Colonoscopy plays an important role in detecting colorectal neoplasms in patients with gastric neoplasms

BACKGROUND Gastric cancer(GC)and colorectal cancer(CRC)are the fifth and third most common cancer worldwide,respectively.Nowadays,GC is reported to have a potential predictive value for CRC,especially for advanced CRC.AIM To evaluate the necessity of colonoscopy for gastric neoplasm(GN)patients.METHODS Four databases,including PubMed,EMBASE,the Cochrane Library,and Ovid,were used to perform the search strategy on May 2,2023.The prevalence of colorectal neoplasms(CRN)and baseline characteristics were compared between the neoplasm group and the control group.Continuous variables are expressed as the mean difference and standard deviation.Relationships of categorical variables in the two groups are expressed as odds ratios(OR)and 95%confidence intervals(95%CIs).Subgroup analysis according to different kinds of GNs was conducted for more in-depth analysis.The results of this study are represented by forest plots.Publication bias was evaluated by a funnel plot.All data analyses were performed by STATA SE 16.0 software.RESULTS A total of 3018 patients with GNs and 3905 healthy controls(age and sex matched)were enrolled for analysis.After comparing the prevalence of CRNs between the two groups,CRNs were detected significantly more frequently in GN patients than in controls(OR=1.69,95%CI=1.28 to 2.23,I^(2)=85.12%,P=0.00),especially in patients with GC(OR=1.80,95%CI=1.49 to 2.18,I^(2)=25.55%,P<0.1).Moreover,other risk factors including age(OR=1.08,95%CI=1.00 to 1.17,I^(2)=90.13%,P=0.00)and male sex(OR=2.31,95%CI=1.26 to 4.22,I^(2)=87.35%,P=0.00),were related to the prevalence of CRNs.For patients in the GN group,body mass index(BMI,OR=0.88,95%CI=0.80 to 0.98,I^(2)=0.00%,P=0.92)and smoking(OR=1.03,95%CI=1.01 to 1.05,I^(2)=0.00%,P=0.57)were protective and risk factors for CRNs,respectively.CONCLUSION Patients are recommended to undergo colonoscopy when diagnosed with GNs,especially GC patients with a low BMI and a history of smoking.

Estimating prognosis of gastric neuroendocrine neoplasms using machine learning:A step towards precision medicine

Survival rates following radical surgery for gastric neuroendocrine neoplasms(g-NENs)are low,with high recurrence rates.This fact impacts patient prognosis and complicates postoperative management.Traditional prognostic models,including the Cox proportional hazards(CoxPH)model,have shown limited predictive power for postoperative survival in gastrointestinal neuroectodermal tumor patients.Machine learning methods offer a unique opportunity to analyze complex relationships within datasets,providing tools and methodologies to assess large volumes of high-dimensional,multimodal data generated by biological sciences.These methods show promise in predicting outcomes across various medical disciplines.In the context of g-NENs,utilizing machine learning to predict survival outcomes holds potential for personalized postoperative management strategies.This editorial reviews a study exploring the advantages and effectiveness of the random survival forest(RSF)model,using the lymph node ratio(LNR),in predicting disease-specific survival(DSS)in postoperative g-NEN patients stratified into low-risk and high-risk groups.The findings demonstrate that the RSF model,incorporating LNR,outperformed the CoxPH model in predicting DSS and constitutes an important step towards precision medicine.

