Etiology Of Gastric Cancer Research Articles

Gastric Cancer Etiology and Management in Asia and the West

Regional variation in treatment paradigms for gastric adenocarcinoma has attracted a great deal of interest. Between Asia and the West, major differences have been identified in tumor biology, implementation of screening programs, extent of surgical lymphadenectomy, and routine use of neoadjuvant versus adjuvant treatment strategies. Minimally invasive techniques, including both laparoscopic and robotic platforms, have been studied in both regions, with attention to safety, feasibility, and long-term oncologic outcomes. The purpose of this review is to discuss advances in the understanding of the etiology and underlying biology of gastric cancer, as well as the current state of management, focusing on the differences between Asia and the West.

Alcohol consumption and risk of gastric cardia adenocarcinoma and gastric noncardia adenocarcinoma: A 16‐year prospective analysis from the NIH‐AARP diet and health cohort

The role of alcoholic beverages in the etiology of gastric cancer is unclear. Recent summaries showed a positive association between higher alcohol intake and gastric cancer risk, but the magnitude of association is small, there is moderate heterogeneity among studies, and most cases were from Asian populations. We prospectively investigated the associations of alcohol consumption with gastric cardia adenocarcinoma (GCA) and gastric noncardia adenocarcinoma (GNCA) in 490,605 adults, aged 50-71 years at baseline who participated in the NIH-AARP diet and health study. Alcohol consumption in the past year was assessed at baseline by questionnaire and defined as total grams of ethanol intake per day or as a categorical variable: nondrinker, up to or including one drink per day, one to three drinks per day and greater than three drinks per day. We used multivariable-adjusted Cox proportional hazards regression to calculate the hazard ratios (HR) and 95% confidence intervals (CI) for associations between alcohol intake and risk of gastric adenocarcinomas. Through 2011, 662 incident cases of GCA and 713 of GNCA occurred. We found no association between higher alcohol consumption and GCA or GNCA, when examined as total alcoholic beverage intake or individual beverage types of beer, wine and liquor. Furthermore, we observed no association by stratum of sex, ethnic group, educational level or smoking status. We did, however, observe lower risk of GNCA among participants who drank up to one drink per day (HR = 0.81, 95% CI: 0.67-0.97) compared to nondrinkers. In conclusion, alcohol consumption was not associated with increased risk of GCA or GNCA in this large U.S. cohort.

The Association Between Index of Nutritional Quality (INQ) and Gastric Cancer and Evaluation of Nutrient Intakes of Gastric Cancer Patients: A Case-Control Study

Background: Gastric cancer (GC) is the fourth major malignancy and the second leading cause of cancer-related deaths worldwide. Northern and northwestern areas of Iran are among the high risk areas for GC. Studies have shown that dietary components are implicated in the etiology of GC. The index of nutritional quality (INQ) is a method of quantitative and qualitative analysis of single foods, meals, and diets. We aimed to assess the association of INQ with GC, and to evaluate the nutrient intake of GC patients. Methods: The present case-control study included 82 cases and 95 healthy controls attending specialized centers in Tabriz, Iran, from December 2014 to May 2016. INQ scores were computed based on dietary intake assessed using a validated 168-item food frequency questionnaire (FFQ). Logistic regression models were used to estimate multivariable ORs adjusted age, gender, Body Mass Index (BMI), smoking, residency, education, and regular physical activity. Results: After controlling for several covariates, inverse associations were observed between GC risk and INQs of vitamins A, B6, and D (ORvitA = 0.25 (0.06 - 0.98); ORvitB6 = 0.10 (0.04 - 0.28); and ORvitD = 0.14 (0.02 - 0.84)). Cases had higher intake of total fat, saturated fatty acids, beef, lamb meat, salt, and paprika compared to controls. On the other hand, controls had higher intake of vitamin A, vitamin, vitamin B6, copper, poultry, low fat milk, tea, coffee, turmeric, and saffron compared to cases. Conclusions: Subjects who follow a more healthy and nutrient-rich diet, especially in terms of vitamins A, B6, and D, are at lower risk of having GC, compared to those who consume a more unhealthy, nutrient-poor diet.

