Global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035.

OBJECTIVE: To study the historical global incidence and mortality trends of gastric cancer and predicted mortality of gastric cancer by 2035. METHODS: Incidence data were retrieved from the Cancer Incidence in Five Continents (CI5) volumes I-XI, and mortality data were obtained from the latest update of the World Health Organization (WHO) mortality database. We used join-point regression analysis to examine historical incidence and mortality trends and used the package NORDPRED in R to predict the number of deaths and mortality rates by 2035 by country and sex. RESULTS: More than 1,089,000 new cases of gastric cancer and 769,000 related deaths were reported in 2020. The average annual percent change (AAPC) in the incidence of gastric cancer from 2003 to 2012 among the male population, South Korea, Japan, Malta, Canada, Cyprus, and Switzerland showed an increasing trend (P > 0.05); among the female population, Canada [AAPC, 1.2; (95%Cl, 0.5-2), P < 0.05] showed an increasing trend; and South Korea, Ecuador, Thailand, and Cyprus showed an increasing trend (P > 0.05). AAPC in the mortality of gastric cancer from 2006 to 2015 among the male population, Thailand [3.5 (95%cl, 1.6-5.4), P < 0.05] showed an increasing trend; Malta Island, New Zealand, Turkey, Switzerland, and Cyprus had an increasing trend (P > 0.05); among the male population aged 20-44, Thailand [AAPC, 3.4; (95%cl, 1.3-5.4), P < 0.05] showed an increasing trend; Norway, New Zealand, The Netherlands, Slovakia, France, Colombia, Lithuania, and the USA showed an increasing trend (P > 0.05). It is predicted that the mortality rate in Slovenia and France's female population will show an increasing trend by 2035. It is predicted that the absolute number of deaths in the Israeli male population and in Chile, France, and Canada female population will increase by 2035. CONCLUSION: In the past decade, the incidence and mortality of gastric cancer have shown a decreasing trend; however, there are still some countries showing an increasing trend, especially among populations younger than 45 years. Although mortality in most countries is predicted to decline by 2035, the absolute number of deaths due to gastric cancer may further increase due to population growth.

Association between serum total cholesterol and the development of gastric cancer: A two-way two-sample Mendelian randomization study.

Previous epidemiologic studies have suggested a potential negative correlation between total cholesterol (TC) and Gastric cancer (GC); however, several observational studies have shown conflicting results and have failed to provide definitive evidence for a causal relationship between TC and GC. Therefore, we conducted a 2-sample bidirectional Mendelian randomization (MR) study to explore the genetic correlation and potential causal relationship between the 2 variables. We screened for single nucleotide polymorphisms (SNPs) associated with TC and GC utilizing a large-scale genome-wide association study (GWAS) public database. The causal relationship was analyzed using 5 MR analysis methods: inverse variance weighting (IVW), weighted median, MR-Egger regression, weighted mode, and simple mode. Additionally, reverse MR analysis was performed to evaluate the possibility of reverse causality. Sensitivity analyses were conducted, including heterogeneity tests, horizontal multiple validity tests, and leave-one-out tests. After meticulous screening, 79 SNPs were identified as instrumental variables (IVs). The IVW method revealed a causal relationship between TC and GC (OR = 0.844; 95% CI: 0.741-0.961; P = .01). Sensitivity analyses did not detect significant horizontal pleiotropy. Though heterogeneity was observed in the forward MR analysis (IVW, Qp = 0.0006), the results remained reliable as we utilized the IVW random-effects model as the primary analytical method. Furthermore, inverse MR analysis found no evidence of reverse causality between TC and GC, effectively ruling out the influence of GC on the reverse causality of TC. Our MR study provided evidence of a causal association between TC and GC, suggesting that TC acts as a protective factor against GC due to its negative association with the disease.

Risk of map-like redness development after eradication therapy for Helicobacter pylori infection.