Genetic variants in C1GALT1 are associated with gastric cancer risk by influencing immune infiltration

Core 1 synthase glycoprotein-N-acetylgalactosamine 3-β-galactosyltransferase 1(C1GALT1)is known to play a critical role in the development of gastric cancer,but few studies have elucidated associations between genetic variants in C1GALT1 and gastric cancer risk.By using the genome-wide association study data from the database of Genotype and Phenotype(dbGAP),we evaluated such associations with a multivariable logistic regression model and identified that the rs35999583 G>C in C1GALT1 was associated with gastric cancer risk(odds ratio,0.83;95% confidence interval[CI],0.75-0.92;P=3.95×10^(-4)).C1GALT1 mRNA expression levels were significantly higher in gastric tumor tissues than in normal tissues,and gastric cancer patients with higher C1GALT1 mRNA levels had worse overall survival rates(hazards ratio,1.33;95%CI,1.05-1.68;P_(log-rank)=1.90×10^(-2)).Furthermore,we found that C1GALT1 copy number differed in various immune cells and that C1GALT1 mRNA expression levels were positively correlated with the infiltrating levels of CD4^(+)T cells and macrophages.These results suggest that genetic variants of C1GALT1 may play an important role in gastric cancer risk and provide a new insight for C1GALT1 into a promising predictor of gastric cancer susceptibility and immune status.

Combining lymph node ratio to develop prognostic models for postoperative gastric neuroendocrine neoplasm patients

BACKGROUND Lymph node ratio(LNR)was demonstrated to play a crucial role in the prognosis of many tumors.However,research concerning the prognostic value of LNR in postoperative gastric neuroendocrine neoplasm(NEN)patients was limited.AIM To explore the prognostic value of LNR in postoperative gastric NEN patients and to combine LNR to develop prognostic models.METHODS A total of 286 patients from the Surveillance,Epidemiology,and End Results database were divided into the training set and validation set at a ratio of 8:2.92 patients from the First Affiliated Hospital of Soochow University in China were designated as a test set.Cox regression analysis was used to explore the relationship between LNR and disease-specific survival(DSS)of gastric NEN patients.Random survival forest(RSF)algorithm and Cox proportional hazards(CoxPH)analysis were applied to develop models to predict DSS respectively,and compared with the 8th edition American Joint Committee on Cancer(AJCC)tumornode-metastasis(TNM)staging.RESULTS Multivariate analyses indicated that LNR was an independent prognostic factor for postoperative gastric NEN patients and a higher LNR was accompanied by a higher risk of death.The RSF model exhibited the best performance in predicting DSS,with the C-index in the test set being 0.769[95%confidence interval(CI):0.691-0.846]outperforming the CoxPH model(0.744,95%CI:0.665-0.822)and the 8th edition AJCC TNM staging(0.723,95%CI:0.613-0.833).The calibration curves and decision curve analysis(DCA)demonstrated the RSF model had good calibration and clinical benefits.Furthermore,the RSF model could perform risk stratification and individual prognosis prediction effectively.CONCLUSION A higher LNR indicated a lower DSS in postoperative gastric NEN patients.The RSF model outperformed the CoxPH model and the 8th edition AJCC TNM staging in the test set,showing potential in clinical practice.

Efficacy and safety of 0.4 percent sodium hyaluronate for endoscopic submucosal dissection of gastric neoplasms

AIM:To evaluate the efficacy and safety of sodium hyaluronate solution(SH) in endoscopic submucosal dissection(ESD) of gastric neoplasms.METHODS:A prospective multicenter randomized,double blind,controlled trial was designed and utilized in this study.A total of 76 patients with 5-20 mm sized gastric neoplasms were enrolled at three academic hospitals in South Korea from June 2011 to October 2011.Patients were randomly assigned to the 0.4% sodium hyaluronate or control groups.All lesions underwent endoscopic ESD.ESD was performed with 0.4%SH and normal saline(NS) solution for submucosal injection.Efficacy was assessed using en bloc resection and the number of additional injections.Secondary evaluation variables were the volume of injection material,steepness of mucosal elevation,bleeding rate,procedural time and operator satisfaction.Finally,the safety was assessed by analyzing adverse events during the study.RESULTS:The usefulness rate in the 0.4%SH group and the controlled group had statistically significant difference under intention to treat(ITT) analysis(90.91% vs 61.11% P = 0.0041).Under per protocol(PP),the usefulness rate is statistically significant different(93.10% vs 61.76%,P = 0.0036).The difference in volume of the solution injected between 0.4%SH group and the controlled group and NS group was also statistically significant under intention to treat and per protocol analysis(ITT:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0003,PP:0.03 ± 0.02 mL vs 0.06 ± 0.03 mL,P = 0.0004).Satisfaction above the grade good was significantly higher in the SH group under intention to treat and per protocol analysis(ITT:90.91% vs 61.11%,P = 0.0041,PP = 93.11% vs 61.77%,P = 0.0022).Adverse events above grade 3 were not noticed in either group.All adverse events were treated and were judged as not associated with the submucosal injection solutions.CONCLUSION:0.4%SH solution is a safe and effective agent that doesn't cause any significant adverse events and is useful for submucosal injection during ESD.