Validation of a Dietary Inflammatory Index (DII) and Association with Risk of Gastric Cancer: a Case-Control Study

Background:Gastric cancer (GC) is the fifth most common malignancy and the second leading cause of cancer-related deaths worldwide. Studies have shown that dietary components and inflammation are implicated in the etiology of GC.Methods:We examined the ability of a dietary inflammatory index (DII) to predict the odds of GC in a case-control study conducted from December 2014 to May 2016. The subjects were 82 cases and 95 controls who attended specialized centers in Tabriz, Iran. DII scores were computed from a validated 168-item food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) adjusted for age, sex, body mass index, education, smoking, alcohol, H.pylori infection, physical activity, aspirin/NSAID use and total caloric intake.Results:In the fully adjusted model, subjects with a DII score >-1.77 had nearly 3.5 times higher odds of having GC compared with subjects with DII≤-1.77, (ORDII>-1.77≤-1.77=3.39; 95%CI=1.59, 7.22). Also, for every one-unit increase in DII, there was a corresponding increase in hs-C-reactive protein, tumor necrosis factor-alpha, interleukin (IL)-6 and IL-1b: β=0.09, 0.16, 0.16 and 0.10, respectively; and a corresponding decrease in IL-10: β=-0.11.Conclusion:Subjects who consumed a more pro-inflammatory diet were at increased odds of GC compared to those who consumed a more anti-inflammatory diet.

LINC00052 Promotes Gastric Cancer Cell Proliferation and Metastasis via Activating the Wnt/β-Catenin Signaling Pathway.

Gastric cancer (GC) is one of the most common malignant tumors of the digestive system. The etiology of GC is complex, and much more attention should be paid to genetic factors. In this study, we explored the role and function of LINC00052 in GC. We applied qRT-PCR and Northern blot to detect the expression of LINC00052 and found it was highly expressed during GC. We also investigated the effects of LINC00052 on tumor prognosis and progression and found that LINC00052 indicated poor prognosis and tumor progression. By performing MTT, colony formation, and Transwell assays, we found that LINC00052 promoted MGC-803 cell proliferation and metastasis. Pull-down and RIP assays showed that LINC00052 could interact with β-catenin and methyltransferase SMYD2, and immunoprecipitation detection showed that LINC00052 promoted β-catenin methylation to maintain its stability, so as to activate the Wnt/β-catenin pathway. Furthermore, XAV939 (inhibitor of β-catenin) was used to treat MGC-803 cells, and we found that LINC00052 promoted proliferation and metastasis, possibly by activation of the Wnt/β-catenin pathway. In conclusion, our research demonstrated a carcinogenic role for LINC000052 in GC, which may represent a new approach for the prevention and therapy of this cancer.

Associations between mutations of the cell cycle checkpoint kinase 2 gene and gastric carcinogenesis.

Gastric cancer is the most common malignant tumor of the digestive system. The etiology of gastric cancer is complex, and susceptibility at the genetic level remains to be fully elucidated in genetic investigations. In the present study, mutations of the cell cycle checkpoint kinase 2 (CHEK2) gene and its association with gastric cancer were examined. Reverse transcription‑quantitative polymerase chain reaction technology was used to detect the expression of CHEK2 and it was found that the expression of CHEK2 was low in gastric cancer. Using sequencing analysis, it was found that the low expression level of CHEK2 was associated with expression of its mutation. The present study also established a CHEK2‑overexpressing mutant and confirmed that CHEK2 promoted gastric cancer cell proliferation. Overexpression of the CHEK2 mutation was confirmed to promote cancer cell migration and invasion. Furthermore, western blot analysis results revealed that overexpression of the CHEK2 mutation downregulated E‑cadherin and upregulated vimentin expression, indicating the mechanism underlying the altered biological behavior. These results suggested that there was a correlation between mutation of the CHEK2 gene and gastric cancer, and provided an experimental basis for antitumor drug investigation and development according to its mutation target.