BACKGROUND: Map-like redness is a newly identified endoscopic risk factor for gastric cancer in patients who received Helicobacter pylori eradication therapy. However, the incidence rate of map-like redness in patients who received eradication, and the risk factors for the development of map-like redness remain unclear. We hence aimed to investigate the incidence rate of map-like redness at 1-year post H. pylori eradication, and evaluated its associations with map-like redness and gastric cancer in relation with gastric condition. MATERIALS AND METHODS: Endoscopic severity of gastritis and map-like redness were retrospectively evaluated according to the Kyoto Classification of Gastritis in patients who had undergone endoscopy before and after H. pylori eradication therapy. RESULTS: The incidence rate of map-like redness for all 328 patients at a mean of 1.2 ± 0.6 years after eradication was 25.3% (95% confidence interval [CI]: 20.7%-30.4%). Patients who developed map-like redness were older, had more severe atrophy and intestinal metaplasia, a higher total score of the Kyoto Classification of Gastritis both before and after eradication, and a higher rate of gastric cancer history than patients who did not have map-like redness. On multivariate analysis, risk of map-like redness was increased in patients with intestinal metaplasia (odds ratio [OR]: 2.794, 95% CI: 1.155-6.757) and taking acid inhibitors (OR: 1.948, 95% CI: 1.070-3.547). Characteristics of H. pylori-positive patients with gastric cancer history were patients who were older (OR: 1.033, 95% CI: 1.001-1.066), taking acid inhibitors (OR: 4.456, 95% CI: 2.340-8.484), and with occurrence of map-like redness after eradication therapy (OR: 2.432, 95% CI: 1.264-4.679). CONCLUSIONS: Map-like redness is observed in one fourth of patients at 1-year post eradication. Patients who developed map-like redness were found to have severe intestinal metaplasia and taking acid inhibitors, and hence such patients require increased attention at surveillance endoscopy.

Lifestyle Behaviors in Patients With Gastric Cancer: Continuous Need for Alcohol Abstinence and Muscle Strength Training Education.

PURPOSE: This study was performed to assess the lifestyle-related behaviors of patients with gastric cancer (GC) and to investigate the associations between the time since GC diagnosis and these behaviors. MATERIALS AND METHODS: This study included 29,478 adults (including 338 patients with GC) aged ≥ 40 years who participated in the Korea National Health and Nutrition Examination Survey 2014-2021. Multiple logistic regression analysis explored the associations between the time since GC diagnosis (patients diagnosed with GC less than 5 years ago [<5 years group] and those diagnosed with GC 5 or more than years ago [≥5 years group]) and lifestyle factors. Subgroup analyses were conducted based on age and sex. RESULTS: The current smoking rate was not lower in the GC group than in the healthy group, regardless of time since diagnosis. Compared to the healthy controls, monthly alcohol intake was lower in the <5 years group (odds ratio [OR], 0.450; 95% confidence interval [CI], 0.275-0.736). The ≥5 years group showed a lower rate of strength training (OR, 0.548; CI, 0.359-0.838), compared with the healthy control group. Subgroup analysis focusing on the ≥5 years group revealed a significantly lower rate of strength training, particularly in patients aged ≥65 years and male patients (OR, 0.519 and 0.553; CI, 0.302-0.890 and 0.340-0.901, respectively). CONCLUSIONS: Clinicians should continue educating patients on lifestyle behavior modifications, particularly alcohol abstinence, even beyond 5 years after GC diagnosis. Education on strength training is especially important for patients ≥65 years or male patients.

Proton pump inhibitors are not associated with fundic gland polyps - a systematic review that takes into consideration all known confounders.

Sporadic fundic gland polyps (FGPs) progress, albeit rarely, to dysplasia and cancer. Two meta-analyses, including 8 and 11 studies, concluded that proton pump inhibitors (PPIs) were associated with FGPs. Intervention is considered unnecessary when FGPs have a background of PPIs use. Both meta-analyses, however, disregarded known confounders: age, sex, endoscopy indications, study design (prospective or retrospective), duration of PPI use, and H. pylori infection. Confounders are known to invalidate meta-analyses. We followed PRIXMA guidelines and searched the literature for studies on FGPs in PPI-users and PPI-nonusers. In the 22 studies searched, we compared FGPs in PPI-users (n = 6534) and PPI-nonusers (n = 41 115). Heterogeneity was significant (Cochran Q = 277.8, P < 0.0001; I2 = 92.8%), annulling meta-analysis performed by blanket tallying. To offset the above confounders, we matched PPI-users and PPI-nonusers by (a) age and sex (n = 4300 and 29 307, respectively) and (b) their propensity scores derived from the confounders (n = 2950 and 4729, respectively). After both matching, FGPs were not significantly different between PPI-users and PPI-nonusers [odds ratio (OR) = 1.1, P = 0.3078; OR = 0.9, P = 0.3258, respectively]. Furthermore, FGP frequency did not correlate with increasing duration of PPI use (Pearson and Spearman correlation coefficients = 0.1162, 0.0386, P < 0.6064, 0.8646, respectively); it was not significantly different between any of the duration periods of observation, namely, <10, 10-20, 20-40, >40 months, nor was it significantly different between PPI-users and PPI-nonusers within each duration period (P > 0.05). We conclude that PPIs are not associated with FGPs, implying that a background history of PPI use is not a justification for nonintervention in the management of FGPs.

