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The Lancet. Public Health Dec 2021Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported...
BACKGROUND
Helicobacter pylori infection is a major cause of non-cardia gastric cancer (NCGC), but its causal role in cardia gastric cancer (CGC) is unclear. Moreover, the reported magnitude of association with NCGC varies considerably, leading to uncertainty about population-based H pylori screening and eradication strategies in high-risk settings, particularly in China, where approximately half of all global gastric cancer cases occur. Our aim was to assess the associations of H pylori infection, both overall and for individual infection biomarkers, with the risks of NCGC and CGC in Chinese adults.
METHODS
A case-cohort study was done in adults from the prospective China Kadoorie Biobank study, aged 30-79 years from ten areas in China (Qingdao, Haikou, Harbin, Suzhou, Liuzhou, Henan, Sichuan, Hunan, Gansu, and Zhejiang), and included 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants who were cancer-free and alive within the first two years since enrolment in 2004-08. H pylori biomarkers were measured in stored baseline plasma samples using a sensitive immunoblot assay (HelicoBlot 2.1), with adapted criteria to define H pylori seropositivity. Cox regression was used to estimate adjusted hazard ratios (HRs) for NCGC and CGC associated with H pylori infection. These values were used to estimate the number of gastric cancer cases attributable to H pylori infection in China.
FINDINGS
Of the 512 715 adults enrolled in the China Kadoorie Biobank between June, 2004, and July, 2008, 500 incident NCGC cases, 437 incident CGC cases, and 500 subcohort participants were selected for analysis. The seroprevalence of H pylori was 94·4% (95% CI 92·4-96·4) in NGCG, 92·2% (89·7-94·7) in CGC, and 75·6% (71·8-79·4) in subcohort participants. H pylori infection was associated with adjusted HRs of 5·94 (95% CI 3·25-10·86) for NCGC and 3·06 (1·54-6·10) for CGC. Among the seven individual infection biomarkers, cytotoxin-associated antigen had the highest HRs for both NCGC (HR 4·41, 95% CI 2·60-7·50) and CGC (2·94, 1·53-5·68). In this population, 78·5% of NCGC and 62·1% of CGC cases could be attributable to H pylori infection. H pylori infection accounted for an estimated 339 955 cases of gastric cancer in China in 2018.
INTERPRETATION
Among Chinese adults, H pylori infection is common and is the cause of large numbers of gastric cancer cases. Population-based mass screening and the eradication of H pylori should be considered to reduce the burden of gastric cancer in high-risk settings.
FUNDING
Cancer Research UK, Wellcome Trust, UK Medical Research Council, British Heart Foundation, Kadoorie Charitable Foundation, National Key Research and Development Program of China, and National Natural Science Foundation of China.
Topics: Aged; Biological Specimen Banks; Biomarkers; Cardia; China; Cohort Studies; Female; Helicobacter Infections; Helicobacter pylori; Humans; Immunoblotting; Male; Middle Aged; Odds Ratio; Proportional Hazards Models; Prospective Studies; Seroepidemiologic Studies; Stomach Neoplasms
PubMed: 34838195
DOI: 10.1016/S2468-2667(21)00164-X -
Cancer Medicine Oct 2019Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In... (Review)
Review
Recent decades have seen an alarming increase in the incidence of cardia gastric adenocarcinoma (CGA) while noncardia gastric adenocarcinoma (NCGA) has decreased. In 2012, 260 000 CGA cases (age-standardised rate (ASR); 3.3/100 000) and 691 000 NCGA cases (ASR; 8.8/100 000) were reported worldwide. Compared with women, men had greater rates for both the subsites, especially for CGA. Recently, four molecular subtypes of GC have been proposed by the Cancer Genome Atlas (TCGA) and the Asian Cancer Research Group (ACRG); however, these classifications do not take into account predisposing germline variants and their possible interaction with somatic alterations in carcinogenesis. The etiology of adenocarcinoma of the cardia and the gastroesophageal junction (GEJ) is not known. It is thought that CGA is distinct from adenocarcinomas located in the esophagus or distal stomach, both epidemiologically and biologically. Moreover, CGA is often identified in the advanced stage having a poor prognosis. Therefore, understanding the risk and the role of predisposing factors in etiology of CGA can inform clinical practice and counseling for risk reduction. In this paper, we showed that GC family history, lifestyle, demographics, gastroesophageal reflux disease, Helicobacter pylori infection, and multiple genetic and epigenetic risk factors as well as several predisposing conditions may underlie susceptibility to CGA. However, several genome-wide association studies (GWASs) should be conducted to identify novel high-penetrance genes and pathways as well as causal germline variants predisposing to CGA. They must include different ethnic groups, especially from high-incidence countries for CGA, because some risk loci are ancestry-specific. In parallel, statistical methods can be developed to identify cancer predisposition genes (CPGs) from tumor sequencing data. It is also necessary to find novel long noncoding RNAs related to the risk of CGA. Taken altogether, new cancer risk prediction models, including all genetic and nongenetic factors influencing risk, should be developed to facilitate risk assessment, disease prevention, and early diagnosis and intervention of CGA in the future.