Gastric neuroendocrine neoplasms type 1: A systematic review and meta-analysis

BACKGROUND To date, the histopathological parameters predicting the risk of lymph node (LN) metastases and local recurrence, associated mortality and appropriateness of endoscopic or surgical resection in patients with gastric neuroendocrine neoplasms type 1 (GNENs1) have not been fully elucidated. AIM To determine the rate of LN metastases and its impact in survival in patients with GNEN1 in relation to certain clinico-pathological parameters. METHODS The PubMed, EMBASE, Cochrane Library, Web of Science and Scopus databases were searched through January 2019. The quality of the included studies and risk of bias were assessed using the Newcastle-Ottawa Scale (NOS) in accordance with the Cochrane guidelines. A random effects model and pooled odds ratios (OR) with 95%CI were applied for the quantitative meta-analysis. RESULTS We screened 2933 articles. Thirteen studies with 769 unique patients with GNEN1 were included. Overall, the rate of metastasis to locoregional LNs was 3.3%(25/769). The rate of LN metastases with a cut-off size of 10 mm was 15.3% for lesions > 10 mm (vs 0.8% for lesions < 10 mm) with a random-effects OR of 10.5 (95%CI: 1.4 -80.8;heterogeneity: P = 0.126;I2 = 47.5%). Invasion of the muscularis propria was identified as a predictor for LN metastases (OR: 17.2;95%CI: 1.8-161.1;heterogeneity: P = 0.165;I2 = 44.5%), whereas grade was not clearly associated with LN metastases (OR: 2;95%CI: 0.3-11.6;heterogeneity: P = 0.304;I2 = 17.4%). With regard to GNEN1 local recurrence, scarce data were available. The 5-year disease-specific survival for patients with and without LN metastases was 100% in most available studies irrespective of the type of intervention. Surgical resection was linked to a lower risk of recurrence (OR: 0.3;95%CI: 0.1-1.1;heterogeneity: P = 0.173;I2 = 31.9%). The reported complication rates of endoscopic and surgical intervention were 0.6 and 3.8%, respectively. CONCLUSION This meta-analysis confirms that tumor size ≥ 10 mm and invasion of the muscularis propria are linked to a higher risk of LN metastases in patients with GNEN1. Overall, the metastatic propensity of GNEN1 is low with favorable 5- year disease-specific survival rates reported;hence, no clear evidence of the prognostic value of LN positivity is available. Additionally, there is a lack of evidence supporting the prediction of local recurrence in GNEN1, even if surgery was more often a definitive treatment.

Secondary endoscopic submucosal dissection for locally recurrent or incompletely resected gastric neoplasms

