Incidence Of Esophageal Adenocarcinoma Research Articles

AGA Clinical Practice Update on the Utility of Endoscopic Submucosal Dissection in T1b Esophageal Cancer: Expert Review

Mo1217 ENDOSCOPIC SUBMUCOSAL DISSECTION IS ASSOCIATED WITH LESS PATHOLOGIC UNCERTAINTY THAN ENDOSCOPIC MUCOSAL RESECTION IN DIAGNOSING AND STAGING BARRET'S RELATED NEOPLASIA

e15536 Background: Squamous cell carcinoma and adenocarcinoma represent approximately 95% of malignant tumors of the esophagus. For most cases of the 20th century, squamous cell carcinoma was the predominant lineage. In the 1960s, squamous cell carcinoma accounted for more than 90% of all esophageal tumors in the United States of America, and adenocarcinoma was considered so uncommon that some oncological associations questioned its existence. However over time the incidence of esophageal adenocarcinoma (predominantly in the distal esophagus and gastroesophageal junction) has increased dramatically in Western countries, with adenocarcinoma now causing more than 60% of all esophageal cancers in the United States of America, unlike the rest of the world, where squamous cell carcinoma continues to predominate. Squamous cell carcinoma and adenocarcinoma differ in a significant number of clinical features, including tumor location and predisposing factors. Smoking and alcoholism are major risk factors for the development of squamous cell carcinoma, while the Barrett's esophagus with intestinal metaplasia (a complication of gastroesophageal reflux disease), obesity, and smoking are the risk factors related to adenocarcinoma of the esophagus. Objectives: To determine the incidence of esophageal adenocarcinoma in Mexico and its main characteristics, such as epidemiology, histological type and main risk factors. Methods: A descriptive analysis was conducted in which the histological type, age of diagnosis, location, age of the patients and risk factors were compared. Results: Average age on the studied population was 67.4 years (minimum 37, maximum 91); 74.3% of the subjects were male and 20.4%, female. It was found that the predominant histological type was Adenocarcinoma in 40.7% against 28.3% of the Epidermoid. Average age of diagnosis was at 65.88 years (minimum 37, maximum 89). In frequency of localization, lower third in 22.1%, union GE in 20.4%, middle third in 15%, and upper third in 12.4%). The predominant risk factors in our study were smoking (31%), alcoholism (36.3%) and GERD (12.4%). Conclusions: Oesophageal adenocarcinoma continues to be the most prevalent presentation of esophageal cancer in our population, despite epidemiological changes over time.

e15535 Background: The incidence of Esophageal Adenocarcinoma (EAC) has risen in the western world but response rates to chemotherapy are low and survival is poor. Increased molecular understanding is needed to develop novel treatments. Methods: Transcriptional profiling of 274 treatment naïve EAC biopsies was performed using the Almac Diagnostics Xcel array™. All patients received platinum-based neo-adjuvant chemotherapy prior to surgical resection at four United Kingdom centers between 2004-2012. Semi-supervised clustering was performed followed by functional enrichment using DAVID. Cluster membership was assessed for independence of prognostic factors using Cox proportional hazards. Candidate targets were identified by siRNA screening in OE33 cells. Treatment with the survivin inhibitor, YM155 in EAC cell lines was also assessed. Results: Semi-supervised hierarchical clustering identified two groups with significant differences in RFS [HR = 0.54 (0.29-0.99), p = 0.05] and OS [HR = 0.52 (0.28-0.96), p = 0.04]. There were significant associations between the clusters and both nodal and TNM downstaging but not with pathological response. The PI3K-AKT, p53, tight junction and HIF-1 signaling pathways were upregulated in the poor prognostic group. Eighty-four genes were selected and taken forward in a functional genomic siRNA screen. Twenty-seven genes showed a significant reduction in viability following siRNA-mediated knockdown and further verification resulted in twelve candidate genes. Finally, target knockdown in seven EAC cell lines resulted in four interrelated hits- BIRC5, JAK1, OSMR and SLC2A1. Knock down of BIRC5 (Survivin) induced apoptosis, as evidenced by PARP cleavage, in both the parental OE33 and cisplatin-resistant OE33CDDPR cell lines. YM155, a survivin inhibitor, is shown to induce apoptosis at nanomolar concentrations across a panel of parental and cisplatin-resistant EAC cell lines and further mechanistic work is ongoing. Conclusions: We have performed clustering of a large transcriptomic dataset and defined a poor prognostic group of EAC patients. We identified Survivin (BIRC5) as a mediator of cisplatin resistance in EAC and a potential novel drug target. Further pre-clinical and clinical work to assess the benefit of survivin inhibition in EAC is warranted.

