Search

Background: It is unclear whether patients of all races and ethnicities with gastroenteropancreatic (GEP) neuroendocrine neoplasm (NEN) have equivalent incidence and cancer-specific survival., Patients and Methods: Using the California Cancer Registry, all patients with GEP-NEN in California's large and diverse population from 1992 to 2019 were identified. Age-adjusted incidence rates (AIRs) and cancer-specific mortality (CSM) risks were compared across racial and ethnic subgroups using structural equation modeling., Results: The non-Hispanic (NH) Black population had the highest rate of diagnosis every year (AIR2019, 7.4 per 100,000; 95% CI, 6.4-8.5). The AIRs across races and ethnicities and primary sites vary, and in 2019 statistically significantly increased for stomach, small intestine, pancreatic, and rectal NEN and for only the NH White population. Risk of mortality was neutral across many races and ethnicities for many primary sites. The only statistically significant disparity was a higher CSM rate for Hispanic patients compared with NH Black patients with small intestine NEN (subdistribution hazard ratio, 1.45; 95% CI, 1.10-1.91; P=.008). Findings suggest a higher CSM among NH Black and NH White patients with rectal NEN. Disparities in who presents with GEP-NEN were revealed across racial and ethnic populations and primary sites. The NH Black population incurred the highest rate overall consistently every year. This is the first study to evaluate cancer-specific survival disparities in all GEP-NEN primary sites across the Asian American/Native Hawaiian/Pacific Islander, Hispanic, NH Black, and NH White racial and ethnic populations. Many clinical and sociodemographic measures associated with risk of mortality differed across race and ethnicities. After careful control of those imbalances, there were few racial and ethnic disparities in risk of CSM., Conclusions: There is room to improve equity in the health care system and close the gap in diagnoses for the NH Black population with all GEP-NEN and in mortality for the Hispanic population with small intestine NEN.

This longitudinal ecological study analyzed racial disparities in mortality trends for stomach cancer (SC) and colorectal cancer (CRC) in Brazil (2000 to 2023) stratified by sex. Data from the National Mortality Information System were analyzed for individuals aged 25 to 80. Self-reported race/skin color followed the Brazilian Institute of Geography and Statistics classification: White (White group) and Black or Brown/multiracial (Black group). Age-standardized mortality rates used the world population as a reference, and Prais-Winsten autoregression calculated trends. SC mortality rates declined for both sexes and racial groups, with a greater reduction in the Annual Percent Change (APC) among Whiteindividuals. Conversely, CRC mortality rates increased, with the Black group showing a higher percentage increase in APC. Despite progress in reducing SC mortality, disparities persist, particularly for CRC, where Black populations experience worse outcomes. Higher SC and CRC mortality rates were observed among White individuals, but the trends highlight the growing burden of CRC in Black populations. These findings emphasize the urgent need to address racial disparities in cancer outcomes, as they remain a critical public health challenge despite advancements in healthcare access and disease control in Brazil.

Background: Various population-based studies have shown Hispanic/Latino ethnicity is a risk factor for worse survival in patients with gastric cancer linked to disparate access to care. We aimed to address whether Hispanic patients treated within safety-net hospital systems continue to experience this survival deficit compared to non-Hispanic patients., Methods: We performed a retrospective cohort study comparing survival between Hispanic and non-Hispanic patients diagnosed with gastric adenocarcinoma between January 1, 2016, and December 31, 2020, within Los Angeles County's safety-net hospital system. Gastric cancer-specific survival was compared between the two cohorts using the Kaplan-Meier estimate and Cox proportional-hazards regression model., Results: In total, 448 patients who received care from five medical centers were included; 348 (77.7%) patients self-identified as Hispanic and 100 (22.3%) as non-Hispanic. Mean follow-up time was 2.0 years (median 0.91 years, IQR, 0.34-2.5 years). Hispanic patients were found to be diagnosed at a younger age (55.6 vs. 60.7 years, P < 0.01), demonstrate higher state area deprivation index (6.4 vs. 5.0, P < 0.01), and present with metastatic disease (59.8% vs. 45%, P = 0.04). After adjusting social and oncologic variables, Hispanic ethnicity remained an independent risk factor for worse survival [HR 1.56, (95% CI, 1.06-2.28); P = 0.02]., Conclusions: Hispanic patients treated within a large, multicenter safety-net hospital system experience worse survival compared to non-Hispanic patients. This suggests ethnic disparities exist within safety-net hospital systems, independent of known clinicopathologic factors., Impact: Improving outcomes for Hispanic patients with gastric cancer requires future efforts aimed at defining and addressing these unidentified barriers to care. See related In the Spotlight, p. 12., (©2024 American Association for Cancer Research.)

Background: Identification of groups at a high risk of gastric cancer could facilitate targeted screening in countries with a low gastric cancer incidence. Our aim was to identify such high-risk groups based on individual-level population data on migration history and socioeconomic status (SES) in the Netherlands., Methods: In this retrospective cohort study, patient data from the Netherlands Cancer Registry were linked to demographic data of Statistics Netherlands in the period 2010 to 2022. Gastric cancer incidence rates in the 14 largest immigrant populations were compared with those born in the Netherlands. Odds ratios (OR) were computed per birthplace and controlled for age, sex, and SES. Additionally, we investigated gastric cancer risk among second-generation immigrants and by SES., Results: Immigrant populations at a significantly higher gastric cancer risk compared with the general population were identified. Specifically, foreign-born first-generation immigrants from Bosnia-Herzegovina (OR, 2.42), Turkey (OR, 2.22), and China (OR, 1.92) showed elevated risk. Whereas low SES increased the odds of developing gastric cancer, first-generation immigrants remained at higher risk even after controlling for SES. Second-generation immigrants did not have a significantly higher risk of developing gastric cancer., Conclusions: Certain first-generation immigrants remain at an elevated risk for gastric cancer despite migration to a low-risk region. Identification of these high-risk groups should be used to facilitate targeted gastric cancer prevention., Impact: Potential benefits of targeted Helicobacter pylori test-and-treat policy in immigrant populations should be explored in clinical and modeling studies. Primary care physicians should be cognizant of high-risk groups, facilitating the early detection of cancer within these populations., (©2024 The Authors; Published by the American Association for Cancer Research.)

Introduction: In aggregate, Asian patients have a higher incidence and mortality from gastric cancer (GC) than Non-Hispanic White (NHW) patients. However, there is a lack of data regarding outcomes among Asian-American subpopulations with GC., Methods: The National Cancer Database was used to identify patients with GC between 2004 and 2020. Asian patients were disaggregated by region, with a further subanalysis of Eastern Asians. Outcomes of interest included the initial localized/regional presentation versus metastatic disease and cancer care measures including undergoing surgical excision or resection for stages I-III, receiving guideline-concordant care, receiving delayed treatment (> 90 days for any treatment type), and overall survival. Outcomes were adjusted for patient/disease characteristics, treatment, and zip-code socioeconomic factors using logistic regression., Results: Among 182,811 patients with GC, 7.2% (n = 13,051) were classified as Asian. More than one-half of the Asian cohort was categorized as East Asian (n = 6,762, 50.1%), with Chinese patients compromising 44.0% (n = 2972) of this subcohort. East Asian patients had greater odds of presenting with nonmetastatic disease (odds ratio [OR] 1.59; P < 0.001), undergoing a curative-intent resection (OR 1.52; P < 0.001), and receiving guideline-concordant care (OR 1.26; P < 0.001) compared to NHW patients. Asians from outside of East, Southeast, and South Asia had increased odds of delayed treatment (OR 1.29, P = 0.024). Asians, in aggregate and by each subpopulation, had a lower mortality risk than NHW patients (P < 0.001)., Conclusions: Asian patients with GC have improved outcomes in aggregate compared to NHW patients, largely driven by the East Asian subpopulation. All Asian subpopulations demonstrated improved survival in comparison with NHW patients., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Overall, gastric adenocarcinoma (GC) incidence rates have declined in recent years, but racial and ethnic disparities persist. Individuals who identify as Hispanic/Spanish/Latino are diagnosed with GC at younger ages and have poorer outcomes than non-Hispanic individuals. However, our understanding of GC biology across racial/ethnic groups remains limited. We assessed tumor genomic patterns by race/ethnicity among 1019 patients with primary GC in the American Association for Cancer Research (AACR) Project GENIE Consortium. Hispanic individuals presented with significantly higher rates of ERBB2/HER2 amplification vs other racial/ethnic groups (Hispanic: 13.9% vs 9.8% non-Hispanic White, 8.1% non-Hispanic Asian, and 11.0% non-Hispanic Black; P < .001, FDR adjusted q < 0.001). Hispanic patients also had higher odds of an ERBB2 amplification vs non-Hispanic Whites in adjusted models (OR = 2.52, 95%CI = 1.20 to 5.33, P = .015). These findings underscore the important role of genomic factors in GC disparities. Ensuring equitable access to genomic profiling and targeted therapies, such as trastuzumab for HER2-overexpressing GC, is a promising avenue to mitigate GC disparities and improve outcomes., (© The Author(s) 2024. Published by Oxford University Press.)