AIM To investigate the feasibility and safety of secondary endoscopic submucosal dissection(ESD) for residual or locally recurrent gastric tumors. METHODS Between 2010 and 2017, 1623 consecutive patients underwent ESD for gastric neoplasms at a single tertiary referral center. Among these, 28 patients underwent secondary ESD for a residual or locally recurrent tumor. Our analysis compared clinicopathologic factors between primary ESD and secondary ESD groups. RESULTS The en bloc resection and curative rate of resection of secondary ESD were 92.9% and 89.3%, respectively. The average procedure time of secondary ESD was significantly longer than primary ESD(78.2 min vs 55.1 min, P = 0.004), and the adverse events rate was not significantly different but trended slightly higher in the secondary ESD group compared to the primary ESD group(10.7% vs 3.8%, P = 0.095). Patients who received secondary ESD had favorable outcomes without severe adverse events. During a mean follow-up period, no local recurrence occurred in patients who received secondary ESD. CONCLUSION Secondary ESD of residual or locally recurrent gastric tumors appears to be a feasible and curative treatment though it requires greater technical efficiency and longer procedure time.

Clinicopathological characteristics and prognosis of 232 patients with poorly differentiated gastric neuroendocrine neoplasms

BACKGROUND Poorly differentiated gastric neuroendocrine neoplasms(PDGNENs)include gastric neuroendocrine carcinoma(NEC)and mixed adenoneuroendocrine carcinoma,which are highly malignant and rare tumors,and their incidence has increased over the past few decades.However,the clinicopathological features and outcomes of patients with PDGNENs have not been completely elucidated.AIM To investigate the clinicopathological characteristics and prognostic factors of patients with PDGNENs.METHODS The data from seven centers in China from March 2007 to November 2019 were analyzed retrospectively.RESULTS Among the 232 patients with PDGNENs,191(82.3%)were male,with an average age of 62.83±9.11 years.One hundred and thirteen(49.34%)of 229 patients had a stage III disease and 86(37.55%)had stage IV disease.Three(1.58%)of 190 patients had no clinical symptoms,while 187(98.42%)patients presented clinical symptoms.The tumors were mainly(89.17%)solitary and located in the upper third of the stomach(cardia and fundus of stomach:115/215,53.49%).Most lesions were ulcers(157/232,67.67%),with an average diameter of 4.66±2.77 cm.In terms of tumor invasion,the majority of tumors invaded the serosa(116/198,58.58%).The median survival time of the 232 patients was 13.50 mo(7,31 mo),and the overall 1-year,3-year,and 5-year survival rates were 49%,19%,and 5%,respectively.According to univariate analysis,tumor number,tumor diameter,gastric invasion status,American Joint Committee on Cancer(AJCC)stage,and distant metastasis status were prognostic factors for patients with PDGNENs.Multivariate analysis showed that tumor number,tumor diameter,AJCC stage,and distant metastasis status were independent prognostic factors for patients with PDGNENs.CONCLUSION The overall prognosis of patients with PDGNENs is poor.The outcomes of patients with a tumor diameter>5 cm,multiple tumors,and stage IV tumors are worse than those of other patients.

Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms

AIM To compare the outcomes of endoscopic submucosal dissection(ESD) for gastric neoplasms using Clutch Cutter(ESD-C) or other knives(ESD-O).METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer(scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding.RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C(median; 49 min) than for ESD-O(median; 88.5 min)(P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate(100% in both groups), complete resection rate(100% in both groups), curative resection rate(86.4% vs 88.6%, P = 0.730), delayed bleeding(2.3% vs 6.8%, P = 0.62) and perforation(0% in both groups).CONCLUSION ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.

Gastric neuroendocrine neoplasms: A review

Gastric neuroendocrine neoplasms(g-NENs)or neuroendocrine tumors are generally slow-growing tumors with increasing incidence.They arise from enterochromaffin like cells and are divided into four types according to clinical characteristic features.Type 1 and 2 are gastrin dependent,whereas type 3 and 4 are sporadic.The reason for hypergastrinemia is atrophic gastritis in type 1,and gastrin releasing tumor(gastrinoma)in type 2 g-NEN.The diagnosis of g-NENs needs histopathological investigation taken by upper gastrointestinal endoscopy.g-NENs are positively stained with chomogranin A and synaptophysin.Grading is made with mitotic index and ki-67 proliferation index on histopathological analysis.It is crucial to discriminate between types of g-NENs,because the management,treatment and prognosis differ significantly between subtypes.Treatment options for g-NENs include endoscopic resection,surgical resection with or without antrectomy,medical treatment with somatostatin analogues,netazepide or chemotherapy regimens.Follow-up without excision is another option in appropriate cases.The prognosis of type 1 and 2 g-NENs are good,whereas the prognosis of type 3 and 4 g-NENs are close to the prognosis of gastric adenocancer.