The incidence of esophageal adenocarcinoma (EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus (BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux (GER), male sex, older age, central obesity, tobacco smoking, Helicobacter pylori (H. pylori) eradication, and the administration of proton pump inhibitors (PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes, Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type I microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type II microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

Purpose: The incidence of esophageal adenocarcinoma (EAC) has increased by 700% in Western countries over the last 30 years. Although clinical guidelines call for endoscopic surveillance for EAC among high-risk populations, fewer than 5% of new EAC patients are under surveillance at the time of diagnosis. We studied the accuracy of combined cytopathology and MUC2 immunohistochemistry (IHC) for screening of Intestinal Metaplasia (IM), dysplasia and EAC, using specimens collected from the EsophaCap swallowable encapsulated cytology sponge from Canada and United States.Patients and methods: By comparing the EsophaCap cytological diagnosis with concurrent endoscopic biopsies performed on the same patients in 28 cases, we first built up the cytology diagnostic categories and criteria. Based on these criteria, 136 cases were evaluated by both cytology and MUC2 IHC with blinded to patient biopsy diagnosis.Results: We first set up categories and criteria for cytological diagnosis of EscophaCap samples. Based on these, we divided our evaluated cytological samples into two groups: non-IM group and IM or dysplasia or adenocarcinoma group. Using the biopsy as our gold standard to screen IM, dysplasia and EAC by combined cytology and MUC2 IHC, the sensitivity and specificity were 68% and 91%, respectively, which is in the range of clinically useful cytological screening tests such as the cervical Pap smear.Conclusions: Combined EsophaCap cytology and MUC2 IHC could be a good screening test for IM and Beyond.

Sa1149 – Incidence of High Grade Dysplasia (HGD) and Esophageal Adenocarcinoma (EAC) in Patients with Irregular Z Line

To investigate factors predictive of progression from nondysplastic Barrett esophagus (NDBE) or low-grade dysplasia (LGD) to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) using a large, prospective cohort of patients, wherein all esophageal biopsies undergo expert gastrointestinal pathologist review. Efficacy and cost-effectiveness of endoscopic surveillance to detect incident EAC in the setting of Barrett esophagus (BE), particularly in NDBE patients, is questioned. Previous studies have reported factors predictive of progression to EAC to guide surveillance intervals, but their strength is limited by small sample size and absence of expert gastrointestinal pathologist involvement in esophageal biopsy review. NDBE and LGD subjects were identified from a prospective registry in a tertiary care center. "Progressors" were BE subjects who developed HGD/EAC>12 months after the initial NDBE or LGD diagnosis. Cox proportional hazards model were used to identify predictors of progression. In total, 318 with NDBE and 301 with BE-LGD (mean age, 62.6 y, 85% male) were included. The mean follow-up was 5.3 years. The 7 NDBE and 21 LGD subjects progressed to HGD/EAC. BE length [hazards ratio (HR), 1.16; 95% confidence interval (CI), 1.03-1.29], presence of nodularity (HR, 4.98; 95% CI, 1.80-11.7), and baseline LGD (HR, 2.57; 95% CI, 1.13-6.57) were significant predictors of progression on multivariate analysis. In this well-defined cohort of NDBE and BE-LGD subjects, BE length, presence of LGD, and nodularity were independent predictors of progression to HGD/EAC. These factors may aid in identifying high-risk patients who may benefit from closer endoscopic surveillance/therapy.