Racial and ethnic disparities in incidence and mortality are well documented for many types of cancer. As a result, there is understandable policy and clinical interest in race- and ethnicity-based clinical screening guidelines to address cancer health disparities. Despite the theoretical benefits, such proposals do not typically address associated ethical considerations. Using the examples of gastric cancer and esophageal adenocarcinoma, which have demonstrated disparities according to race and ethnicity, this article examines relevant ethical arguments in considering screening based on race and ethnicity., Race- and ethnicity-based clinical preventive care services have the potential to improve the balance of harms and benefits of screening. As a result, programs focused on high-risk racial or ethnic groups could offer a practical alternative to screening the general population, in which the screening yield may be too low to demonstrate sufficient effectiveness. However, designing screening according to socially based categorizations such as race or ethnicity is controversial and has the potential for intersectional stigma related to social identity or other structurally mediated environmental factors. Other ethical considerations include miscategorization, unintended negative effects on health disparities, disregard for underlying risk factors, and the psychological costs of being assigned higher risk., Given the ethical considerations, the practical application of race and ethnicity in cancer screening is most relevant in multicultural countries if and only if alternative proxies are not available. Even in those instances, policymakers and clinicians should carefully address the ethical considerations within the historical and cultural context of the intended population. Further research on alternative proxies, such as social determinants of health and culturally based characteristics, could provide more adequate factors for risk stratification., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0377.

Introduction: Current strategies for upper gastrointestinal (UGI) cancer screening primarily target cancer-specific risk, with the strongest focus on esophageal adenocarcinoma (EAC). However, all UGI cancers are amendable to screening and early detection with an upper endoscopic examination. This study assesses and explores incidence-based mortality (IBM) for cumulative UGI cancers, aiming to identify race-based or sex-based disparities., Methods: We used Surveillance, Epidemiology, and End Results Research data to analyze patients diagnosed with EAC, esophageal squamous cell carcinoma, cardia gastric cancer, noncardia gastric cancer, or colorectal adenocarcinoma from 2000 to 2019. Age-adjusted IBM was calculated as a rate per 100,000 population and stratified by sex and race/ethnicity. We also compared UGI cancer IBM with that of colorectal cancer, a cancer with established population-wide endoscopic screening guidelines., Results: Cumulative IBM for UGI cancers was 8.40 (95% confidence interval [CI] 8.34-8.46). The highest cancer-specific IBM rates were for EAC (2.26, 95% CI 2.23-2.29), followed by noncardia gastric cancer (2.07, 95% CI 2.04-2.10), cardia gastric cancer (1.60, 95% CI 1.57-1.62), esophageal squamous cell carcinoma (1.21, 95% CI 1.19-1.23), and miscellaneous UGI cancer (1.27, 95% CI 1.13-1.40). UGI cancer IBM was highest among Black men (16.43, 95% CI 15.97-16.89), American Indian/Alaska Native men (15.23, 95% CI 13.75-16.82), and Hispanic men (13.76, 95% CI 13.42-14.11). These rates are significantly greater than among White men (12.81, 95% CI 12.68-12.95)., Discussion: UGI cancers impose a significantly higher mortality burden on non-White population subgroups that are not currently targeted by any systematic screening approach., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Disparities in gastric cancer (GC) outcomes show a higher disease burden among minorities. We aimed to evaluate the associations between sociodemographic and system-level factors and guideline-concordant treatment among GC patients., Methods: Cohort study with GC patients in the National Cancer Data Base (2006-2018) treated with upfront resection or neoadjuvant therapy (NAT). We used logistic regression to identify associations between deviations from guideline-concordant therapy and patient- and system-level factors, and Cox regression models to assess risk of death., Results: The cohort included 43 597 GC patients treated with endoscopic resection (8.9%), surgery only (47.1%), surgery and adjuvant therapy (20.6%), or NAT followed by surgery (23.5%). A total of 31 470 patients (72.2%) received guideline-concordant therapy. Relative to Non-Hispanic Whites (NHWs), Non-Hispanic Blacks (NHBs) (odds ratio [OR] 1.19, [95% confidence intervals 1.10-1.28]) and Asian/Pacific Islanders (APIs) (OR 1.12 [1.03-1.23]) had an increased risk of deviations from treatment guidelines. Medicare/Medicaid increased the risk of deviations while treatment at high-volume facilities decreased its risk for all races/ethnicities. Deviations from guidelines were associated with an increased risk of death (hazard ratio 1.56 [1.50-1.63]., Conclusions: Racial disparities in the delivery of guideline-concordant therapy among GC patients are affected by several sociodemographic factors at the patient- and system-level., (© 2024 Wiley Periodicals LLC.)

Colonization of specific bacteria in the human mouth was reported to be associated with gastric cancer risk. However, previous studies were limited by retrospective study designs and low taxonomic resolutions. We performed a prospective case-control study nested within three cohorts to investigate the relationship between oral microbiome and gastric cancer risk. Shotgun metagenomic sequencing was employed to characterize the microbiome in prediagnostic buccal samples from 165 cases and 323 matched controls. Associations of overall microbial richness and abundance of microbial taxa, gene families and metabolic pathways with gastric cancer risk were evaluated via conditional logistic regression. Analyses were performed within each cohort, and results were combined by meta-analyses. We found that overall microbial richness was associated with decreased gastric cancer risk, with an odds ratio (OR) per standard deviation (SD) increase in Simpson's reciprocal index of 0.77 (95% confidence interval [CI] = 0.61-0.99). Nine taxa, 38 gene families and six pathways also showed associations with gastric cancer risk at P < .05. Neisseria mucosa and Prevotella pleuritidis were enriched, while Mycoplasma orale and Eubacterium yurii were depleted among cases with ORs and 95% CIs per SD increase in centered log-ratio transformed taxa abundance of 1.31 (1.03-1.67), 1.26 (1.00-1.57), 0.74 (0.59-0.94) and 0.80 (0.65-0.98), respectively. The top two gene families (P = 3.75 × 10 -4 and 3.91 × 10 -4 ) and pathways (P = 1.75 × 10 -3 and 1.53 × 10 -3 ) associated with gastric cancer were related to the decreased risk and are involved in hexitol metabolism. Our study supports the hypothesis that oral microbiota may play a role in gastric cancer etiology., (© 2021 UICC.)

Background and Aims: CDH1 germline variants have been linked to heritability in diffuse gastric (DGC) and lobular breast cancer (LBC). Studies have not yet assessed whether CDH1 is a cancer-susceptibility gene in other cancers. Herein, we mapped the landscape of pathogenic and likely pathogenic (P/LP) germline variants in CDH1 across various cancers and ethnicities., Methods: We evaluated CDH1 germline P/LP variants in 212,944 patients at one CLIA-certified laboratory (Invitae) and described their frequency in 7 cancer types. We screened for CDH1 variant enrichment in each cancer relative to a cancer-free population from The Genome Aggregation Database version 3 (gnomADv3)., Results: CDH1 P/LP variants were identified in 141 patients, most commonly in patients with DGC (27/408, 6.6%) followed by colorectal signet-ring cell cancer (CSRCC; 3/79, 3.8%), gastric cancer (56/2756, 2%), and LBC (22/6809, 0.3%). CDH1 P/LP variants were enriched in specific ethnic populations with breast cancer, gastric cancer, CRC, LBC, DGC, and CSRCC compared to matched ethnicities from gnomADv3., Conclusion: We report for the first time the prevalence of P/LP CDH1 variants across several cancers and show significant enrichment in CDH1 P/LP variants for patients with CSRCC, DGC, and LBC across various ethnicities. Future prospective studies are warranted to validate these findings., (© 2021. The Author(s).)

We previously found allelic deletions on chromosomes 17 in primary gastric cancers (GC) using microsatellite markers for loss of heterozygosity (LOH). OVCA1 lies in one of these regions (17q21.33). The association between single nucleotide polymorphism (SNP) of OVCA1 gene and risk of gastric cancer is not yet clear. In this study, the peripheral blood of 505 gastric cancer patients and 544 healthy controls were genotyped for six SNPs (rs2273981, rs1131600, rs3752963, rs3803806, rs2236375, and rs1051322) of OVCA1, to evaluate the association of these SNPs with the risk of gastric cancer in the Han population in northeast China. The effect of rs2273981 located in the promoter region of OVCA1 on the transcription activity was determined using dual luciferase reporter assay. We found that the association between the AA + AG genotype of rs2273981 and the risk of gastric cancer was significant in smokers (AA + AG vs. GG, OR = 2.47, 95% CI = 1.04 - 5.87, P < 0.05). Stratified analysis of the clinicopathological parameters revealed that rs1131600 AG + GG genotype were significantly associated with increased gastric tumor volume (AG + GG vs. AA, OR = 1.81, 95% CI = 1.00 - 3.29, P < 0.05). The rs2236375 CT + TT genotype was also significantly associated with increased gastric tumor volume (CT + TT vs. CC, OR = 2.65, 95% CI = 1.38 - 5.10, P < 0.05). Additionally, by interacting with the transcription factor AP2A, the GG genotype the rs2273981 increased the transcription activity of OVCA1 compared with AA genotype, thus involved in gastric cancer development., (Copyright © 2022 Elsevier GmbH. All rights reserved.)