Nomogram based on tumor-associated neutrophil-tolymphocyte ratio to predict survival of patients with gastric neuroendocrine neoplasms

AIM To assess the predictive value of the tumor-associated neutrophil-to-lymphocyte ratio in terms of the clinical outcomes of patients with gastric neuroendocrine neoplasms after radical surgery.METHODS Data were retrospectively collected from 142 patients who were diagnosed with gastric neuroendocrine neoplasms and who underwent radical gastrectomy at our department from March 2006 to March 2015. These data were retrospectively analyzed, and a receiver operating characteristic curve analysis was used to identify the optimal value of the tumorassociated neutrophil-to-lymphocyte ratio. Univariate and multivariate survival analyses were used to identify prognostic factors. A nomogram was then applied to predict clinical outcomes after surgery.RESULTS The tumor-associated neutrophil-to-lymphocyte ratio was significantly associated with tumor recurrence, especially with liver metastasis and lymph node metastasis(P < 0.05 for both), but not with clinical characteristics(P > 0.05 for all). A multivariate Cox regression analysis identified the tumor-associatedneutrophil-to-lymphocyte ratio as an independent prognostic factor for recurrence-free survival and overall survival(P < 0.05 for both). The concordance index of the nomograms, which included the tumorassociated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio, was 0.788(0.759) for recurrence-free survival(overall survival) and was higher than the concordance index of the traditional TNM staging system [0.672(0.663)].CONCLUSION The tumor-associated neutrophil-to-lymphocyte ratio is an independent prognostic factor in patients with gastric neuroendocrine neoplasms. Nomograms that include the tumor-associated neutrophil-to-lymphocyte ratio, Ki-67 index, and lymph node ratio have a superior ability to predict clinical outcomes of postoperative patients.

Usefulness of artificial intelligence in gastric neoplasms

Recently,studies in many medical fields have reported that image analysis based on artificial intelligence(AI)can be used to analyze structures or features that are difficult to identify with human eyes.To diagnose early gastric cancer,related efforts such as narrow-band imaging technology are on-going.However,diagnosis is often difficult.Therefore,a diagnostic method based on AI for endoscopic imaging was developed and its effectiveness was confirmed in many studies.The gastric cancer diagnostic program based on AI showed relatively high diagnostic accuracy and could differentially diagnose non-neoplastic lesions including benign gastric ulcers and dysplasia.An AI system has also been developed that helps to predict the invasion depth of gastric cancer through endoscopic images and observe the stomach during endoscopy without blind spots.Therefore,if AI is used in the field of endoscopy,it is expected to aid in the diagnosis of gastric neoplasms and determine the application of endoscopic therapy by predicting the invasion depth.

Recent advances in endoscopic management of gastric neoplasms

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy,magnification endoscopy,and narrow-band imaging,more recently supplemented by artificial intelligence,have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer(EGC)and subepithelial tumors,such as gastrointestinal stromal tumors and neuroendocrine tumors.Over the last decade,the evolution of novel advanced therapeutic endoscopic techniques,such as endoscopic mucosal resection,endoscopic submucosal dissection,endoscopic fullthickness resection,and submucosal tunneling endoscopic resection,along with the advent of a broad array of endoscopic accessories,has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery.Thus,the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection,may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists.Moreover,endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research.However,the lack of familiarity with subtle endoscopic changes associated with EGC,as well as longer procedural time,evolving resection techniques and tools,a steep learning curve of such high-risk procedures,and lack of coding are issues that do not appeal to many gastroenterologists in the field.This review summarizes recent advances in the endoscopic management of gastric neoplasms,with special emphasis on diagnostic and therapeutic methods and their future prospects.