Causal link between hypothyroidism and gastric cancer risk: insights gained through multivariable Mendelian randomization and mediation analysis.

Background: Gastric cancer (GC) is the third leading cause of cancer death worldwide, and hypothyroidism has been identified as a potential influencing factor. Despite known associations between hypothyroidism and various cancers, the causal link between hypothyroidism and GC and potential mediators of this relationship remains unclear. This study aimed to clarify these relationships using Mendelian randomization (MR). Methods: Utilizing genetic variant information from the FinnGen and MRC Integrative Epidemiology Unit open genome-wide association studies (GWAS) databases, we conducted univariable and multivariable MR analyses to explore the causal relationship between hypothyroidism and GC risk. The analysis was adjusted for confounders such as BMI, smoking status, and alcohol intake, and included mediator MR analysis to examine the role of high cholesterol. Results: We identified a significant inverse association between hypothyroidism and GC risk (OR = 0.93, 95% CI= 0.89-0.98, P = 0.003), with no evidence of reverse causation or pleiotropy. Adjustments for Helicobacter pylori infection weakened this association. Mediator analysis highlighted high cholesterol levels, chronic hepatitis B infection, and diabetes/endocrine disease status as significant mediators of the protective effect of hypothyroidism on GC risk. Conclusion: Our findings suggest that hypothyroidism may confer a protective effect against GC, mediated in part by high cholesterol and other factors. These results underscore the importance of thyroid function and metabolic health in GC risk, offering new insights for preventive strategies and highlighting the need for further research into these complex associations.

Ultra-Processed Food Consumption and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.

Gastroenteropancreatic neuroendocrine neoplasms: current development, challenges, and clinical perspectives.

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients.

Helicobacter pylori Treatment and Gastric Cancer Risk Among Individuals With High Genetic Risk for Gastric Cancer.

Importance: Helicobacter pylori treatment and nutrition supplementation may protect against gastric cancer (GC), but whether the beneficial effects only apply to potential genetic subgroups and whether high genetic risk may be counteracted by these chemoprevention strategies remains unknown. Objective: To examine genetic variants associated with the progression of gastric lesions and GC risk and to assess the benefits of H pylori treatment and nutrition supplementation by levels of genetic risk. Design, Setting, and Participants: This cohort study used follow-up data of the Shandong Intervention Trial (SIT, 1989-2022) and China Kadoorie Biobank (CKB, 2004-2018) in China. Based on the SIT, a longitudinal genome-wide association study was conducted to identify genetic variants for gastric lesion progression. Significant variants were examined for incident GC in a randomly sampled set of CKB participants (set 1). Polygenic risk scores (PRSs) combining independent variants were assessed for GC risk in the remaining CKB participants (set 2) and in an independent case-control study in Linqu. Exposures: H pylori treatment and nutrition supplementation. Main Outcomes and Measures: Primary outcomes were the progression of gastric lesions (in SIT only) and the risk of GC. The associations of H pylori treatment and nutrition supplementation with GC were evaluated among SIT participants with different levels of genetic risk. Results: Our analyses included 2816 participants (mean [SD] age, 46.95 [9.12] years; 1429 [50.75%] women) in SIT and 100 228 participants (mean [SD] age, 53.69 [11.00] years; 57 357 [57.23%] women) in CKB, with 147 GC cases in SIT and 825 GC cases in CKB identified during follow-up. A PRS integrating 12 genomic loci associated with gastric lesion progression and incident GC risk was derived, which was associated with GC risk in CKB (highest vs lowest decile of PRS: hazard ratio [HR], 2.54; 95% CI, 1.80-3.57) and further validated in the analysis of 702 case participants and 692 control participants (mean [SD] age, 54.54 [7.66] years; 527 [37.80%] women; odds ratio, 1.83; 95% CI, 1.11-3.05). H pylori treatment was associated with reduced GC risk only for individuals with high genetic risk (top 25% of PRS: HR, 0.45; 95% CI, 0.25-0.82) but not for those with low genetic risk (HR, 0.81; 95% CI, 0.50-1.34; P for interaction = .03). Such effect modification was not found for vitamin (P for interaction = .93) or garlic (P for interaction = .41) supplementation. Conclusions and Relevance: The findings of this cohort study indicate that a high genetic risk of GC may be counteracted by H pylori treatment, suggesting primary prevention could be tailored to genetic risk for more effective prevention.