Background: There has been a general reduction over the last 20 years in the incidence within Israel of gastric cancer (GC). This has particularly been noted in the Jewish population with a slight increase in the incidence of cancer of the gastroesophageal junction among Jews of Sephardi origin. Given the diversity of individual ethnic subpopulations, the effects of GC incidence in second-generation immigrant Jews, particularly from high prevalence regions (e.g., the former Soviet Union, Iraq, and Iran), awaits determination. There are currently no national data on GC-specific mortality. The most recent available cross-correlated Israeli National Cancer Registry (INCR) and International Association for Cancer Research (IARC) incidence data for GC of the body and antrum in Israel are presented. Some of the challenges associated with GC monitoring in the changing Israeli population are discussed. We propose the establishment of a national GC management committee designed to collect demographic and oncological data in operable cases with the aim of recording and improving GC-specific outcomes. We believe that there is value in the development of a national surgical planning program, which oversees training and accreditation in a dynamic environment that favors the wider use of neoadjuvant therapies, minimally invasive surgery and routine extended (D2) lymphadenectomy. These changes should be supported by assessable enhanced recovery programs.

Introduction: Several US subgroups have increased risk of gastric cancer and gastric intestinal metaplasia (GIM) and may benefit from targeted screening. We evaluated demographic and clinical risk factors for GIM and examined the interaction between race/ethnicity and birthplace on GIM risk., Methods: We identified patients who had undergone esophagogastroduodenoscopy with gastric biopsy from 3/2006-11/2016 using the pathology database at a safety net hospital in Houston, Texas. Cases had GIM on ≥1 gastric biopsy histopathology, whereas controls lacked GIM on any biopsy. We estimated odds ratios and 95% confidence intervals (CI) for associations with GIM risk using logistic regression and developed a risk prediction model of GIM risk. We additionally examined for associations using a composite variable combining race/ethnicity and birthplace., Results: Among 267 cases with GIM and 1,842 controls, older age (vs <40 years: 40-60 years adjusted odds ratios (adjORs) 2.02; 95% CI 1.17-3.29; >60 years adjOR 4.58; 95% CI 2.61-8.03), Black race (vs non-Hispanic White: adjOR 2.17; 95% CI 1.31-3.62), Asian race (adjOR 2.83; 95% CI 1.27-6.29), and current smoking status (adjOR 2.04; 95% CI 1.39-3.00) were independently associated with increased GIM risk. Although non-US-born Hispanics had higher risk of GIM (vs non-Hispanic White: adjOR 2.10; 95% CI 1.28-3.45), we found no elevated risk for US-born Hispanics (adjOR 1.13; 95% CI 0.57-2.23). The risk prediction model had area under the receiver operating characteristic of 0.673 (95% CI 0.636-0.710) for discriminating GIM., Discussion: We found that Hispanics born outside the United States were at increased risk of GIM, whereas Hispanics born in the United States were not, independent of Helicobacter pylori infection. Birthplace may be more informative than race/ethnicity when determining GIM risk among US populations., (Copyright © 2021 by The American College of Gastroenterology.)

Background and Objectives: The clinical presentation of gastric cancer varies between racial and ethnic groups. While historically studied as a monolithic population, the Hispanic ethnicity is comprised of heterogenous groups with considerable biologic, socioeconomic, and cultural variability; therefore, intragroup differences among Hispanic gastric cancer patients may have been overlooked in past research., Methods: We conducted a retrospective review of the National Cancer Database (NCDB) to compare Hispanic patients with gastric adenocarcinoma diagnosed between 2004 and 2015, by NCDB-reported location of patient ancestry., Results: We identified a cohort of 3811 patients. There were higher proportions of females, patients with early disease onset, and stage 4 disease among patients of Mexican and South/Central American ancestry. Additionally, a significantly larger proportion of Mexican (15%) and South/Central American patients (11%) were diagnosed before age 40, in contrast to Cubans (2%), Dominicans (6%), and Puerto Ricans (3%; p < 0.0001). Mexican ancestry was independently associated with an increased rate of all-cause mortality at 5 years (hazard ratio: 1.34; 95% confidence interval: 1.09-1.64)., Conclusions: Significant clinical and epidemiological differences exist among Hispanic gastric cancer patients based on location of ancestry. Future data collection endeavors should strive to capture this granularity inherent to the Hispanic ethnicity., (© 2021 Wiley Periodicals LLC.)

In our study, we aimed to assess the long-term risk of gastric cardia adenocarcinoma (GCA) for patients with different histological cardia lesions to inform future guidelines for GCA screening in China. We conducted a population-based prospective study among 9740 subjects who underwent upper endoscopy screening during 2005 to 2009 and followed until December 2017. Cumulative incidence and mortality rates of GCA were calculated by the baseline histological diagnoses, and the hazard ratios (HRs), overall and by age and sex, were analyzed by Cox proportional hazards models. During a median follow-up of 10 years, we identified 123 new GCA cases (1.26%) and 31 GCA deaths (0.32%). The age-standardized incidence and mortality rates of GCA were 128.71/100 000 and 35.69/100 000 person-years, and cumulative incidence rate in patients with cardia high-grade dysplasia (CHGD), cardia low-grade dysplasia (CLGD) and atrophic carditis (AC)/cardia intestinal metaplasia (CIM) was 25%, 3.05% and 1.58%, respectively. The progression rate and cancer risk of GCA increased monotonically with each step in Correa's cascade. Individuals aged 50 to 69 years had 4.4 times higher GCA incidence than those aged 40 to 49 years. Patients with CLGD had a significantly higher 3-year GCA incidence than the normal group, while patients with AC/CIM had a comparable GCA risk during 3-year follow-up but a higher risk at 5-year intervals. Our results suggested a postponed starting age of 50 years for GCA screening, immediate treatment for patients with CHGD, a 3-year surveillance interval for patients with CLGD, and a lengthened surveillance interval of 5 years for patients with AC/CIM., (© 2021 UICC.)