Risk stratification in patients with Barrett's esophagus (BE) to prevent the development of esophageal adenocarcinoma (EAC) is an unsolved task. The incidence of EAC and BE is increasing and patients are still at unknown risk. BarrettNET is an ongoing multicenter prospective cohort study initiated to identify and validate molecular and clinical biomarkers that allow a more personalized surveillance strategy for patients with BE. For BarrettNET participants are recruited in 20 study centers throughout Germany, to be followed for progression to dysplasia (low-grade dysplasia or high-grade dysplasia) or EAC for>10 years. The study instruments comprise self-administered epidemiological information (containing data on demographics, lifestyle factors, and health), as well as biological specimens, i.e., blood-based samples, esophageal tissue biopsies, and feces and saliva samples. In follow-up visits according to the individual surveillance plan of the participants, sample collection is repeated. The standardized collection and processing of the specimen guarantee the highest sample quality. Via a mobile accessible database, the documentation of inclusion, epidemiological data, and pathological disease status are recorded subsequently. Currently the BarrettNET registry includes 560 participants (23.1% women and 76.9% men, aged 22-92 years) with a median follow-up of 951 days. Both the design and the size of BarrettNET offer the advantage of answering research questions regarding potential causes of disease progression from BE to EAC. Here all the integrated methods and materials of BarrettNET are presented and reviewed to introduce this valuable German registry.

Higher clinical suspicion is needed for prompt diagnosis of esophageal adenocarcinoma in young patients

Purpose: The rapidly rising incidence of esophageal adenocarcinoma (EAC), which is usually diagnosed late with a poor prognosis, has become a growing problem. This study investigated the potential transcription factor (TF)-related molecular mechanisms of EAC by using bioinformatics analysis and qRT-PCR validation.Methods: Expression profile datasets for mRNAs (GSE92396, GSE13898, GSE26886 and GSE1420) and miRNAs (GSE16456) were downloaded from the GEO database. Overlapping differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) were identified through integrative analysis. Then, a TF-miRNA-mRNA network was constructed based on bioinformatics data from the TRRUST, TRED and miRTarBase database. Furthermore, overall survival analysis for the mRNAs and miRNAs in the TF-miRNA-mRNA network was performed with data from TCGA, and qRT-PCR was used to validate the results.Results: A total of 294 overlapping DEGs were identified in EAC tissues compared to normal tissues, including 181 downregulated and 113 upregulated genes. Then, 16 TFs that could target the DEGs and were related to cancer were predicted based on public databases, and 41 DEGs that could be targeted were identified as key genes. Additionally, 12 DEMs were predicted through miRTarBase to be associated with the key genes, and TP53-(miR-125b)-ID2 and JUN-(miR-30a)-IL1A from the TF-miRNA-mRNA network were identified to potentially play significant roles in EAC. Furthermore, CCL20, IL1A, ABCC3, hsa-miR-23b, and hsa-miR-191, which are involved in the TF-miRNA-mRNA network, were found to be significantly associated with patient survival in EAC. Finally, the expression of a miRNA-mRNA pair (hsa-miR-30a-5p and IL1A) was revealed to be correlated with prognosis.Conclusion: In this study, a TF-miRNA-mRNA network was constructed to analyze the potential molecular mechanisms of EAC. Key genes and miRNAs associated with patient survival were identified, which may reveal promising approaches for EAC diagnosis and therapy.