Molecular genetics of gastric adenocarcinoma in clinical practice

The molecular genetics of gastric carcinoma(GC) dictates their biology and clinical behavior. The two morphologically distinct types of gastric carcinoma by Lauren classification, i.e., intestinal and diffuse cell types, have a significant difference in clinical outcome. These two types of GC have different molecular pathogenetic pathways with unique genetic alterations. In addition to environmental and other etiologies, intestinal type GC is associated with Helicobacter pylori(H. pylori) infection and involves a multistep molecular pathway driving the normal epithelium to intestinal metaplasia, dysplasia, and malignant transformation by chromosomal and/or microsatellite instability(MSI), mutation of tumor suppressor genes, and loss of heterozygosity among others. Diffuse type shows no clear causal relationship with H. pylori infection, but is commonly associated with deficiency of cell-cell adhesion due to mutation of the E-cadherin gene(CDH1), and a manifestation of the hereditary gastric cancer syndrome. Thus, detection of CDH1 mutation or loss of expression of E-cadherin may aid in early diagnosis or screening of diffuse type GC. Detection of certain genetic markers, for example, MSI and matrix metalloproteinases, mayprovide prognostic information, particularly for intestinal type. The common genetic alterations may offer therapeutic targets for treatment of GC. Polymorphisms in Thymidylate synthase to metabolize 5-fluorouracil, glutathione S-transferase for degradation of Cisplatin, and amplification/overexpression of human epidermal growth factor receptor 2 targeted by monoclonal antibody Trastuzumab, are a few examples. P13K/Akt/mT OR pathway, c-Met pathways, epidermal growth factor receptor, insulin-like growth factor receptor, vascular endothelial growth factor receptor fibroblast growth factor receptor, and micro RNAs are several potential therapeutic biomarkers for GC under investigation.

Multiple genetic alterations and behavior of cellular biology in gastric cancer and other gastric mucosal lesions:H.pylori infection,histological types and staging

AIM To investigate the expression of multiplegenes and the behavior of cellular biology ingastric cancer（GC）and other gastric mucosallesions and their relations to Helicobacter pylori（H.pylori）infection,tumor staging andhistological subtypes.METHODS Three hundred and twenty-sevenspecimens of gastric mucosa obtained viaendoscopy or surgical resection,and ABCimmunohistochemical staining were used todetect the expression of p53,p16,Bcl-2 andCOX-2 proteins.H.pylori was determined byrapid urea test combined with pathologicalstaining or14C urea breath test.Cellular image analysis was performed in 66 patients withintestinal metaplasia（IM）and/or dysplasia（Dys）.In 30 of them,both cancer and theparacancerous tissues were obtained at the timeof surgery.Histological pattern,tumor staging,lymph node metastasis,grading ofdifferentiation and other clinical data werestudied in the medical records.RESULTS p16 expression of IM or Dys wassignificantly lower in positive H.pylori chronicatrophic gastritis（CAG）than those withnegative H.pylori（CAG:54.8% vs 88.0%,IM:34.4% vs 69.6%,Dys:23.8% vs 53.6%,allP【0.05）,Bcl-2 or COX-2 expression of IM orDys in positive H.pylori cases was significantlyhigher than that without H.pylori（Bcl-2:68.8%vs23.9%,90.5% vs 60.7%;COX-2:50.0% vs10.8%,61.8% vs 17.8%;all P【0.05）.Themean number of most parameters of cellularimage analysis in positive H.pylori group wassignificantly higher than that in negative H.pylori group（Ellipser:53±14,40±12μm,Area1:748±572,302±202 μm2,Area2:3050±1661,1681±1990 μm2,all P【0.05;Ellipseb:79±23,58±15 μm,Ratio1:22%±5%,13%±4%,Ratio2:79%±17%,53%±20%,all P【0.01）.There was significant correlation between Bcl-2and histologic pattern of gastric carcinoma,andbetween COX-2 and tumor staging or lymph nodemetastasis（Bcl-2:75.0% vs 16.7%;COX-2:76.0% vs 20.0%,79.2% vs 16.7%;allP【0.05）.CONCLUSION p1l6, Bcl-2, and COX-2 but not p53 gene may play a role in the early genesis/ progression of gastric carcinoma and are associated with H. pylori infection. p53 gene is relatively late event in gastric tumorigenesis and mainly relates to its progression. There is more cellular-biological behavior of malignant tumor in gastric mucosal lesions with H. pylori infection. Aberrant Bcl-2 protein expression appears to be preferentially associated with the intestinal type cancer. COX-2 seems to be related to tumor staging and lymph node metastasis.