Gastric cancer (GC) has the third highest rate of cancer incidence and mortality worldwide. First-line immune checkpoint inhibitor (ICI) therapy for advanced GC led to landmark breakthroughs, but which GC patients are most likely to benefit from ICI therapy needs to be investigated in depth and identified via valuable biomarkers. In this letter, we describe superior outcomes in Asian patients than in North American and European patients treated with ICI therapy, and we speculate that positive H. pylori status may be a beneficial prognostic factor for ICI therapy in patients with GC. Many studies have revealed that H. pylori-activated immune responses improve prognosis in patients with GC via increased PD-L1 expression and CD3 + T cells. We propose that H. pylori status should be emphasized in ongoing or forthcoming ICI therapy trials to maximize the benefits of treatment for patients with advanced GC. Further research is required to better understand the mechanisms of inflammation and cancer progression., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Given the growing incidence and aggressive biological behavior of proximal gastric cancer (PGC) as reported, it is important to understand which regional or racial populations are at poor prognosis so that interventions can be treated appropriately. We sought to explore regional treatment differences as well as racial genes influence survival outcomes in China and the US patients with PGC., Methods: PGC patients defined as tumors with the epicenter located in cardia (C16.0) or fundus (C16.1) from 1996 to 2016 were identified from the Surveillance Epidemiology and End Results (SEER) in the United States as well as data from a high-volume National Cancer Center Database in China. Overall survival (OS) curves were plotted for different regional or racial groups, respectively, using the Kaplan-Meier method and compared statistically using the log-rank test. Differentially expressed genes (DEGs) analysis was performed using TCGA database., Results: Finally, the cohort consistent of 40973 PGC patients who enrolled in SEER database (n = 36305) or China National Cancer Center (n = 4668), and divided into 4 racial groups: Chinese (n = 5179), Black (n = 2429), White (n = 31185), and Others (n = 2096). After controlling for confounding variables, racial factors were independently associated with poor survival included Black ethnicity (HR = 1.376, 95% CI: 1.066-1.7760, p = 0.014) and White ethnicity (HR = 1.262, 95% CI: 1.005-1.583, p = 0.045) when compared to Chinese ethnicity in total PGC patients. Even in the same region for only US group, Chinese PGC patients also showed better prognosis., Conclusions: In conclusion, we demonstrated the different survival outcomes of PGC patients in different regions or races from two high-volume database SEER and China National Cancer Center database. These survival differences are likely influenced by a number of factors (e.g., access to screening, quality of gastrectomy, neo/adjuvant therapy, and biological genes itself). More importantly, a better understanding of these disparities could lead to interventions that may help to abolish these disparities., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Introduction: Alaska Native (AN) people experience a high burden of gastric cancer compared with other US Native and non-Native populations. Previous reports have suggested that gastric cancer in AN people occurs at a younger age and is a more aggressive pathologic type. We evaluated all cases of gastric cancer in AN people from 1990 to 2017 and compared the epidemiologic and pathologic characteristics with the gastric cancers that occurred in the same time in the US white (USW) population., Methods: Cancer data were collected by the Alaska Native Tumor Registry and National Cancer Institute's Surveillance, Epidemiology, and End Results Program. Comparisons were performed looking at the age and sex distribution of the affected AN and USW people, as well as the cancer characteristics, including the location, stage, and pathology., Results: The age distribution was significantly different between AN and USW patients (P < 0.001), with a greater proportion of AN people diagnosed younger than 40 years (11% vs 3%, P < 0.0001) and 40-59 years (37% vs 20%, P < 0.0001). In addition, a greater proportion of AN people were diagnosed with distant stage cancer (AN: 48% and USW: 35%, P < 0.0001). The age-adjusted rate of gastric cancer in the AN population was significantly higher than the USW population (20.8 vs 6.7 per 100,000 persons, P < 0.0001). Although there has been a significant decrease in the gastric cancer incidence rate in the USW population, no significant change in incidence was seen in the AN population., Discussion: This study highlights the disproportionate burden of gastric cancer in the AN population. Further work is needed to address and understand this disparity., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Recent findings indicate a shift in the epidemiology of non-cardia gastric cancer in the USA. In particular, an uprising trend in incidence rates among non-Hispanic whites aged < 50 years., Aim: To examine secular trends in the incidence of non-cardia gastric cancer among adults aged < 50 years in the USA by race/ethnicity and stage at diagnosis., Methods: Age-adjusted incidence rates and trends in adults aged < 50 years and ≥ 50 years were calculated using data from all 50 states in the National Program of Cancer Registries and the SEER program. We used joinpoint regression to compute average annual percent change (AAPC) in cancer incidence rates., Results: Overall, we found an increasing trend of non-cardia gastric cancer among non-Hispanic whites aged < 50 years between 2001 and 2014 (AAPC = 1.24, 95% CI 0.49, 1.99). However, among non-Hispanic whites aged < 50 years, the rates of localized disease increased (AAPC = 5.28, 95% CI 3.94, 6.64), whereas the rates of distant stage non-cardia gastric cancer remained unchanged (AAPC = 0.68, 95% CI - 0.63, 2.00). Conversely, we found a significant increase in rates of distant stage non-cardia gastric cancer among Hispanics aged < 50 years (AAPC = 1.78, 95% CI 0.66, 2.91). Non-cardia gastric cancer incidence rates decreased over the study period among non-Hispanic whites and Hispanics aged ≥ 50 years., Conclusion: Given the rapid growth of the young Hispanic population in the USA, preventative strategies for non-cardia gastric cancer cannot neglect this population.

Folate (vitamin B9) is found in some water-soluble foods or as a synthetic form of folic acid and is involved in many essential biochemical processes. Dietary folate is converted into tetrahydrofolate, a vital methyl donor for most methylation reactions, including DNA methylation. 5,10-methylene tetrahydrofolate reductase (MTHFR) is a critical enzyme in the folate metabolism pathway that converts 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, which produces a methyl donor for the remethylation of homocysteine to methionine. MTHFR polymorphisms result in reduced enzyme activity and altered levels of DNA methylation and synthesis. MTHFR polymorphisms have been linked to increased risks of several pathologies, including cancer. Breast cancer, gliomas and gastric cancer are highly heterogeneous and aggressive diseases associated with high mortality rates. The impact of MTHFR polymorphisms on these tumors remains controversial in the literature. This review discusses the relationship between the MTHFR C677T and A1298C polymorphisms and the increased risk of breast cancer, gliomas, and gastric cancer. Additionally, we highlight the relevance of ethnic and dietary aspects of population-based studies and histological stratification of highly heterogeneous tumors. Finally, this review discusses these aspects as potential factors responsible for the controversial literature concerning MTHFR polymorphisms.

Purpose: Gastrointestinal cancers (GICs) account for about a quarter of cancers. Lately, the circulating microRNAs as a non-invasive biomarker for identifying and monitoring diseases have been recognized. Several studies have examined the role of miR-21 in digestive system carcinoma. We conducted a meta-analysis to assess the diagnostic role of miR-21 in GICs. Methods: Seventeen studies involving 1700 individuals were included in this meta-analysis. The pooled sensitivity, specificity, PLR, NLR, DOR, AUC, SROC, and Q* index were calculated based on true-positive, true-negative, false-negative, and false-positive. Moreover, the subgroup analyses have been performed for miR-21 based on sample types (serum/plasma), normalized genes (U6, miR-16, and miR-39), and ethnicity. Results: The pooled sensitivity 0.722 (95% CI: 0.70-0.74), specificity 0.820 (95% CI: 0.801-0.838), PLR 4.375 (95% CI: 3.226-5.933), NLR 0.308 (95% CI: 0.239-0.398), DOR 16.06 (95% CI: 9.732-26.53) as well as AUC 0.86, and Q* index 0.79 represented the high-grade diagnostic precision of miR-21 in identifying GICs (ESCC, GC, CRC, HCC, and PC). Conclusion: This meta-analysis demonstrated that circulating miR-21 levels can be used to monitor the digestive system carcinomas. Therefore, miR-21 can be a useful biomarker of progression and fair diagnosis in GICs patients.

Background: Surgical resection with adequate lymphadenectomy is regarded the only curative option for gastric cancer. Regarding minimally invasive techniques, mainly Asian studies showed comparable oncological and short-term postoperative outcomes. The incidence of gastric cancer is lower in the Western population and patients often present with more advanced stages of disease. Therefore, the reproducibility of these Asian results in the Western population remains to be investigated., Methods: A randomized trial was performed in thirteen hospitals in Europe. Patients with an indication for total gastrectomy who received neoadjuvant chemotherapy were eligible for inclusion and randomized between open total gastrectomy (OTG) or minimally invasive total gastrectomy (MITG). Primary outcome was oncological safety, measured as the number of resected lymph nodes and radicality. Secondary outcomes were postoperative complications, recovery and 1-year survival., Results: Between January 2015 and June 2018, 96 patients were included in this trial. Forty-nine patients were randomized to OTG and 47 to MITG. The mean number of resected lymph nodes was 43.4 ± 17.3 in OTG and 41.7 ± 16.1 in MITG (p = 0.612). Forty-eight patients in the OTG group had a R0 resection and 44 patients in the MITG group (p = 0.617). One-year survival was 90.4% in OTG and 85.5% in MITG (p = 0.701). No significant differences were found regarding postoperative complications and recovery., Conclusion: These findings provide evidence that MITG after neoadjuvant therapy is not inferior regarding oncological quality of resection in comparison to OTG in Western patients with resectable gastric cancer. In addition, no differences in postoperative complications and recovery were seen.

Background: Upper gastrointestinal tract cancers are the leading causes of cancer-related deaths in Northwest China and they share many similarities in terms of histological type, risk factors, and genetic variants. We hypothesized that shared common single-nucleotide polymorphisms (SNPs) in the p53 pathway exist between patients with gastric and esophageal cancer (EC) patients. Materials and Methods: A case-control study to examine genetic variants in the p53 pathway was conducted with subjects from a high-incidence area for upper gastrointestinal cancers of China. Multiple logistic regression analyses were used to estimate the association of genotypes with gastric cancer and EC risks. Median survival was estimated by using the Kaplan-Meier method and compared by using the log-rank test. Results: Compared with the rs1042522 Pro allele, the rs1042522 Arg allele was associated with an increased risk of gastric cancer (1.810×) and an increased risk of EC (2.285×). The rs1042522 Arg allele carriers who also smoked or consumed alcohol had a further increased risk for gastric cancer odds ratios (OR smoking  = 2.422, OR drinking  = 5.152) and EC (OR smoking  = 5.310, OR drinking  = 8.359). No association was found between the rs1042522 genotypes and survival ( p  > 0.05). Conclusion: The p53 rs1042522 arg allele together with tobacco smoking and alcohol drinking, was associated with an increased risk, for gastric cancer and EC, but not the survival among northwestern Chinese patients. These associations warrant confirmatory studies.