In Japan, the incidence of esophageal adenocarcinoma (EAC) and esophagogastric junction (EGJ) adenocarcinoma is expected to increase and that of gastric adenocarcinoma (GAC) is expected to decrease due to Westernization of the diet and the decreasing prevalence of Helicobacter pylori infection. However, few reports about these trends have included the latest data, and no reports about the time trend in the incidence of EGJ adenocarcinoma have focused on the etiologies (gastric cardia adenocarcinoma or EAC, including Barrett's adenocarcinoma). We therefore investigated the time trends in the incidence of these cancers by including the latest data. First, we investigated the time trends in EAC and GAC using population-based cancer registry data in Osaka Prefecture (1985-2014). We then investigated the time trend in superficial EGJ adenocarcinoma with clinicopathological features at Osaka International Cancer Institute (2006-2017). From 1985 to 2014 in Osaka Prefecture, the incidence of EAC gradually increased in both sexes, while that of GAC in men did not significantly change and that in women decreased. The ratio of the EAC/GAC incidence increased 3.5 times in men and 1.8 times in women. In the secondary time trend survey for EGJ adenocarcinoma, the numbers of patients with endoscopic Barrett's esophagus and those without gastric mucosal atrophy increased, and the number of patients with lesions located above the EGJ line and histologically diagnosed as Barrett's adenocarcinoma increased. The incidence of EAC and superficial EGJ adenocarcinoma with characteristics similar to those of EAC, including Barrett's adenocarcinoma, might be increasing.

BackgroundBarrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) incidence has been increasing in the United States for greater than 30 years. For the majority of EAC patients, treatment is limited and prognosis poor. Doublecortin like kinase-1 (DCLK1) is a cancer stem cell marker with elevated expression in BE patients with high grade dysplasia and/or EAC. This prospective cohort study was designed to compare serum DCLK1 levels before and after EAC treatment with endoscopic mucosal resection (EMR) and/or radio-frequency ablation (RFA).MethodsBarrett’s esophagus patients with low or high-grade dysplasia (n = 9) and EAC patients (Stage I/II) eligible for treatment were enrolled (n = 14). Serum was obtained at enrollment and at end of treatment (EoT) where possible (n = 6). Normal control samples (n = 5) were obtained from patients with normal upper endoscopies. Serum was analyzed for DCLK1 protein content by ELISA. Kruskal-Wallis, Mann Whitney U, Pearson correlation, and Receiver Operating Characteristic tests were used to analyze the data.ResultsSerum DCLK1 levels were increased by > 50% in Barrett’s Esophagus (n = 9) and EAC patients (n = 14) vs controls (n = 5, p = 0.0007). These levels were reduced > 50% at EoT compared to EAC (p = 0.033). Although age was significantly lower in controls, this factor was not statistically related to DCLK1 serum levels (p = 0.66).ConclusionsEAC treatment results in significantly decreased serum DCLK1 levels, suggesting that DCLK1 may be useful as a non-invasive disease regression biomarker following treatment.ImpactBiomarkers for EAC therapeutic response have been poorly studied and no reliable marker has been discovered thus far. These results demonstrate that DCLK1 may have potential as a circulating biomarker of the response to therapy in EAC, which could be used to improve patient outcomes.