Clinicopathological Characteristics and Risk Factors of Young-Onset Gastric Carcinoma: A Systematic Review and Meta-analysis.

INTRODUCTION: The characteristics of gastric carcinoma in young individuals differ from that in older individuals. We conducted a systematic review and meta-analysis to explore the clinicopathological features and risk factors associated with young-onset (younger than 50 years) gastric carcinoma. METHODS: We searched for studies published between January 1, 1990, and September 1, 2023, on patients with young-onset gastric carcinoma in PubMed, EMBASE, Web of Science, and MEDLINE to explore clinicopathological characteristics among this specific patient group. Extracted information included the proportion of patients with symptoms or family history of gastric cancer, tumor location, and histological features such as Lauren or World Health Organization histological classification and degree of differentiation. Additional analyses were conducted on risk factors such as positive family history, Helicobacter pylori infection, or high-risk nutritional or behavioral factors. The estimates were derived using random or fixed-effect models and included subgroup analyses based on different sex and age groups. This study was registered in PROSPERO (CRD42023466131). RESULTS: We identified 5,696 records, 1,292 were included in the quality assessment stage. Finally, 84 studies from 18 countries or regions including 89,447 patients with young-onset gastric carcinoma were included. Young-onset gastric carcinoma has slight female predominance (53.7%, 95% confidence interval [CI]: 51.6-55.7%), with most having symptoms (87.0%, 95% CI: 82.4%-91.7%). Family history was reported in 12.1% (95% CI: 9.5%-14.7%). H. pylori infection was detected in 60.0% of cases (95% CI: 47.1%-72.8%). Most of these carcinomas were in the non-cardia region (89.6%, 95% CI: 82.4%-96.8%), exhibiting Lauren diffuse-type histology (71.1%, 95% CI: 66.8%-75.3%) and poor/undifferentiated features (81.9%, 95% CI%: 79.7-84.2%). A positive family history of gastric cancer was the most important risk factor associated with the development of gastric carcinoma in young individuals (pooled odds ratios 4.0, 95% CI: 2.8-5.2), followed by H. pylori infection (odds ratio 2.3; 95% CI: 1.4-3.2) and dietary and other lifestyle risk factors. DISCUSSION: Young-onset gastric carcinoma exhibits specific clinicopathological characteristics, with positive family history being the most important risk factor. Most of the patients were symptomatic at diagnosis. These findings could help to inform future strategies for the early detection of gastric carcinoma among young individuals.

Prevalence of the cagA Virulence Factor Varies by Race Among Helicobacter pylori -Infected Patients Undergoing Upper Endoscopy.

INTRODUCTION: We designed a race-conscious study to assess the presence of Helicobacter pylori v irulence factor cagA in a retrospective cohort of patients with active H. pylori infection. METHODS: We compared cagA status by race in gastric tissue samples from 473 patients diagnosed with active H. pylori infection from 2015 to 2019. RESULTS: H. pylori + Black patients were 2 times more likely to be cagA + than H. pylori + White patients (82% vs 36%, P < .0001). DISCUSSION: Presence of cagA is common among endoscopy patients with active H. pylori infection; appropriate testing and treatment of H. pylori can both reduce gastric cancer risk and address health disparities.