Topics: Adenocarcinoma; Cardia; Gastroesophageal Reflux; Genetic Predisposition to Disease; Health Behavior; Helicobacter Infections; Humans; MicroRNAs; RNA, Long Noncoding; Risk Factors; Stomach Neoplasms
PubMed: 31448582
DOI: 10.1002/cam4.2497 -
Journal of Cellular and Molecular... Aug 2020Gastric cancer (GC) is a heterogeneous tumour with numerous differences of epidemiologic and clinicopathologic features between cardia cancer and non-cardia cancer....
Gastric cancer (GC) is a heterogeneous tumour with numerous differences of epidemiologic and clinicopathologic features between cardia cancer and non-cardia cancer. However, few studies were performed to construct site-specific GC prognostic models. In this study, we identified site-specific GC transcriptomic prognostic biomarkers using genetic algorithm (GA)-based support vector machine (GA-SVM) and GA-based Cox regression method (GA-Cox) in the Cancer Genome Atlas (TCGA) database. The area under time-dependent receive operating characteristic (ROC) curve (AUC) regarding 5-year survival and concordance index (C-index) was used to evaluate the predictive ability of Cox regression models. Finally, we identified 10 and 13 prognostic biomarkers for cardia cancer and non-cardia cancer, respectively. Compared to traditional models, the addition of these site-specific biomarkers could notably improve the model preference (cardia: AUC vs AUC = 0.720 vs 0.899, P = 8.75E-08; non-cardia: AUC vs AUC = 0.798 vs 0.994, P = 7.11E-16). The combined nomograms exhibited superior performance in cardia and non-cardia GC survival prediction (C-index = 0.816; C-index = 0.812). We also constructed a user-friendly GC site-specific molecular system (GC-SMS, https://njmu-zhanglab.shinyapps.io/gc_sms/), which is freely available for users. In conclusion, we developed site-specific GC prognostic models for predicting cardia cancer and non-cardia cancer survival, providing more support for the individualized therapy of GC patients.
Topics: Algorithms; Biomarkers, Tumor; Cardia; Case-Control Studies; Computational Biology; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humans; Male; Nomograms; Prognosis; ROC Curve; Stomach Neoplasms; Survival Rate; Transcriptome
PubMed: 32649057
DOI: 10.1111/jcmm.15618 -
Journal of Gastrointestinal and Liver... Dec 2021Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly...
BACKGROUND AND AIMS
Symptoms of patients with gastric cancer (GC) are often unspecific and differences in symptoms between patients with cardia and non-cardia GC have been poorly investigated. We aimed to characterize symptoms of patients with cardia and non-cardia GC.
METHODS
Patients with cardia (Siewert type II and III) and non-cardia GC were recruited in the German multicenter cohort of the Gastric Cancer Research (staR) study between 2013 and 2017. Alarm, dyspeptic and reflux symptoms at the time of presentation were documented using a self-administered questionnaire.
RESULTS
A completed self-administered questionnaire was available for 568/759 recruited patients (132 cardia GC, 436 non-cardia GC, male 61%, mean age 64 years). Dyspeptic symptoms were more common in patients with non-cardia GC (69.0 vs. 54.5%, p=0.0024). Cardia GC patients reported more frequently alarm symptoms (69.7 vs. 44.7%, p<0.0001), and were more likely to have Union for International Cancer Control (UICC) stage III-IV (54.1vs. 38.9%, p=0.0034). Especially, dysphagia and weight loss were more common in patients with cardia GC (49.2 vs. 6.4 %, p<0.0001 and 37.1 vs. 25.7%, p=0.02, respectively). No differences between the two groups were observed with respect to reflux symptoms. Patients with alarm symptoms were more likely to have UICC stage III-IV at presentation (69.4 vs. 42.9%, p<0.0001).