Abstract LB-254: Thymidylate synthase gene polymorphisms is negatively associated with gastric cancer survival

Abstract Background: Gastric cancer (GC) is a major public health problem in China and its carcinogenesis has not been fully understood. It was found that genetic variation played an important role in the etiology. Thymidylate synthase (TYMS) is a critical target for cancer chemo-therapy, which functions in DNA replication, synthesis and repair. However, the results of the relationship between TYMS and cancer is unclear. To find the genomic susceptibility in TYMS, bio-markers are necessary for preventing and understanding the etiology of gastric cancer. Objectives: The research explores the relationship between TYMS and survival time of 876 Chinese gastric cancer patients. Methods: A retrospective cohort of 876 surgically resected gastric cancer patients with clinicopathologic and follow up information were collected. The genotypes of SNPs were examined by SNaPshot method. The median survival time (MST) for each categorical variable and survival curve were estimated by Kaplan-Meier method. The overall survival was analyzed by univariate and multivariate Cox proportional hazard model. Results: TYMS was significantly associated with survival time. The study found eight samples (1.0%) with the novel allele (4R). In univariate analysis, the group of including 4R allele had lowest survival condition (P value = 0.006). The hazard ratio of individual with 4R allele was 2.48 (95% CI: 1.10-5.58) after controlling age, gender, smoking, drinking and TNM stage. Conclusion: Our study found a novel allele (4R) in TYMS in gastric cancer patients. Key words: Gastric cancer; TYMS; overall survival Citation Format: Jinfei Chen, Maggie Haitian Wang, Benny Chung-Ying Zee. Thymidylate synthase gene polymorphisms is negatively associated with gastric cancer survival [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-254. doi:10.1158/1538-7445.AM2017-LB-254

Genetically predicted high body mass index is associated with increased gastric cancer risk.

Epidemiological studies have linked body mass index (BMI) with risk of gastrointestinal cancers. However, for gastric cancer, the relationship is more controversial. In particular, it is unclear whether the observed association is due to confounding or bias inherent in conventional observational studies. To investigate whether BMI is causally associated with gastric cancer risk, we applied Mendelian randomization using individual-level data from 2631 gastric cancer cases and 4373 cancer-free controls. We derived a weighted genetic risk score (wGRS) using 37 BMI-associated genetic variants as an instrumental variable. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between genetically predicted BMI and gastric cancer risk. We observed that higher genetically determined BMI was associated with increased gastric cancer risk (per standard deviation (SD) increase in the wGRS: OR=1.07, 95% CI: 1.02-1.13, P=4.94 × 10-3). Compared with individuals in the bottom tertile of the BMI wGRS, those in the top tertile had 1.14-fold (95% CI: 1.01-1.29) increased risk of developing gastric cancer. Sensitivity analyses using alternative causal inference measures demonstrated consistent association. Our study indicated that genetically high BMI was associated with increased gastric cancer risk, suggesting that high BMI may have a causal role in the etiology of gastric cancer.

Abdominal obesity and gastroesophageal cancer risk: systematic review and meta-analysis of prospective studies.

To systematically and quantitatively review the relation of abdominal obesity, as measured by waist circumference (WC) and waist to hip ratio (WHR), to total gastroesophageal cancer, gastric cancer (GC), and esophageal cancer. PubMed and Web of Science databases were searched for studies assessing the association between abdominal obesity and gastroesophageal cancer (GC and/or esophageal cancer) up to August 2016. A random-effect model was used to calculate the summary relative risks (RRs) and 95% confidence intervals (CIs). Seven prospective cohort studies – one publication included two separate cohorts – from six publications were included in the final analysis. A total of 2130 gastroesophageal cancer cases diagnosed amongst 913182 participants. Higher WC and WHR were significantly associated with increased risk of total gastroesophageal cancer (WC: RR 1.68, 95% CI: 1.38, 2.04; WHR: RR 1.49, 95% CI: 1.19, 1.88), GC (WC: RR 1.48, 95% CI: 1.24, 1.78; WHR: 1.33, 95% CI: 1.04, 1.70), and esophageal cancer (WC: RR 2.06, 95% CI: 1.30, 3.24; WHR: RR 1.99, 95% CI: 1.05, 3.75).Findings from our subgroup analyses showed non-significant positive associations between gastric non-cardia adenocarcinoma (GNCA) and both measures of abdominal adiposity, while gastric cardia adenocarcinoma (GCA) was positively associated with WC but not with WHR. On analysis restricted to studies that adjusted for body mass index (BMI), WC was positively associated with GC and esophageal cancer, whereas WHR was positively associated with risk of GC only. Although limited, the findings from our meta-analysis suggest the potential role of abdominal obesity in the etiology of gastric and esophageal cancers.