Cytochrome P450 2E1 genetic polymorphism and gastric cancer in Changle,Fujian Province

AIM: Genetic polymorphism in enzymes of carcinogen metabolism has been found to have the influence on the susceptibility to cancer. Cytochrome P450 2E1 (CYP2E1) is considered to play an important role in the metabolic activation of procarcinogens such as N-nitrosoamines and low molecular weight organic compounds. The purpose of this study is to determine whether CYP450 2E1 polymorphisms are associated with risks of gastric cancer. METHODS: We conducted a population based case-control study in Changle county, Fujian Province, a high-risk region of gastric cancer in China. Ninety-one incident gastric cancer patients and ninety-four healthy controls were included in our study. Datas including demographic characteristics, diet intake, and alcohol and tobacco consumption of individuals in our study were completed by a standardized questionnaire.PCR-RFLP revealed three genotypes:heterozygote (C1/C2) and two homozygotes (C1/C1 and C2/C2) in CYP2E1. RESULTS: The frequency of variant genotypes (C1/C2 and C2/C2) in gastric cancer cases and controls was 36.3% and 24.5%, respectively. The rare homozygous C2/C2 genotype was found in 6 individuals in gastric cancer group(6.6%), whereas there was only one in the control group (1.1%). However, there was no statistically significant difference between the two groups (two-tailed Fisher's exact test P=0.066). Individuals in gastric cancer group were more likely to carry genotype C1/C2 (odds ratio, OR=1.50) and C2/C2 (OR=7.34) than individuals in control group (chi(2) =4.597, for trend P=0.032). The frequencies of genotypes with the C2 allele (C1/C2 and C2/C2 genotypes) were compared with those of genotypes without C2 allele (C1/C1 genotype) among individuals in gastric cancer group and control group according to the pattern of gastric cancer risk factors. The results show that individuals who exposed to these gastric cancer risk factors and carry the C2 allele seemed to have a higher risk of developing gastric cancer. CONCLUSION: Polymorphism of CYP2E1 gene may have some effect in the development of gastric cancer in Changle county, Fujian Province.

Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention

Carcinoma of the stomach is still the second most common cause of cancer death worldwide, although the incidence and mortality have fallen dramatically over the last 50 years in many regions. The incidence of gastric cancer varies in different parts of the world and among various ethnic groups. Despite advances in diagnosis and treatment, the 5-year survival rate of stomach cancer is only 20 per cent. Stomach cancer can be classified into intestinal and diffuse types based on epidemiological and clinicopathological features. The etiology of gastric cancer is multifactorial and includes both dietary and nondietary factors. The major diet-related risk factors implicated in stomach cancer development include high content of nitrates and high salt intake. Accumulating evidence has implicated the role of Helicobacter pylori (H. pylori) infection in the pathogenesis of gastric cancer. The development of gastric cancer is a complex, multistep process involving multiple genetic and epigenetic alterations of oncogenes, tumor suppressor genes, DNA repair genes, cell cycle regulators, and signaling molecules. A plausible program for gastric cancer prevention involves intake of a balanced diet containing fruits and vegetables, improved sanitationand hygiene, screening and treatment of H. pylori infection, and follow-up of precancerous lesions. The fact that diet plays an important role in the etiology of gastric cancer offers scope for nutritional chemoprevention. Animal models have been extensively used to analyze the stepwise evolution of gastric carcinogenesis and to test dietary chemopreventive agents. Development of multitargeted preventive and therapeutic strategies for gastric cancer is a major challenge for the future.

