renaissance or bibliometric illusion.

A bibliometric analysis of studies dedicated to autoimmune gastritis (AIG) recently published demonstrated a noteworthy surge in publications over the last three years. This can be explained by numerous publications from different regions of the world reporting the results of several studies that stimulated reassessment of our view of AIG as a precancerous condition. Follow-up studies and retrospective analyses showed that the risk of gastric cancer (GC) in AIG patients is much lower than expected if the patients ever being infected with Helicobacter pylori (H. pylori) were excluded. The low prevalence of precancerous lesions, such as the incomplete type of intestinal metaplasia, may explain the low risk of GC in AIG patients because the spasmolytic polypeptide-expressing metaplasia commonly observed in AIG does not involve clonal reprogramming of the gastric gland and can be considered as an adaptive change rather than a true precancerous lesion. However, changes in gastric secretion due to the progression of gastric atrophy during the course of AIG cause changes in the gastric mic-robiome, stimulating the growth of bacterial species such as streptococci, which may promote the development of precancerous lesions and GC. Thus, Streptococcus anginosus exhibited a robust proinflammatory response and induced the gastritis-atrophy-metaplasia-dysplasia sequence in mice, reproducing the well-established process for carcinogenesis associated with H. pylori. Prospective studies in H. pylori-naïve patients evaluating gastric microbiome changes during the long-term course of AIG might provide an explanation for the enigmatic increase in GC incidence in the last decades in younger cohorts, which has been reported in economically developed countries.

Helicobacter pylori infection facilitates cell migration and potentially impact clinical outcomes in gastric cancer

Gastric cancer is a significant health concern worldwide. Helicobacter pylori (HP) infection is associated with gastric cancer risk, but differences between HP-infected and HP-free gastric cancer have not been studied sufficiently. The objective of this study was to investigate the effects of HP infection on the viability and migration of gastric cancer cells and identify potential underlying genetic mechanisms as well as their clinical relevance. Cell counting kit-8, lactate dehydrogenase, wound healing, and transwell assay were applied in the infection model of multiple clones of HP and multiple gastric cancer cell lines. Genes related to HP infection were identified using bioinformatics analysis and subsequently validated using real-time quantitative PCR. The association of these genes with immunity and drug sensitivity of gastric cancer was analyzed. Results showed that HP has no significant impact on viability but increases the migration of gastric cancer cells. We identified 1405 HP-upregulated genes, with their enriched terms relating to cell migration, drug, and immunity. Among these genes, the 82 genes associated with survival showed a significant impact on gastric cancer in consensus clustering and LASSO prognostic model. The top 10 hub HP-associated genes were further identified, and 7 of them were validated in HP-infected cells using real-time quantitative PCR, including ERBB4, DNER, BRINP2, KCTD16, MAPK4, THPO, and VSTM2L. The overexpression experiment showed that KCTD16 medicated the effect of HP on gastric cancer migration. Our findings suggest that HP infection may enhance the migratory potential of gastric cancer cells and these genes might be associated with immunity and drug sensitivity of gastric cancer. In human subjects with gastric cancer, HP presence in tumors may affect migration, immunity, and drug sensitivity.