The Impact of Racial Disparities and the Social Determinants of Health on Esophageal and Gastric Cancer Outcomes.

Reducing long-standing inequities in gastric and esophageal cancers is a priority of patients, providers, and policy makers. Many social determinants of health influence risk factors for disease development, incidence, treatment, and outcomes of gastric and esophageal cancers.

Distinct characteristics of distant metastasis in early-onset gastric cancer patients compared to late-onset patients: An observational study.

Presently, there is limited understanding of the features of distant metastasis in early-onset gastric cancer (GC). To explore these disparities, a retrospective study utilizing the Surveillance, Epidemiology, and End Results (SEER) database was undertaken. The SEER database was utilized to extract patient data, and multivariate logistic regression analysis was employed to identify the risk factors associated with distant metastasis and liver metastasis. Propensity score matching (PSM) was used to compare the occurrence of liver metastasis among patients based on their age at diagnosis. The study included 2684 early-onset GC patients and 33,289 late-onset GC patients. Preliminary data analysis indicated that early-onset GC patients exhibited more aggressive characteristics such as poor cell differentiation, advanced T stage, and a higher incidence of distant metastasis, excluding liver metastasis. Multivariate logistic regression analysis identified younger age as an independent risk factor for distant metastasis, along with T stage, lymph node metastasis (LNM), and tumor size (>3 cm). Another regression analysis revealed that younger age, diffuse type, and female gender were protective factors against liver metastasis. Through PSM, 3276 early-onset GC patients were matched with an equal number of late-onset GC patients, revealing that patients with early-onset GC had fewer instances of liver metastasis but a higher prevalence of distant metastasis. Our findings suggest that early-onset serves as a protective factor against liver metastasis in GC, while it poses a risk for distant metastasis, likely influenced by the increased prevalence of diffuse-type GC in early-onset patients.

Autoimmune conditions and gastric cancer risk in a population-based study in the United Kingdom.

BACKGROUND: Although overall incidence of gastric cancer is decreasing, incidence has been increasing among young people in some Western countries. This trend may stem from the increase in autoimmune conditions. METHODS: A nested case-control study of gastric cancer in UK Clinical Practice Research Datalink. Up to ten cancer-free controls were matched to cases by age and sex. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for associations between analyzable autoimmune conditions (n = 34) and gastric cancer with Bonferroni correction. We evaluated associations between pernicious anaemia and other conditions. A meta-analysis of published prospective studies and ours was conducted. RESULTS: Among 6586 cases (1156 cardia, 1104 non-cardia, and 4334 overlapping/unspecified tumours) and 65,687 controls, any autoimmune condition was associated with gastric cancer (OR = 1.10; 95% CI: 1.01-1.20). Individuals with pernicious anaemia had higher gastric cancer risk than those without (OR = 2.75; 2.19-3.44). Among controls, pernicious anaemia was associated with seven other conditions (OR range: 2.21-29.80). The pooled estimate for any autoimmune condition and gastric cancer was 1.17 (1.14-1.21; n = 47,126 cases). CONCLUSION: Autoimmunity increases gastric cancer risk. Some autoimmune conditions may be indirectly associated with gastric cancer via pernicious anaemia. Pernicious anaemia could be considered for gastric cancer risk stratification and screening.

Retrospective Study of Claudin 18 Isoform 2 Prevalence and Prognostic Association in Gastric and Gastroesophageal Junction Adenocarcinoma.