CONCLUSIONS
In clinical practice the symptom pattern at presentation may serve as a hint for tumor localization. Despite the fact that they are common in the general population, dyspeptic symptoms offer a chance for earlier GC detection. Thus, in patients with dyspeptic symptoms who fail empiric approaches, endoscopy should not be delayed.
Topics: Cardia; Endoscopy; Humans; Male; Middle Aged; Prevalence; Stomach Neoplasms
PubMed: 34752588
DOI: 10.15403/jgld-3795 -
Indian Pediatrics Sep 2016Achalasia is extremely rare in infants.
BACKGROUND
Achalasia is extremely rare in infants.
CASE CHARACTERISTICS
We report three infants of age 9, 7 and 12 months, who presented with recurrent non-bilious vomiting, repeated chest infection and severe failure to thrive. Diagnosis of achalasia cardia was confirmed on contrast-swallow study. Hellers cardiomyotomy with fundoplication led to complete symptomatic relief, and weight-gain on follow-up.
MESSAGE
Achalasia cardia is often misdiagnosed as gastroesophageal reflux disease which leads to significant delay in diagnosis and increased morbidity.
Topics: Cardia; Diagnosis, Differential; Esophageal Achalasia; Humans; Infant; Male
PubMed: 27771653
DOI: 10.1007/s13312-016-0940-y -
Annals of Oncology : Official Journal... Feb 2012In order to provide a precise quantification of the association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, we conducted a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
In order to provide a precise quantification of the association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, we conducted a meta-analysis of available data.
PATIENTS AND METHODS
We identified 20 case-control and 4 cohort studies, including a total of 5500 cases. We derived meta-analytic estimates using random-effects models, taking into account correlation between estimates, and we carried out a dose-risk analysis using nonlinear random-effects meta-regression models.
RESULTS
The relative risk (RR) for drinkers versus nondrinkers was 0.96 [95% confidence interval (CI) 0.85-1.09] overall, 0.87 (95% CI 0.74-1.01) for esophageal adenocarcinoma and 0.89 (95% CI 0.76-1.03) for gastric cardia adenocarcinoma. Compared with nondrinkers, the pooled RRs were 0.86 for light (≤ 1 drink per day), 0.90 for moderate (1 to < 4 drinks per day), and 1.16 for heavy (≥ 4 drinks per day) alcohol drinking. The dose-risk model found a minimum at 25 g/day, and the curve was < 1 up to 70 g/day.
CONCLUSIONS
This meta-analysis provides definite evidence of an absence of association between alcohol drinking and esophageal and gastric cardia adenocarcinoma risk, even at higher doses of consumption.
Topics: Adenocarcinoma; Alcohol Drinking; Cardia; Case-Control Studies; Cohort Studies; Esophageal Neoplasms; Female; Humans; Male; Regression Analysis; Risk; Stomach Neoplasms
PubMed: 21551004
DOI: 10.1093/annonc/mdr136 -
Clinical Gastroenterology and... Jan 2020Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM)...
BACKGROUND & AIMS
Endoscopic eradication therapy (EET) for Barrett's esophagus (BE) has unclear effects on the gastric cardia. We investigated the prevalence of intestinal metaplasia (IM) and dysplasia in the cardia after complete eradication of IM (CEIM) and the incidence of newly diagnosed cardia IM or dysplasia after EET.
METHODS
We performed a prospective study, from 2013 through 2016, of patients with previously successful EET undergoing surveillance after CEIM (cross-sectional group) and treatment-naïve patients with BE undergoing EET (longitudinal group). Standard biopsies were collected from multiple levels in the cardia and analyzed histologically. We calculated the prevalence (cross-sectional group) and the incidence (longitudinal group) of cardia IM or dysplasia after EET.
RESULTS
Of the 116 patients in the cross-sectional group, 17 (15%) had cardia IM or dysplasia after CEIM: 12 patients had IM, 2 patients were indefinite for dysplasia, and 3 patients had low-grade dysplasia. Cardia IM or dysplasia were most commonly found at the tops of gastric folds. Among 42 subjects in the longitudinal group, the pre-treatment prevalence of cardia IM or dysplasia was 28.5% (3 with non-dysplastic IM, 9 with dysplastic IM, 1 indefinite for dysplasia, 2 with low-grade dysplasia, 3 with high-grade dysplasia, and 3 with intramucosal cancer). All achieved CEIM. The incidence of cardia IM or dysplasia was 11.9% after 18 months of follow up. IM or dysplasia was more higher in the cardia after CEIM than in the tubular esophagus (P < .01).