Thirdhand smoke exposure promotes gastric tumor development in mouse and human

The pollution of indoor environments and the consequent health risks associated with thirdhand smoke (THS) are increasingly recognized in recent years. However, the carcinogenic potential of THS and its underlying mechanisms have yet to be thoroughly explored. In this study, we examined the effects of short-term THS exposure on the development of gastric cancer (GC) in vitro and in vivo. In a mouse model of spontaneous GC, CC036, we observed a significant increase in gastric tumor incidence and a decrease in tumor-free survival upon THS exposure as compared to control. RNA sequencing of primary gastric epithelial cells derived from CC036 mice showed that THS exposure increased expression of genes related to the extracellular matrix and cytoskeletal protein structure. We then identified a THS exposure-induced 91-gene expression signature in CC036 and a homologous 84-gene signature in human GC patients that predicted the prognosis, with secreted phosphoprotein 1 (SPP1) and tribbles pseudokinase 3 (TRIB3) emerging as potential targets through which THS may promote gastric carcinogenesis. We also treated human GC cell lines in vitro with media containing various concentrations of THS, which, in some exposure dose range, significantly increased their proliferation, invasion, and migration. We showed that THS exposure could activate the epithelial-mesenchymal transition (EMT) pathway at the transcript and protein level. We conclude that short-term exposure to THS is associated with an increased risk of GC and that activation of the EMT program could be one potential mechanism. Increased understanding of the cancer risk associated with THS exposure will help identify new preventive and therapeutic strategies for tobacco-related disease as well as provide scientific evidence and rationale for policy decisions related to THS pollution control to protect vulnerable subpopulations such as children.

Association between prediabetes and the incidence of gastric cancer: A meta-analysis.

Prediabetes has been found to be associated with an elevated overall risk of cancer, which may be site-specific. we performed a protocol for systematic review and meta-analysis to investigate the correlation between prediabetes and the incidence of gastric cancer (GC). A thorough review of the literature was conducted in the PubMed, Embase, and Web of Science databases to identify pertinent observational studies with longitudinal follow-up. The random-effects model was employed to consolidate the data, taking into account the potential impact of heterogeneity. A total of 13 datasets from 8 prospective cohort studies were included. The prevalence of prediabetes was 9.6%. During the mean follow-up duration of 7.1 to 12.2 years, 33,135 patients were diagnosed with GC. According to the results of the pooled analysis, prediabetes was associated with a mildly higher incidence of GC over time (risk ratio: 1.07, 95% confidence interval: 1.01-1.13, P = .03; I2 = 44%). Subsequent subgroup analyses indicated that the relationship between prediabetes and the heightened risk of GC may not be substantially influenced by factors such as the country in which the study was conducted, the average age of participants, their gender, the definition of prediabetes used, the prevalence of prediabetes at the beginning of the study, the incidence of GC within the studied population, or the adjustment made for body mass index (P for subgroup difference all >.05). The presence of prediabetes may increase the risk of GC by a mild amount when compared with people with normoglycemia in community-derived adult populations.

Does ambient particulate matter 1 increase the risk of gastric cancer in the northwest of China?

Gastric cancer (GC) remains a significant health concern in Gansu province, China, with morbidity and mortality rates surpassing national averages. Despite the recognized health risks associated with ambient particulate matter with an aerodynamic diameter <1 μm (PM1), the relationship between PM1 exposure and GC incidence has not been extensively studied. Data on GC cases from 2013 to 2021 were gathered from 262 hospitals in Gansu, China. Concurrently, data on the normalized vegetation index (NDVI), gross domestic product (GDP), drinking and smoking behavioral index (DSBI), PM1, PM2.5, and PM2.5-1 were collected. Utilizing a Bayesian conditional autoregressive (CAR) combined generalized linear model (GLM) with quasi-Poisson regression, we evaluated the impact of PM1, PM2.5, PM2.5-1, NDVI, DSBI, and GDP on GC morbidity while adjusting for potential confounders. Our analysis indicated that exposure to PM1 (μg/m3) is significantly positively correlated with GC incidence in regions with an overall age-standardized incidence rate (ASIR) >40 (relative risks [RR]: 1.023, 95% confidence intervals [CI, 1.007, 1.039]), male ASIR >50 (RR: 1.014, 95% CI [1.009, 1.019]), and female ASIR >20 (RR: 1.010, 95% CI [1.002, 1.018]). PM2.5, PM2.5-1, DSBI, and GDP were positively correlated with GC incidence, while NDVI was negatively correlated in the study regions. Our findings provided evidence of a positive correlation between PM1 exposure and GC incidence in high-risk areas of GC within arid regions. Further research is warranted to elucidate the complex nonlinear relationships between environmental factors and GC. These insights could inform strategies for improving the control and prevention of GC in Gansu and similar regions.