PURPOSE: Claudin 18 isoform 2 (CLDN18.2) is an emerging biomarker and therapeutic target in gastric and gastroesophageal junction (G/GEJ) adenocarcinoma. This study aimed to obtain deeper understanding of CLDN18.2 positivity patterns, prognostic implications, and associations with various demographic, clinical, and molecular characteristics in G/GEJ adenocarcinoma. METHODS: Archived tumor tissue samples from 304 patients with G/GEJ adenocarcinoma in the United States were assessed for CLDN18.2 positivity by immunohistochemistry. CLDN18.2 positivity was defined as ≥50% or ≥75% of tumor cells with CLDN18 staining intensity ≥2+. CLDN18.2 positivity patterns were analyzed for association with prognosis and clinicopathologic/demographic characteristics. Where possible, CLDN18.2 positivity was analyzed for matched tissue samples to assess concordance between primary and metastatic tumors and concordance before and after chemotherapy. RESULTS: The overall prevalence of CLDN18.2-positive tumors (with ≥75% cutoff) was 44.4% (n = 135 of 304). CLDN18.2-positive tumors had a prevalence of 51.4% (n = 91 of 177) in gastric and 34.6% (n = 44 of 127) in GEJ adenocarcinoma. With a ≥50% cutoff, the prevalence of CLDN18.2-positive tumors was 64.4% (n = 114 of 177) in gastric adenocarcinoma and 44.9% (n = 57 of 127) in GEJ adenocarcinoma. There was no association between overall survival and CLDN18.2 positivity using either threshold. Statistically significant associations were noted between CLDN18.2 positivity and sex, histologic type of G/GEJ adenocarcinoma, and adenocarcinoma subtype (≥75% cutoff), and metastasis site and tumor grade (≥50% cutoff). The overall concordance of CLDN18.2 positivity (≥75% cutoff) was 73% (27 of 37) for matched primary versus metastatic tumor samples and 74% (29 of 39) for matched samples before and after chemotherapy. CONCLUSION: This study demonstrated that CLDN18.2 positivity did not correlate with survival in G/GEJ adenocarcinoma, consistent with published data. On the basis of matched sample analysis, CLDN18.2 appears to demonstrate >70% concordance as a biomarker. Observed correlations with certain patient/tumor characteristics warrant further study.

Chronic atrophic gastritis and risk of incident upper gastrointestinal cancers: a systematic review and meta-analysis.

BACKGROUND: Previous literature has explored the relationship between chronic atrophic gastritis (CAG) and isolated cancers within the upper gastrointestinal cancers; However, an integrative synthesis across the totality of upper gastrointestinal cancers was conspicuously absent. The research objective was to assess the relationship between CAG and the risk of incident upper gastrointestinal cancers, specifically including gastric cancer, oesophageal cancer, and oesophagogastric junction cancer. METHODS: Rigorous systematic searches were conducted across three major databases, namely PubMed, Embase and Web of Science, encompassing the timeline from database inception until August 10, 2023. We extracted the necessary odds ratio (OR) and their corresponding 95% confidence interval (CI) for subsequent meta-analysis. Statistical analyses were conducted using Stata 17.0 software. RESULTS: This meta-analysis included a total of 23 articles encompassing 5858 patients diagnosed with upper gastrointestinal cancers. CAG resulted in a statistically significant 4.12-fold elevated risk of incident gastric cancer (OR = 4.12, 95% CI 3.20-5.30). Likewise, CAG was linked to a 2.08-fold increased risk of incident oesophageal cancer (OR = 2.08, 95%CI 1.60-2.72). Intriguingly, a specific correlation was found between CAG and the risk of incident oesophageal squamous cell carcinoma (OR = 2.29, 95%CI 1.77-2.95), while no significant association was detected for oesophageal adenocarcinoma (OR = 0.62, 95%CI 0.17-2.26). Moreover, CAG was correlated with a 2.77-fold heightened risk of oesophagogastric junction cancer (OR = 2.77, 95%CI 2.21-3.46). Notably, for the same type of upper gastrointestinal cancer, it was observed that diagnosing CAG through histological methods was linked to a 33-77% higher risk of developing cancer compared to diagnosing CAG through serological methods. CONCLUSION: This meta-analysis indicated a two- to fourfold increased risk of gastric cancer, oesophageal cancer, and oesophagogastric junction cancer in patients with CAG. Importantly, for the same upper gastrointestinal cancer, the risk of incident cancer was higher when CAG was diagnosed histologically compared to serological diagnosis. Further rigorous study designs are required to explore the impact of CAG diagnosed through both diagnostic methods on the risk of upper gastrointestinal cancers.

Response to editorial: Gastric and pancreatic cancer trends in Spain.