CONCLUSIONS
In a prospective study, we found that cardia dysplasia becomes less, not more, common, after successful EET; recurrence of IM or dysplasia was more frequent in the cardia than the esophagus. Patients with BE undergoing EET should have careful examination of the cardia, with a single set of surveillance biopsies at the top of the gastric folds.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Barrett Esophagus; Biopsy; Cardia; Esophagus; Female; Gastroscopy; Humans; Incidence; Male; Metaplasia; Middle Aged; Neoplasm Recurrence, Local; Population Surveillance; Prevalence; Prospective Studies; Recurrence; Stomach; Stomach Neoplasms
PubMed: 31077822
DOI: 10.1016/j.cgh.2019.04.065 -
BMC Gastroenterology Dec 2020Gastric cancer is more common in men than in women, but underlying reasons have not been completely understood. This study aimed to assess patterns of the sex difference...
BACKGROUND
Gastric cancer is more common in men than in women, but underlying reasons have not been completely understood. This study aimed to assess patterns of the sex difference in the incidence of gastric cancer in the United States.
METHODS
Using data from 13 cancer registries in the Surveillance, Epidemiology, and End Results Program, we analyzed the age-specific sex difference in the incidence of gastric cancer by ethnicity, anatomic site and histological type in the United States during 1992-2014. We assessed the temporal trends in the sex differences in the incidence of gastric cancer during the study period.
RESULTS
The male-to-female incidence ratio of cardia cancer increased with age until peaking at ages 55-69 years and decreased thereafter, while the ratio for non-cardia gastric cancer increased with age before ages < 60 years and remained stable onwards. The age-specific patterns in the sex difference of gastric cancer incidence varied between intestinal and diffuse histological types. The sex difference in the incidence of cardia cancer remained relatively stable except for that the absolute difference between the sexes in whites decreased on average by 0.8% per year from 1992 to 2014. The absolute incidence difference between the sexes in non-cardia gastric cancer decreased over time in whites, blacks, and Asian and Pacific islanders by approximately 4% per year. The male-to-female incidence ratio of non-cardia gastric cancer decreased over time in whites and blacks, but remained relatively stable in Asian and Pacific islanders.
CONCLUSIONS
Both extrinsic and intrinsic factors may have contributed to the sex difference in gastric cancer. Sex hormones may play a role in the development of cardia cancer and intestinal type of gastric cancer.
Topics: Aged; Cardia; Female; Humans; Incidence; Male; Middle Aged; SEER Program; Sex Characteristics; Stomach Neoplasms; United States
PubMed: 33308167
DOI: 10.1186/s12876-020-01551-1 -
Saudi Journal of Gastroenterology :... 2018
Topics: Cardia; Endoscopy; Esophageal Achalasia; Humans; Myotomy
PubMed: 29451176
DOI: 10.4103/sjg.SJG_488_17 -
Gastroenterology Aug 2019In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous... (Review)
Review
In patients with Barrett's esophagus (BE), metaplastic columnar mucosa containing epithelial cells with gastric and intestinal features replaces esophageal squamous mucosa damaged by gastroesophageal reflux disease. This condition is estimated to affect 5.6% of adults in the United States, and is a major risk factor for esophageal adenocarcinoma. Despite the prevalence and importance of BE, its pathogenesis is incompletely understood and there are disagreements over the cells of origin. We review mechanisms of BE pathogenesis, including transdifferentiation and transcommitment, and discuss potential cells of origin, including basal cells of the squamous epithelium, cells of esophageal submucosal glands and their ducts, cells of the proximal stomach, and specialized populations of cells at the esophagogastric junction (residual embryonic cells and transitional basal cells). We discuss the concept of metaplasia as a wound-healing response, and how cardiac mucosa might be the precursor of the intestinal metaplasia of BE. Finally, we discuss shortcomings in current diagnostic criteria for BE that have important clinical implications.
Topics: Adenocarcinoma; Barrett Esophagus; Cardia; Cell Transdifferentiation; Disease Progression; Epithelial Cells; Esophageal Mucosa; Esophageal Neoplasms; Esophagogastric Junction; Gastric Mucosa; Humans; Metaplasia; United States; Wound Healing
PubMed: 31082367
DOI: 10.1053/j.gastro.2019.03.072