Recently, four single nucleotide polymorphisms (rs2585428, rs4809960, rs6022999 and rs6068816) in CYP24A1 gene were extensively studied for their associations with cancer risk. However, these studies included only a few types of cancer, which calls for further investigations. In view of this, we here conducted a case-control study to explore the associations between these four CYP24A1 gene polymorphisms and risk of liver, lung and gastric cancer in a Chinese population. A total of 480 liver cancer patients, 550 lung cancer patients, 460 gastric cancer patients and 800 normal controls were recruited in this study. The genotyping of CYP24A1 gene polymorphisms was applied with Sanger sequencing assay. Single-locus analysis demonstrated that rs6022999 was significantly associated with risk of liver and lung cancer, while rs6068816 was significantly associated with the risk of gastric cancer. Haplotype analysis revealed that haplotype GTAT was associated with an increased risk of liver cancer and a decreased risk of lung cancer, and haplotype ATGC was associated with a decreased risk of lung cancer. The further meta-analysis of rs6068816 and lung cancer risk showed that rs6068816 was not associated with lung cancer risk in Chinese population, which confirmed our present finding. Conclusively, rs6022999 may be a genetic biomarker for liver and lung cancer susceptibility in Chinese population, and rs6068816 may be used to predict gastric cancer risk in Chinese population., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

Introduction: American Indian and Alaska Native (AI/AN) populations have higher gastric cancer rates than the general US population. This study provides a comprehensive overview of incidence rates among AI/AN persons during 2005-2016 compared with non-Hispanic whites (whites)., Methods: Population-based cancer registry data for 2005-2016 were linked with the Indian Health Service patient registration databases to address racial misclassification. Age-adjusted gastric cancer incidence rates were expressed per 100,000 per year. Incidence and trend analyses were restricted to purchased/referred care delivery area counties in 6 geographic regions, comparing gastric cancer incidence rates for AI/AN vs white populations in the United States., Results: Gastric cancer rates were higher in the AI/AN compared with white populations in nearly every US region. Incidence rates for central/distal portions of the stomach were higher in AI/AN individuals compared with whites. Rates of later stage gastric cancer were higher in AI/AN populations overall and in every region except the Pacific Coast and East. Incidence rates decreased significantly over time in both populations. Declining rates in the AI/AN populations were driven by changes in the Pacific Coast and Northern Plains regions., Discussion: AI/AN populations have a disproportionately high incidence of gastric cancer, especially in Alaska. High incidence in the central/distal portions of the stomach among AI/AN populations likely reflects a high prevalence of Helicobacter pylori infection in these populations. These data can be used to develop interventions to reduce risk factors and improve access to health services among AI/AN people at high risk for gastric cancer.

This retrospective study aimed to investigate ethnic disparities in demographic, clinicopathologic, and biological behaviours of gastric cancer (GC) in a high GC incidence area of China. There were 5022 GC patients, including 3987 Han (79.4%) and 987 Hui (14.4%) patients from Northwest China. All patient data were retrieved from 2009 to 2017. Median survival was estimated using the Kaplan-Meier method and compared using the log-rank test. A Cox proportional hazards model was used to assess the impact of covariates. Similarly, low 5-year OS rates were observed in both the Hui and Han groups (23.8% and 24.2% respectively). Hui patients with stage T1 or N0 or with tumours <5 cm had 2.144-fold, 1.426-fold and 1.305-fold increased risks of poor prognosis compared with Han patients with these characteristics respectively (all p < 0.05). Further, Hui patients had 1.265-fold, 1.364-fold and 1.401-fold increased risks of poor prognosis compared with Han patients among those with high expression of Ki67, EGFR and VEGF respectively (all p < 0.05). There are ethnic disparities in the prognosis of GC patients in Northwest China. Understanding the effects of ethnicity on GC will guide reasonable evaluations of prognosis and future interventions to equalise access to high-quality care for GC patients of different ethnicities in China., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Objective: Gastric cancer is the most common gastrointestinal malignancy in China and results from a combination of genetic and environmental factors. The present study was conducted to investigate the relationship between long noncoding RNA (lncRNA) materally expressed gene 3 (MEG3) single nucleotide polymorphisms (SNPs) and the risk of gastric cancer and to construct a genetic-environmental risk assessment model., Methods: A case-control study was conducted to include 474 patients with gastric cancer diagnosed by clinical and pathological examination and 543 healthy physical examination subjects. Blood samples, general demographic data and behavioral lifestyle of the subjects were collected. The TaqMan real-time PCR method was used for testing the genotypes of MEG3 rs7158663 and rs10132552., Results: The A allele at the rs7158663 loci of MEG3 was found to be risk factor for gastric cancer (odds ratio (OR) = 1.41, 95% confidence interval (95% CI) = 1.14-1.74, P=0.002). Yet, no significant association between rs10132552 polymorphisms and gastric cancer was observed. Drinking, tea drinking and preserved food eating were risk factors for gastric cancer (P<0.05). A genetic-environmental risk assessment model was established by using the logistic regression model to include MEG3 rs7158663, drinking, tea drinking, and preserved food eating. With the increase in risk score (RS), the risk of gastric cancer increased substantially (P<0.05). And the area under the receiver operating characteristic (ROC) curve was 0.745, which indicates a high diagnostic value., Conclusions: MEG3 rs7158663 might be associated with the risk of gastric cancer; the diagnostic ability of genetic-environmental risk assessment model for gastric cancer is better., (© 2020 The Author(s).)

Background & Aims: There are racial and ethnic differences in the incidence of gastric adenocarcinoma worldwide and in the US. Based on a decision analysis, screening for noncardia gastric adenocarcinoma might be cost-effective for non-White individuals 50 years or older. However, a lack of precise, contemporary information on gastric adenocarcinoma incidence in specific anatomic sites for this age group has impeded prevention and early detection programs in the US. We aimed to estimate the differences in gastric adenocarcinoma incidence in specific anatomic sites among races and ethnicities in individuals 50 years or older., Methods: We analyzed California Cancer Registry data from 2011 through 2015 to estimate incidences of gastric adenocarcinoma in specific anatomic sites for non-Hispanic White (NHW), non-Hispanic Black, Hispanic, and the 7 largest Asian American populations. We calculated the differential incidence between non-White groups and NHW using incidence rate ratios and 95% confidence intervals (CIs)., Results: Compared with NHW subjects, all non-White groups had significantly higher incidences of noncardia gastric adenocarcinoma; the incidence was highest among Korean American men 50 years and older (70 cases per 100,000). Compared with NHW subjects 50 years and older, the risk of noncardia gastric adenocarcinoma was 1.8-fold (95% CI, 1.37-2.31) to 7.3-fold (95% CI, 5.73-9.19) higher in most non-White groups and 12.0-fold (95% CI, 9.96-14.6) to 14.5-fold (95% CI, 12.5-16.9) higher among Korean American men and women 50 years and older, respectively. Compared with NHW men 50 years and older, all non-White men, except Japanese and Korean American men, had a significantly lower risk of cardia gastric adenocarcinoma., Conclusions: We identified several-fold differences in incidences of gastric adenocarcinoma in specific anatomic sites among racial and ethnic groups, with significant age and sex differences. These findings can be used to develop targeted risk reduction programs for gastric adenocarcinoma., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: The prognosis for gastric carcinoma (GC) remains challenging with less than 35% of patients surviving 5 years. GC survival varies greatly by anatomical site, cardia and non-cardia. However, these important differences have not been thoroughly studied in relation to the increasing diversity in US populations such as Florida. In this study we examined, for the first time, the effect of race-ethnicity on risk of death from GC controlling for potential risk factors separately for cardia and non-cardia GCs., Methods: Data on GCs diagnosed in Florida from 2005-2016 were obtained from the statewide cancer registry. Age-standardized GC-specific 5-year survival was computed by anatomical site and race-ethnicity. In addition, a competing risk analysis was performed to assess prognostic factors and to estimate subdistribution hazard ratios of death from GC., Results: Whites had high proportions of cardia GC (43.9%) compared to all racial/ethnic minorities (10.9%, 19.6%, and 13.8% in Blacks, Hispanics, and Asians, respectively; p < .0001). Among 12,302 cases included, there were 7534 deaths from GC and 1179 from other causes. Age standardized GC-specific 5-year survival was significantly lower for Whites (28.0%) compared to Blacks (31.6%), Hispanics (37.6%), and Asians, (39.6%) and significantly lower for cardia GC (25.0%, 95% CI 23.4-26.6) compared to non-cardia GC (37.0%, 95% CI 35.5-38.4). Multivariable competing risk analysis in patients with non-cardia GC showed that Asians (sHR: 0.64, 95% CI 0.51-0.80), Hispanics (sHR 0.71, 95% CI 0.64-0.78), and Blacks (sHR 0.83, 95% CI 0.75-0.92) all had lower risks of death from GC compared to Whites. In patients with cardia GC, only Hispanics had statistically significant lower risk of death from GC than Whites (sHR 0.84, 95% CI 0.74-0.95, p = 0.005)., Conclusions: The study of racial/ethnic survival disparities in patients with GC in Florida reveals Whites as the most disadvantaged group. Whites are more afflicted by cardia GC, which is associated with higher risk of death than non-cardia GC. However, even within non-cardia GC, Whites had higher risk of death than the other racial-ethnic groups. Commonly assessed survival determinants do not adequately explain these unusual disparities; thus, further investigation is warranted.