71 Background: Esophageal adenocarcinoma (EAC) is the sixth most common cause of cancer-related deaths worldwide. It commonly arises in the setting of reflux disease and Barett’s esophagus. It remains incurable and holds a poor prognosis. Dissecting the genetic signature of EAC can pave new therapeutic avenues. Methods: We employed our Search Tag Analyze Resource (STARGEO) platform to conduct meta-analysis using the National Center for Biotechnology’s (NCBI) Gene Expression Omnibus (GEO). We tagged 151 tumor samples from EAC patients and 62 normal esophageal samples as a control. We then analyzed the signature in Ingenuity Pathway Analysis, restricting genes that showed statistical significance (p < 0.05) and an absolute experimental log ratio greater than 0.15 between tumor and control. Results: Our analysis revealed granulocyte adhesion and diapedesis and FXR/RXR signaling as top canonical pathways. TGFB1, TNF, and beta-estradiol were top upstream regulators with predicted activation. TGFB1 and TNF expression have been correlated with poor prognosis in EAC. Also, beta-estradiol has tumorigenic activity in several cancers but has not been investigated in EAC. Among the top upregulated genes were oncogenic genes such as tetraspanin 8, the antiapoptotic factor OLFM4, and the protease cathepsin E (CTSE). SPINK1, a trypsin inhibitor with recently suggested role in cancer, and the choline transporter SLC44A4, a drug target for pancreatic cancer, were also upregulated. The most downregulated genes included alcohol dehydrogenase 7, associated with EAC in alcohol-drinkers, and the pro-apoptotic gene CRCT1. We also found downregulation of the serine peptidase inhibitor SPINK7. SPINK7 is involved in maintaining epithelial-barrier integrity and is implicated in eosinophilic esophagitis pathogenesis. Lastly, there was downregulation of the candidate tumor suppressor gene transglutaminase 3. Conclusions: Despite screening efforts, EAC incidence and mortality continues to increase as does the need for better treatment. This meta-analysis defines the significant gene expression changes within causal disease processes to provide markers for detection, prognostic insight, and therapeutic value for EAC.

BackgroundThe incidence of esophageal adenocarcinoma (EAC) is rising rapidly in the US and Western countries. The development of Barrett’s esophagus (BE) and its progression to EAC have been linked to chronic gastroesophageal reflux disease (GERD). Exposure of BE and EAC cells to acidic bile salts (ABS) in GERD conditions induces high levels of oxidative stress and DNA damage. In this study, we investigated the role of insulin-like growth factor binding protein 2 (IGFBP2) in regulating ABS-induced DNA double-strand breaks.MethodsReal-time RT-PCR, western blot, immunohistochemistry, immunofluorescence, co-immunoprecipitation, flow cytometry, and cycloheximide (CHX) chase assays were used in this study. To mimic GERD conditions, a cocktail of acidic bile salts (pH 4) was used in 2D and 3D organotypic culture models. Overexpression and knockdown of IGFBP2 in EAC cells were established to examine the functional and mechanistic roles of IGFBP2 in ABS-induced DNA damage.ResultsOur results demonstrated high levels of IGFBP2 mRNA and protein in EAC cell lines as compared to precancerous Barrett’s cell lines, and IGFBP2 is frequently overexpressed in EACs (31/57). Treatment of EAC cells with ABS, to mimic GERD conditions, induced high levels of IGFBP2 expression. Knocking down endogenous IGFBP2 in FLO1 cells (with constitutive high levels of IGFBP2) led to a significant increase in DNA double-strand breaks and apoptosis, following transient exposure to ABS. On the other hand, overexpression of exogenous IGFBP2 in OE33 cells (with low endogenous levels of IGFBP2) had a protective effect against ABS-induced double-strand breaks and apoptosis. We found that IGFBP2 is required for ABS-induced nuclear accumulation and phosphorylation of EGFR and DNA-PKcs, which are necessary for DNA damage repair activity. Using co-immunoprecipitation assay, we detected co-localization of IGFBP2 with EGFR and DNA-PKcs, following acidic bile salts treatment. We further demonstrated, using cycloheximide chase assay, that IGFBP2 promotes EGFR protein stability in response to ABS exposure.ConclusionsIGFBP2 protects EAC cells against ABS-induced DNA damage and apoptosis through stabilization and activation of EGFR - DNA-PKcs signaling axis.