Protein signature characterizing Helicobacter pylori strains of patients with autoimmune atrophic gastritis, duodenal ulcer and gastric cancer

BackgroundHelicobacter pylori (H. pylori) represents a key factor in the etiology of autoimmune atrophic gastritis (AAG), duodenal ulcer (DU) and gastric cancer (GC). The aim of this study was to characterize the differential protein expression of H. pylori isolated from gastric biopsies of patients affected by either AAG, DU or GC.MethodsThe H. pylori strains were isolated from endoscopic biopsies from the stomach of patients with gastric disease. Protein profiles of H. pylori were compared by two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with mass spectrometry (MS) for the identification of significantly different spots (Student t-test, p < 0.05).ResultsA total of 47 differentially expressed spots were found between H. pylori isolated from patients with either DU or AAG diseases and those isolated from patients with GC (Anova < 0.05, log fold change >1.5). These spots corresponded to 35 unique proteins. The identity of 7 protein spots was validated after one-dimensional electrophoresis and MS/MS analyses of excised gel portions. In H. pylori isolated from DU-patients a significant increase in proteins with antioxidant activity emerged (AroQ, AspA, FldA, Icd, OorA and ScoB), together with a higher content of proteins counteracting the high acid environment (KatA and NapA). In H. pylori isolated from AAG-patients proteins neutralizing hydrogen concentrations through organic substance metabolic processes decreased (GroL, TrxB and Tuf). In addition, a reduction of bacterial motility (FlhA) was found to be associated with AAG-H. pylori isolates. In GC-H. pylori strains it was found an increase in nucleic acid-binding proteins (e.g. DnaG, Tuf, RpoA, RplU) which may be involved in a higher demand of DNA- and protein-related processes.ConclusionOur data suggest the presence of specific protein signatures discriminating among H. pylori isolated from either AAG, DU or GC. Changes in protein expression profiles evaluated by DIGE succeeded in deciphering part of the molecular scenarios associated with the different H. pylori-related gastric diseases.

The histone demethylase lysine-specific demethylase-1–mediated epigenetic silence of KLF2 contributes to gastric cancer cell proliferation, migration, and invasion

Gastric cancer is one of the most common malignancies and leading causes of cancer-related death worldwide. An increasing number of evidence has revealed that gastric tumorigenesis is a multistage pathological state, and epigenetic alterations are considered to play critical roles in the etiology of gastric cancer. Lysine-specific demethylase-1, a histone demethylase, has been linked to malignancy in several human cancers and considered to epigenetically regulate many tumor suppressor genes during tumorigenesis and cancer progression. However, its role and underlying targets in gastric cancer are still unclear. In this study, we detected the lysine-specific demethylase-1 expression level in gastric cancer tissues and cell lines and investigated the function and mechanism of lysine-specific demethylase-1 in the gastric cancer. The in vitro analysis shows that knockdown of lysine-specific demethylase-1 significantly inhibits gastric cancer cell proliferation, migration, and invasion and induces cell cycle G1 phase arrest and cell apoptosis. In vivo assays determine that lysine-specific demethylase-1 downregulation represses gastric cancer cell tumorigenesis. Mechanistic investigation reveals that tumor suppressor KLF2 is a key downstream target of lysine-specific demethylase-1 in gastric cancer. These findings indicate that lysine-specific demethylase-1 is an important oncogene in gastric cancer, and lysine-specific demethylase-1-mediated epigenetic repression of KLF2 plays a critical role in gastric cancer development and progression, which supports lysine-specific demethylase-1 as a potential therapeutic target in this disease.