Background: The literature on the prognostic relevance of signet-ring cell (SRC) histology in gastric cancer (GC) is controversial which is most likely related to inconsistent SRC classification based on haematoxylin-eosin staining. We hypothesised that mucin stains can consistently identify SRC-GC and predict GC patient outcome., Methods: We performed a comprehensive literature review on mucin stains in SRC-GC and characterised the mucin expression in 851 Caucasian GC and 410 Asian GC using Alcian Blue (AB)-Periodic Acid-Schiff (PAS), MUC2 (intestinal-type mucin), and MUC5AC (gastric-type mucin). The relationship between mucin expression and histological phenotype [poorly cohesive (PC) including proportion of SRCs, non-poorly cohesive (non-PC), or mucinous (MC)], clinicopathological variables, and patient outcome was analysed., Results: Depending on mucin expression and cut-offs, the positivity rates of SRC-GC reported in the literature varied from 6 to 100%. Patients with MUC2 positive SRC-GC or SRC-GC with (gastro)intestinal phenotype had poorest outcome. In our cohort study, PC with ≥ 10% SRCs expressed more frequently MUC2, MUC5AC, and ABPAS (p < 0.001, p = 0.004 and p < 0.001, respectively). Caucasians with AB positive GC or combined ABPAS-MUC2 positive and MUC5AC negative had poorest outcome (all p = 0.002). This association was not seen in Asian patients., Conclusions: This is the first study to suggest that mucin stains do not help to differentiate between SRC-GC and non-SRC-GC. However, mucin stains appear to be able to identify GC patients with different outcome. To our surprise, the relationship between outcome and mucin expression seems to differ between Caucasian and Asian GC patients which warrants further investigations.

Background: Racial/ethnic differences in mortality have not been well studied for either non-cardia gastric cancer (NCGC) or cardia gastric cancer (CGC). The aim of this study was to examine the US mortality rates for these cancer subtypes, as well as esophageal adenocarcinoma (EAC) as a comparator., Methods: We identified 14 164 individuals who died from NCGC, 5235 from CGC, and 13 982 from EAC in the Surveillance, Epidemiology, and End Results database between 2004 and 2016. Age-adjusted incidence-based mortality rates and corresponding annual percent changes (APCs) were calculated. Analyses were stratified by race/ethnicity, age, and stage of disease at diagnosis., Results: The mortality rate in NCGC was two- to threefold higher in blacks, Hispanics, and Asians/Pacific Islanders (PI) than non-Hispanic whites, and was significant across all age groups and stages of disease (P < .01). Mortality in CGC was higher in non-Hispanic whites than blacks and Asians/PI, particularly in individuals in the 50-64 year age group and those with stage IV disease. Mortality in EAC was two- to sixfold higher in non-Hispanic whites than all other groups across all age groups and stages of disease. From 2004 to 2016, mortality rates were stable across all racial/ethnic groups in NCGC and CGC, and in minority groups with EAC, but have been rising in non-Hispanic whites with EAC (APC 3.03, 95% CI 0.17-5.96)., Conclusions: This is the largest study of incidence-based mortality in CGC and NCGC and demonstrates racial/ethnic differences in mortality between these subtypes. Mortality rates for NCGC are highest in minority groups, and have been stable in recent years despite declining incidence. Mortality rates for CGC are marginally higher in middle-aged non-Hispanic whites with advanced disease, though have remained stable. In contrast, mortality in EAC has been rising for non-Hispanic whites, in parallel to incidence. Further studies are needed to refine prevention strategies for high-risk individuals dying from these specific cancer subtypes., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Identifying persons at high risk for gastric cancer is needed for targeted interventions for prevention and control in low-incidence regions. Combining ethnic/cultural factors with conventional gastric cancer risk factors may enhance identification of high-risk persons. Data from a prior case-control study (40 gastric cancer cases and 100 controls) were used. A "conventional model" using risk factors included in the Harvard Cancer Risk Index's gastric cancer module was compared with a "parsimonious model" created from the most predictive variables of the conventional model as well as ethnic/cultural and socioeconomic variables. Model probability cutoffs aimed to identify a cohort with at least 10 times the baseline risk using Bayes' Theorem applied to baseline U.S. gastric cancer incidence. The parsimonious model included age, U.S. generation, race, cultural food at ages 15-18 years, excessive salt, education, alcohol, and family history. This 11-item model enriched the baseline risk by 10-fold, at the 0.5 probability level cutoff, with an estimated sensitivity of 72% [95% confidence interval (CI), 64-80], specificity of 94% (95% CI, 90-97), and ability to identify a subcohort with gastric cancer prevalence of 128.5 per 100,000. The conventional model was only able to reach a risk level of 9.8 times baseline with a corresponding sensitivity of 31% (95% CI, 23-39) and specificity of 97% (95% CI, 94-99). Cultural and ethnic data may add important information to models for identifying U.S. individuals at high risk for gastric cancer, who then could be targeted for interventions to prevent and control gastric cancer. The findings of this pilot study remain to be validated in an external dataset., (©2020 American Association for Cancer Research.)

The dysregulation of Ras/Raf/MEK/ERK pathway governs occurrence and progression of cancers. In previous studies, genome-wide association studies (GWAS) have identified multiple gene loci related to gastric cancer. However, a great many genetic loci have been missed due to multiple statistical comparisons of GWAS. In this study, Multi-marker Analysis of GenoMic Annotation (MAGMA) was applied to analyze genes in Ras/Raf/MEK/ERK pathway and their single nucleotide polymorphisms (SNPs) based on Chinese GWAS including 1625 gastric cancer cases and 2100 controls. The SNP effects on gastric cancer susceptibility were calculated on the basis of a logistic regression model. Expression quantitative trait loci (eQTL) analysis was performed based on the genotype-tissue expression (GTEx) project. We identified that three SNPs in MAP2K1, rs4287513, rs76906202 and rs11631448 were markedly associated with gastric cancer risk (rs4287513: OR = 1.30, 95% CI = 1.10-1.54, P = 1.92 × 10 -3 ; rs76906202: OR = 0.87, 95% CI = 0.79-0.96, P = 3.72 × 10 -3 ; rs11631448: OR = 1.21, 95% CI = 1.05-1.39, P = 6.74 × 10 -3 ). All the loci were eQTLs for MAP2K1 in normal gastric samples. Moreover, the low expression of MAP2K1 was significantly associated with poor survival in gastric cancer patients. Thus, MAP2K1 might represent a key gene related to gastric cancer in Ras/Raf/MEK/ERK pathway, whereas SNPs in MAP2K1 confer gastric cancer susceptibility by having biological effects on the MAP2K1 expression.