The incidence of esophageal adenocarcinoma is rapidly increasing in Western countries. This is despite the introduction of sophisticated endoscopic techniques and our ability to readily monitor the presumed precursor lesion known as Barrett's esophagus. Preemptive approaches, including radiofrequency ablation (RFA), and photodynamic therapy (PDT) for Barrett's esophagus and dysplasia are achieving dramatic initial results. Although the long-term efficacy of these nonspecific ablative therapies is awaiting longitudinal studies, reports of recurrences are increasing. More targeted therapies, particularly directed at the stem cells of Barrett's esophagus, demand knowing the origin of this intestinal metaplasia (IM). The prevailing concept holds that Barrett's esophagus arises from the "transcommitment" of esophageal stem cells to produce an intestine-like epithelium. An alternative explanation derives from the discovery of a discrete population of residual embryonic cells (RECs) existing at the gastroesophageal junction in normal individuals that expands and colonizes regions of the esophagus denuded by chronic reflux. These RECs form IM within days of esophageal injury, suggesting a novel mechanism of tumorigenesis.A corollary of this work is that the Barrett's stem cell is distinct from that of the squamous epithelium and, once identified, will form the basis of new preemptive strategies for addressing Barrett's and its related neoplasia.

Constitutively Higher Level of GSTT2 in Esophageal Tissues From African Americans Protects Cells Against DNA Damage

The incidence of esophageal adenocarcinoma (EAC) is rising and the only known precursor of this disease is Barrett's esophagus (BE). EAC mortality remains high, prompting strategies to screen individuals with gastroesophageal reflux disease (GERD) symptoms to identify BE and conduct surveillance in order to detect neoplasia at a stage that is amenable to cure. The effectiveness of endoscopic eradication therapy has been improving with reduced harms, yet it is unclear which patients will benefit from this procedure. This chapter reviews the evidence supporting surveillance for BE to reduce mortality from EAC and combines these results with economic analyses to identify the optimal means to manage patients with BE with high-grade dysplasia, low-grade dysplasia, or no dysplasia.

To evaluate how antireflux surgery influences the risk of esophageal cancer in patients with gastroesophageal reflux disease (GERD) and Barrett esophagus. GERD is a major risk factor for esophageal adenocarcinoma, and the United Kingdom has the highest incidence of esophageal adenocarcinoma globally. Hospital Episode Statistics database was used to identify all patients in England aged over 18 years diagnosed with GERD with or without Barrett Esophagus from 2000 to 2012, with antireflux surgery being the exposure investigated. The Clinical Practice Research Datalink (CPRD) was used to provide a sensitivity analysis comparing proton pump inhibitor therapy and antireflux surgery. Hazard ratios (HR) with 95% confidence intervals (CI) were calculated using Cox proportional hazards model with inverse probability weights based on the probability of having surgery to adjust for selection bias and confounding factors. (i) Hospital Episode Statistics analysis; among 838,755 included patients with GERD and 28,372 with Barrett esophagus, 22,231 and 737 underwent antireflux surgery, respectively. In GERD patients, antireflux surgery reduced the risk of esophageal cancer (HR = 0.64; 95% CI 0.52-0.78). In Barrett esophagus patients, the corresponding HR was (HR = 0.47; 95% CI 0.12-1.90).(ii) CPRD analysis; antireflux surgery was associated with decreased point estimates of esophageal adenocarcinoma in patients with GERD (0% vs. 0.2%; P = 0.16) and Barrett esophagus (HR = 0.75; 95% CI 0.21-2.63), but these were not statistically significant. Antireflux surgery may be associated with a reduced risk of esophageal cancer risk, however it remains primarily an operation for symptomatic relief.

While the incidence of esophageal adenocarcinoma (EAC) has risen drastically in Western countries over the last 40 years, a similar trend has not been observed for EAC in China. Here, we analyzed mutational spectrum, copy number alterations, and structural variants from whole-genome sequencing of 10 Chinese EAC tumor samples and their matched normal samples, and compared them to previously reported EAC tumor specimens from Western countries. The mutational burden in Chinese EAC was significantly lower than that found in EAC from Western countries. The hallmark A>C mutational signature observed at high frequency in EAC from Western countries, which has been linked to acid reflux, is completely absent in Chinese samples. Furthermore, none of the Chinese samples showed evidence of chromothripsis and genome doubling that are often found in EAC from Western countries. In summary, Chinese EAC tumor samples had distinct genomic profiles and signatures, suggesting that EAC in Chinese individuals may arise from a different etiological pathway.