Transcriptomic analysis of gene expression profiles of stomach carcinoma reveal abnormal expression of mitotic components

AimsIn order to explore the etiology of gastric cancer on global gene expression level, we developed advanced bioinformatic analysis to investigate the variations of global gene expression and the interactions among them. Main methodsWe downloaded the dataset GSE63288 from Gene Expression Omnibus (GEO) database which included 22 human gastric cancer and 22 healthy control samples. We identified the differential expression genes, and explored the Gene ontology (GO) and pathways of the differentially expressed genes. Furthermore, integrative interaction network and co-expression network were employed to identify the key genes which may contribute to gastric cancer progression. Key findingsThe results indicated that 5 kinases including BUB1, TTK protein kinase, Citron Rho-interacting kinase (CIT), ZAK and NEK2 were upregulated in gastric cancer. Interestingly, BUB1, TTK, CIT and NEK2 have shown high expression similarities and bound with each other, and participated in multiple phases of mitosis. Moreover, a subnet of co-expression genes e.g. KIF14, PRC1, CENPF and CENPI was also involved in mitosis which was functionally coupled with the kinases above. By validation assays, the results indicated that CIT, PRC1, TTK and KIF14 were significantly upregulated in gastric cancer. SignificanceThese evidences have suggested that aberrant expression of these genes may drive gastric cancer including progression, invasion and metastasis. Although the causal relationships between gastric cancer and the genes are still lacking, it was reasonable to take them as biomarkers for diagnosis of gastric cancer.

Inducible Nitric Oxide Synthase in the Carcinogenesis of Gastrointestinal Cancers.

Gastrointestinal (GI) cancer taken together constitutes one of the most common cancers worldwide with a broad range of etiological mechanisms. In this review, we have examined the impact of nitric oxide (NO) on the etiology of colon, colorectal, gastric, esophageal, and liver cancers. Recent Advances: Despite differences in etiology, initiation, and progression, chronic inflammation has been shown to be a common element within these cancers showing interactions of numerous pathways. NO generated at the inflammatory site contributes to the initiation and progression of disease. The amount of NO generated, time, and site vary and are an important determinant of the biological effects initiated. Among the nitric oxide synthase enzymes, the inducible isoform has the most diverse range, participating in numerous carcinogenic processes. There is emerging evidence showing that inducible nitric oxide synthase (NOS2) plays a central role in the process of tumor initiation and/or development. Redox inflammation through NOS2 and cyclooxygenase-2 participates in driving the mechanisms of initiation and progression in GI cancers. Understanding the underlying mechanism involved in NOS2 activation can provide new insights into important prevention and treatment strategies. Antioxid. Redox Signal. 26, 1059-1077.

Menstrual and Reproductive Factors and Risk of Gastric and Colorectal Cancer in Spain.

BackgroundSex hormones play a role in gastric cancer and colorectal cancer etiology, however, epidemiological evidence is inconsistent. This study examines the influence of menstrual and reproductive factors over the risk of both tumors.MethodsIn this case-control study 128 women with gastric cancer and 1293 controls, as well as 562 female and colorectal cancer cases and 1605 controls were recruited in 9 and 11 Spanish provinces, respectively. Population controls were frequency matched to cases by age and province. Demographic and reproductive data were directly surveyed by trained staff. The association with gastric, colon and rectal cancer was assessed using logistic and multinomial mixed regression models.ResultsOur results show an inverse association of age at first birth with gastric cancer risk (five-year trend: OR = 0.69; p-value = 0.006). Ever users of hormonal contraception presented a decreased risk of gastric (OR = 0.42; 95%CI = 0.26–0.69), colon (OR = 0.64; 95%CI = 0.48–0.86) and rectal cancer (OR = 0.61; 95%CI = 0.43–0.88). Postmenopausal women who used hormone replacement therapy showed a decreased risk of colon and rectal tumors. A significant interaction of educational level with parity and months of first child lactation was also observed.ConclusionThese findings suggest a protective role of exogenous hormones in gastric and colorectal cancer risk. The role of endogenous hormones remains unclear.