Purpose: Premature mortality offers an alternative approach for monitoring the burden of mortality; however, little is known about its measures for stomach cancer. In the present study, we investigated temporal changes in premature mortality because of stomach cancer in the Japanese population from 1980 to 2015., Methods: Mortality data for stomach cancer were obtained from the World Health Organization mortality database. Years of life lost (YLL) was calculated using Japanese life tables. The average lifespan shortened was calculated and defined as the ratio of YLL in relation to the expected lifespan., Results: Over a 35-year time frame, the age-standardized rates adjusted to the World Standard Population for deaths from stomach cancer substantially decreased in both sexes. The results from the average YLL (AYLL) measure showed that lifespan of stomach cancer patients was prolonged by about 3 and 5 years in men and women, respectively. The average lifespan shortened measure showed that stomach cancer led to a loss of 18.5% of lifespan among men and of 21.9% among women in 1980, but these numbers were reduced to 13.6% and 14.5%, respectively, in 2015., Conclusions: Our study demonstrated decreasing trends in premature mortality for stomach cancer in Japan over a 35-year period., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Helicobacter pylori is known as an important determinant of preneoplastic lesions or gastric cancer (GC) risk. The bacterial genotypes may determine the clinical outcomes. However, the evidence for these associations has varied between and within continents, and the actual effect of each gene and corresponding allelic variants are still debatable. In recent years, two new models have been proposed to predict the risk of GC; the phylogeographic origin of H. pylori strains and a disrupted co-evolution between H. pylori and its human host, which potentially explain the geographic differences in the risk of H. pylori-related cancer. However, these models and earlier ones based on putative virulence factors of the bacterium may not fully justify differences in the incidence of GC, reflecting that new theories should be developed and examined. Notably, the new findings also support the role of ancestry-specific germline alteration in contributing to the ethnic/population differences in cancer risk. Moreover the high and low incidence areas of GC have shown differences in transmission ecology, largely affecting the composition of H. pylori populations. As a new hypothesis, it is proposed that any high-risk population may have its own specific risk loci (or variants) as well as new H. pylori strains with national/maybe regional gene pools that should be considered. The latter is seen in the Americas where the rapid evolution of distinct H. pylori subpopulations has been occurred. It is therefore proposed that the deep sequencing of both H. pylori and its human host is simultaneously performed in GC patients and age-sex-matched controls from high-risk areas. The expression and functional activities of the identified new determinants of GC must then be assessed and matched with human and pathogen ancestry, because some of risk loci are ancestry-specific. In addition, potential study-level covariates and moderator variables (eg physical conditions, life styles, gastric microbiome, etc) linked to causal relationships, and their impact, should be recognized and controlled., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Hispanic/Latino patients have a higher incidence of gastric cancer and worse cancer-related outcomes compared with patients of other backgrounds. Whether there is a molecular basis for these disparities is unknown, as very few Hispanic/Latino patients have been included in previous studies. To determine the genomic landscape of gastric cancer in Hispanic/Latino patients, we performed whole-exome sequencing (WES) and RNA sequencing on tumor samples from 57 patients; germline analysis was conducted on 83 patients. The results were compared with data from Asian and White patients published by The Cancer Genome Atlas. Hispanic/Latino patients had a significantly larger proportion of genomically stable subtype tumors compared with Asian and White patients (65% vs. 21% vs. 20%, P < 0.001). Transcriptomic analysis identified molecular signatures that were prognostic. Of the 43 Hispanic/Latino patients with diffuse-type cancer, 7 (16%) had germline variants in CDH1 . Variant carriers were significantly younger than noncarriers (41 vs. 50 years, P < 0.05). In silico algorithms predicted five variants to be deleterious. For two variants that were predicted to be benign, in vitro modeling demonstrated that these mutations conferred increased migratory capability, suggesting pathogenicity. Hispanic/Latino patients with gastric cancer possess unique genomic landscapes, including a high rate of CDH1 germline variants that may partially explain their aggressive clinical phenotypes. Individualized screening, genetic counseling, and treatment protocols based on patient ethnicity and race may be necessary. SIGNIFICANCE: Gastric cancer in Hispanic/Latino patients has unique genomic profiles that may contribute to the aggressive clinical phenotypes seen in these patients., (©2020 American Association for Cancer Research.)

Cancer is still a major health problem in China although numerous efforts have been made for its prevention and control. Findings from this study showed that lung cancer remains the most common type of cancer diagnosed, and was attributed to nearly 30% of all cancer-related deaths. The incidence of the five most common cancers, in China, in 2015, including cancers of the lungs, stomach, colorectum, liver and breast, accounted for almost 60% of all cancers diagnosed. The high cancer burden in China highlights the need for further improvement in health education, professional training and the building up an anti-cancer network for introducing and implementing sustainable actions for cancer control., (© 2020 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd. on behalf of Sun Yat-sen University Cancer Center.)

Background/aim: We aimed to evaluate disparities in presentation and treatment of gastric cancer (GC), including time between diagnosis and treatment, based on race, focusing on Japanese patients within the USA., Patients and Methods: The National Cancer Database was queried for patients diagnosed with GC between 2004-2013. Clinical and treatment variables were summarized by race (White, non-Japanese Asian, Japanese). The association between race and overall survival (OS) was evaluated using the log-rank test., Results: A total of 79,481 patients were included. Japanese patients received surgery the earliest after diagnosis in all stages. Regarding radiotherapy, white patients had the shortest waiting time followed by Asian and Japanese patients. Asian patients had better OS at both 3 and 5 years of follow-up. White patients were associated with the lowest OS., Conclusion: Japanese and Asian GC patients have better OS compared to White patients. Moreover, there were disparities in time to both GC diagnosis and treatment, with Japanese patients being sooner diagnosed and surgically treated, which may ultimately impact patient experience., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Aims: There are limited efforts to address modifiable risk factors for gastric cancer (GC) among racial/ethnic groups at higher GC risk, which may reflect decreased public awareness of risk factors. Our primary aim was to assess baseline awareness of GC risk factors and attitudes/potential barriers for uptake of a GC screening program among high-risk individuals. Methods: Participants attended a linguistically and culturally targeted GC educational program in East Harlem (EH)/Bronx and Chinatown communities in New York City. Demographic information and relevant behavioral/lifestyle habits were collected. Participants' ability to identify GC risk factors and attitudes/barriers surrounding GC screening were assessed before and after the program. Results: Of the 168 included participants, most were female with 77% above age 70. Nearly half of participants in the EH/Bronx programs identified themselves as black and 63% as Hispanic/Latino; 93% of the Chinatown participants identified as Chinese. Among EH/Bronx participants, the majority correctly identified older age, smoking, alcohol, H. pylori , family history, race/ethnicity, excess salt, and preserved foods as risk factors. Among Chinatown participants, the majority correctly identified smoking, alcohol, race/ethnicity, and excess salt, although only 53% and 57.8% correctly identified H. pylori and preserved foods, respectively; the majority incorrectly answered that older age was not a major risk factor. The majority in both groups failed to identify male gender as higher risk and incorrectly identified stress and obesity as major risk factors. Participants were more concerned about the potential findings on GC screening tests than the risks and costs or having to take time off work. Conclusion: Among multiracial/ethnic groups of individuals presumably at higher risk for GC, we identified several gaps in baseline knowledge of both modifiable and non-modifiable GC risk factors. Culturally and linguistically appropriate educational interventions may be a worthwhile adjunctive intervention within the context of a targeted GC screening program.

Recent whole-genome sequencing showed frequent mutations of ARID1A in gastric cancer (GC). In this study of a large independent Central European cohort, we evaluated the expression of ARID1A in whole tissue sections (WTS) of GC testing the following hypotheses: ARID1A shows intratumoral heterogeneity, and ARID1A expression and/or heterogeneity correlates with clinicopathological patient characteristics. ARID1A expression was studied by immunohistochemistry in 450 primary GCs and 143 corresponding lymph node metastases. The expression pattern was correlated with clinicopathological characteristics and patient survival. ARID1A genotype and CpG methylation status were additionally analyzed in 7 GCs with a heterogeneous "black-and-white" expression pattern. ARID1A was expressed heterogeneously in 23 (5.1%) GCs, depicting a black-and-white pattern of negative and positive tumor areas. Complete loss of expression was found in 43 (9.6%) GCs. ARID1A status correlated significantly with tumor type according to Laurén, Epstein-Barr virus status, microsatellite instability, PD-L1 status, and nodal spread. There was no correlation with patient survival. In 4 cases with heterogeneous ARID1A expression, frame shift variants were detected. Summing up, heterogeneous or complete loss of ARID1A expression occurred in 14.7% of GCs and correlated with PD-L1 status, indicating potential for future combined anti-PD-L1/ARID1A therapy. In a subgroup of cases, ARID1A loss was heterogeneous, which suggests that ARID1A mutations might be a later event in gastric carcinogenesis., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To evaluate the effectiveness and benefit of the upper gastrointestinal cancer screening in Yangzhong city, Jiangsu province, from 2009 to 2015. Methods: From 2009 to 2015, 31 natural villages with high-incidence of upper gastrointestinal cancer were selected from Baqiao town, Youfang town and Xinglong sub-district in Yangzhong city. 13 776 residents aged 40 to 69 years old were recruited and screened for upper gastrointestinal cancer by using endoscopic examination and pathological diagnosis. Two economic evaluation methods, cost-effectiveness analysis and cost-benefit analysis, were performed to evaluate the current screening schemes. Results: The mean age of all respondents were (53.60±8.14) years old and the males accounted for 43.64% (6 012). A total of 502 cases of upper gastrointestinal tract lesions were detected, including 100 cases of cancer (62 cases of esophagus, gastric/cardiac early stage cancer, 38 cases of advanced stage cancer), 38 cases of severe esophageal hyperplasia/carcinoma in situ, and 15 cases of high-grade intraepithelial neoplasia in stomach/cardia, the detection rate was 0.73%, 0.28% and 0.11%, respectively; the early diagnosis rate was 75.16% (115/153). The cost of a precancerous lesion, a case diagnosed at the early stage and a positive case identified through the upper gastrointestinal cancer screening in Yangzhong City was 10 037.17, 30 460.64 and 22 895.25 RMB, respectively. The early detection cost index from 2009 to 2015 was 0.52, 0.56, 0.48, 0.48, 0.21, 0.30, and 0.26, respectively. The effectiveness-cost ratio from 2009 to 2015 was 3.41, 2.77, 2.66, 2.58, 4.99, 3.12, and 3.48, respectively. Conclusions: The project of early diagnosis and treatment of upper gastrointestinal tract cancer in Yangzhong city has achieved good results and benefits.