This response to an editorial discusses recent trends in gastric and pancreatic cancer mortality in Spain. The authors acknowledge the contrasting trajectories - a decrease in gastric cancer and an increase in pancreatic cancer - and attribute them to differing causes. Public health measures, particularly H. pylori eradication, are credited for the decline in gastric cancer. The authors also present unpublished data showing a worrying rise in gastric cancer diagnoses among young men. They emphasize the need for continued monitoring, early detection strategies, and preventative measures to tackle both cancers, particularly focusing on pancreatic cancer research due to its rising mortality.

Diabetes and gastric cancer incidence and mortality in the Asia Cohort Consortium: A pooled analysis of more than a half million participants.

BACKGROUND: Evidence suggests a possible link between diabetes and gastric cancer risk, but the findings remain inconclusive, with limited studies in the Asian population. We aimed to assess the impact of diabetes and diabetes duration on the development of gastric cancer overall, by anatomical and histological subtypes. METHODS: A pooled analysis was conducted using 12 prospective studies included in the Asia Cohort Consortium. Among 558 981 participants (median age 52), after a median follow-up of 14.9 years and 10.5 years, 8556 incident primary gastric cancers and 8058 gastric cancer deaths occurred, respectively. Cox proportional hazard regression models were used to estimate study-specific hazard ratios (HRs) and 95% confidence intervals (CIs) and pooled using random-effects meta-analyses. RESULTS: Diabetes was associated with an increased incidence of overall gastric cancer (HR 1.15, 95% CI 1.06-1.25). The risk association did not differ significantly by sex (women vs men: HR 1.31, 95% CI 1.07-1.60 vs 1.12, 1.01-1.23), anatomical subsites (noncardia vs cardia: 1.14, 1.02-1.28 vs 1.17, 0.77-1.78) and histological subtypes (intestinal vs diffuse: 1.22, 1.02-1.46 vs 1.00, 0.62-1.61). Gastric cancer risk increased significantly during the first decade following diabetes diagnosis (HR 4.70, 95% CI 3.77-5.86), and decreased with time (nonlinear p < .01). Positive associations between diabetes and gastric cancer mortality were observed (HR 1.15, 95% CI 1.03-1.28) but attenuated after a 2-year time lag. CONCLUSION: Diabetes was associated with an increased gastric cancer incidence regardless of sex, anatomical subsite, or subtypes of gastric cancer. The risk of gastric cancer was particularly high during the first decade following diabetes diagnosis.

Stomach Cancer Prediction Model (SCoPM): An approach to risk stratification in a diverse U.S. population.

BACKGROUND AND AIMS: Population-based screening for gastric cancer (GC) in low prevalence nations is not recommended. The objective of this study was to develop a risk-prediction model to identify high-risk patients who could potentially benefit from targeted screening in a racial/ethnically diverse regional US population. METHODS: We performed a retrospective cohort study from Kaiser Permanente Southern California from January 2008-June 2018 among individuals age ≥50 years. Patients with prior GC or follow-up <30 days were excluded. Censoring occurred at GC, death, age 85 years, disenrollment, end of 5-year follow-up, or study conclusion. Cross-validated LASSO regression models were developed to identify the strongest of 20 candidate predictors (clinical, demographic, and laboratory parameters). Records from 12 of the medical service areas were used for training/initial validation while records from a separate medical service area were used for testing. RESULTS: 1,844,643 individuals formed the study cohort (1,555,392 training and validation, 289,251 testing). Mean age was 61.9 years with 53.3% female. GC incidence was 2.1 (95% CI 2.0-2.2) cases per 10,000 person-years (pyr). Higher incidence was seen with family history: 4.8/10,000 pyr, history of gastric ulcer: 5.3/10,000 pyr, H. pylori: 3.6/10,000 pyr and anemia: 5.3/10,000 pyr. The final model included age, gender, race/ethnicity, smoking, proton-pump inhibitor, family history of gastric cancer, history of gastric ulcer, H. pylori infection, and baseline hemoglobin. The means and standard deviations (SD) of c-index in validation and testing datasets were 0.75 (SD 0.03) and 0.76 (SD 0.02), respectively. CONCLUSIONS: This prediction model may serve as an aid for pre-endoscopic assessment of GC risk for identification of a high-risk population that could benefit from targeted screening.

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

Backgroud: 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. Materials and methods: 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. Results: 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. Conclusions: 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.