Comparative analysis of gene expression profiles of gastric cardia adenocarcinoma and gastric non-cardia adenocarcinoma.

In the present study, gene expression profiles were analyzed to identify the molecular mechanisms underlying gastric cardia adenocarcinoma (GCA) and gastric non-cardia adenocarcinoma (GNCA). A gene expression dataset (accession number GSE29272) was downloaded from Gene Expression Omnibus, and consisted of 62 GCA samples and 62 normal controls, as well as 72 GNCA samples and 72 normal controls. The two groups of differentially-expressed genes (DEGs) were compared to obtain common and unique DEGs. A differential analysis was performed using the Linear Models for Microarray Data package in R. Functional enrichment analysis was conducted for the DEGs using the Database for Annotation, Visualization and Integrated Discovery. Protein-protein interaction (PPI) networks were constructed for the DEGs with information from the Search Tool for the Retrieval of Interacting Genes. Subnetworks were extracted from the whole network with Cytoscape. Compared with the control, 284 and 268 genes were differentially-expressed in GCA and GNCA, respectively, of which 194 DEGs were common between GCA and GNCA. Common DEGs [e.g., claudin (CLDN)7, CLDN4 and CLDN3] were associated with cell adhesion and digestion. GCA-unique DEGs [e.g., MAD1 mitotic arrest deficient like 1, cyclin (CCN)B1, CCNB2 and CCNE1] were associated with the cell cycle and the regulation of cell proliferation, while GNCA-unique DEGs (e.g., GATA binding protein 6 and hyaluronoglucosaminidase 1) were implicated in cell death. A PPI network with 141 nodes and 446 edges were obtained, from which two subnetworks were extracted. Genes [e.g., fibronectin 1, collagen type I α2 chain (COL1A2) and COL1A1] from the two subnetworks were implicated in extracellular matrix organization. These common DEGs could advance our understanding of the etiology of gastric cancer, while the unique DEGs in GCA and GNCA could better define the properties of specific cancers and provide potential biomarkers for diagnosis, prognosis or therapy.

Correlation of p53 overexpression with the clinicopathological prognostic factors in gastric adenocarcinoma

Background: Gastric cancer is one of the leading causes of cancer deaths. The etiology of gastric cancer is complex multistep process characterised by histopathologic precursor lesions and molecular genetic alterations involving APC, K-ras and p53 genes. Overexpression of p53 in gastric carcinoma is associated with bad prognosis. Aim: To establish correlation between p53 overexpression and clinicopathological features of gastric carcinoma. Materials and methods: A cross-sectional, descriptive hospital based study of clinical, histopathological and immunohistochemistry (IHC) features of gastric carcinoma was conducted on gastrectomy specimens received to the Department of Pathology from January 2008 to June 2013. The clinical features, tumour morphology and p53 status by immunohistochemistry, were evaluated in each case. Results: The most common histologic type of gastric carcinoma was of intestinal type and predominantly were grade III tumours (60%). Most (75%) of them presented with lymph node metastasis. Majority were in stage IIIA (27.5%) or stage IV (20.0%). Majority of gastric carcinomas (35%) had 1+ intensity of p53 expression but and it was not statistically significant. Majority of gastric adenocarcinomas showed p53 positivity in <5% tumour cells. Overall, 62.5% gastric adenocarcinomas showed p53 positivity and 10 out of 40 (25%) were intensely positive. There was no significant correlation between p53 status and age of patient, tumor site, tumor size, histological type, grade, lymph node status and TNM stage. Conclusion: Mutation in p53 plays a vital role in development of gastric carcinoma. However, a significant correlation between gastric carcinoma and clinicopathological parameters could not be established. A prolonged follow up study on a large number of cases can help to find out whether p53 overexpression by standard IHC could be a useful marker for prognosis of gastric carcinoma.

GFRA3 promoter methylation may be associated with decreased postoperative survival in gastric cancer.