Pathogenetic mechanisms in gastric cancer

Gastric cancer(GC) is a major public health issue as the fourth most common cancer and the second leading cause of cancer-related death. Recent advances have improved our understanding of its molecular pathogenesis,as best exemplified by elucidating the fundamental role of several major signaling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these signaling pathways,such as gene mutations,copy number variants,aberrant gene methylation and histone modification,nucleosome positioning,and microRNAs. Some of these genetic/epigenetic alterations represent effective diagnostic and prognostic biomarkers and therapeutic targets for GC. This information has now opened unprecedented opportunities for better understanding of the molecular mechanisms of gastric carcinogenesis and the development of novel therapeutic strategies for this cancer. The pathogenetic mechanisms of GC are the focus of this review.

Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies

Objective: In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms(SNPs) on candidate genes and gastric cancer(GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.Methods: We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30 th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability(FPRP) test.Results: Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1(rs1760944), DNMT1(rs16999593), ERCC5(rs751402), GSTT1(null/presence), MDM2(rs2278744), PPARG(rs1801282), TLR4(rs4986790), IL-17 F(rs763780), and CASP8(rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.Conclusions: Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk;however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.

Effects of dietary intake and genetic factors on hypermethyiation of the hMLH1 gene promoter in gastric cancer

AIM: Hypermethylation of the promoter of the hMLH1gene, which plays an important role in mismatch repair during DNA replication, occurs in more than 30% of human gastric cancer tissues. The purpose of this study was to investigate the effects of environmental factors, genetic polymorphisms of major metabolic enzymes, and microsatellite instability on hypermethylation of the promoter of the hMLH1 gene in gastric cancer.METHODS: Data were obtained from a hospital-based,case-control study of gastric cancer. One hundred and ten gastric cancer patients and 220 age- and sex-matched control patients completed a structured questionnaire regarding their exposure to environmental risk factors.Hypermethylation of the hMLH1 gene promoter,polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2 and L-myc genes, microsatellite instability and mutations of p53 and Ki-ras genes were investigated.RESULTS: Both smoking and alcohol consumption were associated with a higher risk of gastric cancer with hypermethylation of the hMLH1 gene promoter. High intake of vegetables and low intake of potato were associated with increased likelihood of gastric cancer with hypermethylation of the hMLH1 gene promoter. Genetic polymorphisms of the GSTM1, GSTT1, CYP1A1, CYP2E1,ALDH2, and L-mycgenes were not significantly associated with the risk of gastric cancer either with or without hypermethylation in the promoter of the hMLH1 gene.Hypermethylation of the hMLH1 promoter was significantly associated with microsatellite instability (MSI): 10 of the 14 (71.4%) MSI-positive tumors showed hypermethylation,whereas 28 of 94 (29.8%) the MSI-negative tumors were hypermethylated at the hMLH1 promoter region.Hypermethylation of the hMLH1 gene promoter was significantly inversely correlated with mutation of the p53gene.CONCLUSION: These results suggest that cigarette smoking and alcohol consumption may influence the development of hMLH1-positive gastric cancer. Most dietary factors and polymorphisms of GSTM1, GSTT1,CYP1A1, CYP2E1, ALDH2, and L-myc genes are not independent risk factors for gastric cancer with hypermethylation of the hMLH1 promoter. These data also suggest that there could be two or more different molecular pathways in the development of gastric cancer, perhaps involving tumor suppression mechanisms or DNA mismatch repair.