The screening, early diagnosis and early treatment project of the upper gastrointestinal cancer had achieved good results since its launch. However, from a national perspective, the endoscopic screening of upper gastrointestinal cancer was still not optimistic, such as the poor rate of the early diagnosis, the low rate of 5-year survival in rural areas, and the disparity of the standardized screening and diagnosis in different areas. Therefore, the situation of upper gastrointestinal cancer prevention and treatment is still severe. Under the guidance of the "Healthy China 2030" plan, based on the international experience and domestic actual circumstance, it is suggested that the screening of high-risk population in high-risk areas should be changed into the opportunistic screening in primary medical institutions. The opportunistic screening could expand the coverage of the screening, early diagnosis and early treatment project of the upper gastrointestinal cancer, and increase the early diagnosis rate in rural areas and primary medical institutions, which could improve the 5-year survival rate of patients with the upper gastrointestinal cancer, and then achieve the sustainable development of the cancer prevention and treatment in China.

Background/aims: In the ABC classification system, group A consists of seronegative subjects without gastric corpus atrophy. This study aimed to determine the prevalence and characteristics of pseudo group A subjects., Methods: Group A subjects were identified among consecutive Korean adults who underwent a serum anti- Helicobacter pylori immunoglobulin G (IgG) test and pepsinogen (PG) assay on the day of endoscopy. Past infection was defined as the presence of either eradication history or endoscopic findings suggesting past infection (i.e., gastric xanthoma, metaplastic gastritis, or advanced atrophy >closed-type 1)., Results: Among 2,620 group A subjects, 448 (17.1%) had eradication history, and 133 (5.1%) showed endoscopic findings suggesting past infection. Older age (odds ratio [OR], 1.148; 95% confidence interval [CI], 1.067 to 1.236) and earlier year of birth (OR, 1.086; 95% CI, 1.009 to 1.168) were independent risk factors for classification into pseudo group A, with cutoff points at 50.5 years and birth year of 1959.5, respectively. Positive H. pylori test findings were found in 22 subjects (3.1%) among the 715 subjects who underwent the urea breath test or Giemsa staining on the same day. Current infection was positively correlated with PG I and PG II levels (p<0.001) but not with age, anti- H. pylori IgG titer, or classification into pseudo group A., Conclusions: Among the group A subjects, 22.2% had past infection. The risk was higher in subjects older than 50 years, especially those born before 1960. Furthermore, current infection was found in 3.1% of the subjects and was correlated with increased gastric secretory ability.

Previous studies have identified the prostate stem cell antigen ( PSCA ) gene rs2294008 C > T and rs2976392 G > A polymorphisms to be associated with the risk of gastric cancer, the results of which are inconsistent. The present study aimed to evaluate the association between the two polymorphisms and the gastric cancer risk in the Chinese population. A hospital-based case-control study was conducted on 549 cases and 592 healthy controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were applied to evaluate the association of the two polymorphisms on the gastric cancer risk. We found that both rs2294008 (CT vs. CC, OR = 1.55, 95% CI = 1.20-1.99, P <0.001 and CT+TT vs. CC, OR = 1.38, 95% CI = 1.09-1.74, P =0.008) and rs2976392 (GA vs. GG, OR = 1.61, 95% CI = 1.25-2.07, P <0.001 and GA+AA vs. GG, OR = 1.52, 95% CI = 1.20-1.92, P <0.001) were associated with an increased gastric cancer. In the combined analysis of the two polymorphisms, subjects with more than one risk genotype have a significantly increased risk of gastric cancer (OR = 1.38, 95% CI = 1.09-1.75, P =0.008) in comparison with those without any risk genotypes. In conclusion, our findings verified that the PSCA gene rs2294008 and rs2976392 polymorphisms were both significantly associated with an increased risk of gastric cancer in the Chinese population. Well-designed functional studies are to be warranted to confirm these findings., (© 2019 The Author(s).)

Background and Objectives: Conflicting evidence indicates that both race and geographic setting may influence the management of malignancies such as gastric adenocarcinoma (GAC)., Methods: We designed a retrospective cohort study utilizing data from the Surveillance, Epidemiology, and End Results program to identify patients with resectable GAC (N = 15 991). Exposures of interest were race and geographic region of diagnosis (West [WE], Midwest [MW], South [SO], or Northeast [NE]). Endpoints included: (1) recommendation against surgery and (2) gastric adenocarcinoma-specific survival (GACSS). Multivariable logistic and Cox regression models were used to identify pertinent associations., Results: A total of 15 991 patients were included (2007-2015). In adjusted analysis, African American individuals more frequently received a recommendation against surgical resection than White (adjusted odds ratio [aOR] = 0.86; 95% confidence interval [CI], 0.76-0.98), Asian American (aOR = 0.55; 95% CI, 0.46-0.65), and American Indian (aOR = 0.50; 95% CI, 0.31-0.82) individuals. In addition to race-based discrepancies, there was a significant association between geography and management: individuals diagnosed with GAC in the SO were more likely to receive a recommendation against surgery (odds ratio = 1.35; 95% CI, 1.23-1.49) and exhibited poorer GACSS as compared with those in the WE, MW, or NE regions., Conclusions: Race and geographic region of diagnosis affect treatment recommendations and GACSS among individuals with resectable tumors. African Americans with resectable cancers are more likely to receive a recommendation against surgery than individuals of other racial groups., (© 2019 Wiley Periodicals, Inc.)

Background: Gastric cancer is an important cause of death among racial/ethnic minorities in the U.S. The objective of this study was to investigate racial disparities in survival among gastric cancer patients within demographic and disease subgroups., Methods: Patients diagnosed with invasive epithelial gastric cancer between 2006 and 2015 were identified from the California Cancer Registry. Cox proportional hazards regression was used to identify factors associated with survival among non-Hispanic whites (NHWs, n = 7,475), non-Hispanic blacks (NHBs, n = 1,246), Hispanics (n = 6,274), and Asians/Pacific Islanders (APIs, n = 4,204). Survival was compared across race/ethnicity within subgroups of demographic and disease factors. Five-year relative survival was also calculated within subgroups., Results: There were notable differences in patient characteristics by race/ethnicity, but predictors of survival were similar for each group. Overall, APIs (HR = 0.83, 95% CI: 0.79, 0.88, p < 0.0001) and Hispanics (HR = 0.94, 95% CI: 0.90, 0.99, p = 0.0104) had better survival than NHWs, but NHBs and NHWs did not have different prognosis (HR = 1.06, 95% CI: 0.98, 1.15, p = 0.2237). The survival advantage of APIs persisted in nearly every demographic and disease subgroup, but Hispanics and NHBs had similar survival as NHWs in most groups. Race was not a significant predictor of survival among those with public or no insurance and patients with cardia tumors., Conclusions: There are some differences in survival by race/ethnicity, but race/ethnicity alone cannot explain disparate outcomes in gastric cancer. Future studies, particularly ones that investigate the role of population-specific etiological factors and molecular tumor profiles, are needed to further understand factors associated with survival.

Background and Objectives: Gastric cancer in the Hispanic population commonly presents with poor clinical features. Characteristics of this vulnerable population and optimal therapy for these patients have not been clearly defined., Methods: Using the National Cancer Database (2004-2014), we analyzed patient demographics, clinical factors, treatment-related factors, and outcomes for Hispanic and non-Hispanic patients with gastric adenocarcinoma in the United States., Results: A total of 129 666 patients were included in this analysis. Hispanics were younger, more often female, had larger tumors, and were more likely to present with metastatic disease (all P < 0.001). Hispanics were more likely to undergo staging laparoscopy (5.6% vs 4.9%; P = 0.037), gastrectomy (63.5% vs 56.9%; P < 0.001), and ≥ 15 lymph nodes examined (56.1% vs 50.5%; P < 0.001). Hispanics were less likely to have negative margins (91.2% vs 92.8%; P = 0.004). Hispanics with stage II/III disease were less likely to receive neoadjuvant therapy (31.7% vs 38.7%; P < 0.001), but more likely to receive multimodal therapy (48.9% vs 46.1%; P = 0.01). Predictors for improved overall survival in Hispanics included multimodal therapy, negative margins, and treatment at an academic center., Conclusions: Efforts to optimize treatment of this distinct and growing population of gastric cancer patients should focus on earlier diagnosis, referral to academic centers, and high-quality surgery., (© 2019 Wiley Periodicals, Inc.)