BackgroundA large number of epigenetic alterations has been found to be implicated in the etiology of gastric cancer. We have studied the DNA methylation status of 27 500 gene promoter regions in 24 gastric adenocarcinomas from a Norwegian cohort, and aimed at identifying the hypermethylated regions. We have compared our findings to the gene expression in the same tissue, and linked our results to prognosis and survival.MethodsBiopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 24 patients following surgical resection of the tumor. Genome-wide DNA methylation profiling of the tumor and matched non-cancerous mucosa was performed. The results were compared to whole transcriptome cDNA microarray analysis of the same material.ResultsMost of the gene promoter regions in both types of tissue showed a low degree of methylation, however there was a small, but significant hypermethylation of the tumors. Hierarchical clustering showed separate grouping of the tumor and normal tissue. Hypermethylation of the promoter region of the GFRA3 gene showed a strong correlation to post-operative survival and several of the clinicopathological parameters, however no difference was found between the two main histological types of gastric cancer. There was only a modest correlation between the DNA methylation status and gene expression.ConclusionsThe different DNA methylation clusters of the tumors and normal tissue indicate that aberrant DNA methylation is a distinct feature of gastric cancer, although there is little difference in the overall, and low, methylation levels between the two tissue types. The GFRA3 promoter region showed marked hypermethylation in almost all tumors, and its correlation with survival and other clinicopathological parameters may have important prognostic significance.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-016-2247-8) contains supplementary material, which is available to authorized users.

Ethnic Variations in Gastric cancer in a tertiary care centre of Sikkim in North-East India.

The etiology of gastric cancer is multifactorial. Marked differences in the incidence of gastric cancer among different ethnic groups living in the same geographical area have been observed. This study looked at ethnic and dietary factors in patients with gastric cancer diagnosed at a tertiary referral centre in Sikkim over a period of one year. Patients of 60 years and above were included in the study and divided into four ethnic groups : Bhutias, Lepchas, Rais and other groups. 211 cases underwent upper GI endoscopy and 32 were diagnosed to have gastric cancer. Gastric cancer incidence was highest in Bhutia ethnic group. A trend towards higher intake of smoked meats, fermented vegetables, salt tea, and H.pylori positivity in the Bhutia ethnic group was associated with higher incidence of gastric cancer as compared to other ethnic groups. The study with a referral centre bias showed that Bhutia ethnic group had a higher incidence of gastric cancer as compared to other ethnic groups.

Chronicles of a cancer foretold: 35 years of gastric cancer risk assessment

In 1980, an international group of pathologists and clinicians led by Basil Morson published a critical review entitled Precancerous Conditions and Epithelial Dysplasia in the Stomach. 1 This seminal article...

A proteomics based approach for the identification of gastric cancer related markers.

Gastric cancer (GC) is the amongst the most common cancer types causing second largest number of cancer related deaths globally. GC is characterized as an aggressive malignancy which is very tough to be detected at an early stage. GC has been defined as a complex, multistep process involving multiple genetic and epigenetic alterations leading to aberrant expression of key regulating factors. GC according to WHO has been defined as malignant epithelial tumors of the gastric mucosa with glandular differentiation. About one half of the GCs are located in the lower stomach, and remaining is located in the corpus and fundus of the stomach (20%), lesser curvature (20%), cardia (10%) and greater curvature (3%). GC has been classified into intestinal and diffuse types based on epidemiological and clinico- and histopathological features. The etiology of GC is multifactorial and includes dietary as well as non-dietary factors. Despite a lot of research efforts, GC remains to be the cancer without clear symptoms at onset, poor prognosis, with metastasis and recurrence. Thus, there is an urgent need for identifying novel and diagnostic GC biomarkers and techniques with high sensitivity and specificity. In the present review, we provide a synopsis of proteomics based GC biomarkers discovered from various cancerous specimens such as blood, gastric fluid, tissues, cells and H. pylori infected cancer cell lines. The advent of proteomics based GC biomarkers will be a great asset for the early detection and treatment of GC.