Gastric cancer(GC) is a highly heterogeneous malignancy. The present widely used histopathological classifications have gradually failed to meet the needs of individualized diagnosis and treatment. Development of technologies such as microarray and next-generation sequencing (NGS) has allowed GC to be studied at the molecular level. Mechanisms about tumorigenesis and progression of GC can be elucidated in the aspects of gene mutations, chromosomal alterations, transcriptional and epigenetic changes, on the basis of which GC can be divided into several subtypes. The classifications of Tan's, Lei's, TCGA and ACRG are relatively comprehensive. Especially the TCGA and ACRG classifications have large sample size and abundant molecular profiling data, thus, the genomic characteristics of GC can be depicted more accurately. However, significant differences between both classifications still exist so that they cannot be substituted for each other. So far there is no widely accepted molecular classification of GC. Compared with TCGA classification, ACRG system may have more clinical significance in Chinese GC patients since the samples are mostly from Asian population and show better association with prognosis. The molecular classification of GC may provide the theoretical and experimental basis for early diagnosis, therapeutic efficacy prediction and treatment stratification while their clinical application is still limited. Future work should involve the application of molecular classifications in the clinical settings for improving the medical management of GC.
Asian Continental Ancestry Group ; Carcinogenesis ; genetics ; Disease Progression ; Early Detection of Cancer ; Epigenesis, Genetic ; physiology ; High-Throughput Nucleotide Sequencing ; Humans ; Microarray Analysis ; Molecular Epidemiology ; standards ; Mutation ; physiology ; Prognosis ; Stomach Neoplasms ; classification ; genetics

BACKGROUND/AIMS: To identify the risk factors for metachronous gastric neoplasms in patients who underwent an endoscopic resection of a gastric neoplasm. METHODS: We prospectively collected clinicopathologic data and measured the methylation levels of HAND1, THBD, APC, and MOS in the gastric mucosa by methylation-specific real-time polymerase chain reaction in patients who underwent endoscopic resection of gastric neoplasms. RESULTS: A total of 257 patients with gastric neoplasms (113 low-grade dysplasias, 25 high-grade dysplasias, and 119 early gastric cancers) were enrolled. Metachronous gastric neoplasm developed in 7.4% of patients during a mean follow-up of 52 months. The 5-year cumulative incidence of metachronous gastric neoplasm was 4.8%. Multivariate analysis showed that moderate/severe corpus intestinal metaplasia and family history of gastric cancer were independent risk factors for metachronous gastric neoplasm development; the hazard ratios were 4.12 (95% confidence interval [CI], 1.23 to 13.87; p=0.022) and 3.52 (95% CI, 1.09 to 11.40; p=0.036), respectively. The methylation level of MOS was significantly elevated in patients with metachronous gastric neoplasms compared age- and sex-matched patients without metachronous gastric neoplasms (p=0.020). CONCLUSIONS: In patients who underwent endoscopic resection of gastric neoplasms, moderate/severe corpus intestinal metaplasia and a family history of gastric cancer were independent risk factors for metachronous gastric neoplasm, and MOS was significantly hypermethylated in patients with metachronous gastric neoplasms.
Aged ; Basic Helix-Loop-Helix Transcription Factors/genetics ; DNA Methylation ; Female ; Gastrectomy/methods ; Genes, APC/physiology ; Genes, mos/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasms, Second Primary/epidemiology/*genetics/pathology ; Proportional Hazards Models ; Risk Factors ; Stomach Neoplasms/genetics/*pathology/surgery ; Thrombomodulin/genetics

Gastric cancer is one of the most common cancers in the world. The aims of this study were to evaluate the association between polymorphisms in TFF gene family, TFF1, TFF2, and TFF3 and the risk of gastric cancer (GC) and GC subgroups in a Korean population via a case-control study. The eight polymorphisms in TFF gene family were identified by sequencing and genotyped with 377 GC patients and 396 controls by using TaqMan genotyping assay. The rs184432 TT genotype of TFF1 was significantly associated with a reduced risk of GC (odds ratio, [OR) = 0.45; 95% confidence interval, [CI] = 0.25-0.82; P = 0.009), more protective against diffuse-type GC (OR = 0.20; 95% CI = 0.05-0.89; P = 0.035) than GC (OR = 0.34; 95% CI = 0.14-0.82; P = 0.017) in subjects aged < 60 yr, and correlated with lymph node metastasis negative GC and diffuse-type GC (OR = 0.44; 95% CI = 0.23-0.86; P = 0.016 and OR = 0.20; 95% CI = 0.05-0.87; P = 0.031, respectively). In addition, a decreased risk of lymph node metastasis negative GC and diffuse-type GC was observed for rs225359 TT genotype of TFF1 (OR = 0.46, 95% CI = 0.24-0.88; P = 0.020 and OR = 0.21, 95% CI = 0.05-0.88; P = 0.033, respectively). These findings suggest that the rs184432 and rs225359 polymorphisms in TFF1 have protective effects for GC and contribute to the development of GC in Korean individuals.
Adult ; Aged ; Biomarkers, Tumor/*genetics ; Female ; Genetic Markers/genetics ; Genetic Predisposition to Disease/epidemiology/genetics ; Humans ; Incidence ; Male ; Middle Aged ; Peptides/*genetics ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Reproducibility of Results ; Republic of Korea/epidemiology ; Risk Assessment/methods ; Sensitivity and Specificity ; Stomach Neoplasms/*epidemiology/*genetics ; Tumor Suppressor Proteins/*genetics

Gastric cancer is the second leading cause of cancer-related mortality and the fourth most common cancer globally. There are, however, distinct differences in incidence rates in different geographic regions. While the incidence rate of gastric cancer has been falling, that of gastric cardia cancers is reportedly on the rise in some regions. Helicobacter pylori (H. pylori) infection is a major risk factor of non-cardia gastric cancer, and data has emerged concerning the role of H. pylori eradication for primary prevention of gastric cancer. Dietary, lifestyle and metabolic factors have also been implicated. Although addressing these other factors may contribute to health, the actual impact in terms of cancer prevention is unclear. Once irreversible histological changes have occurred, endoscopic surveillance would be necessary. A molecular classification system offers hope for molecularly tailored, personalised therapies for gastric cancer, which may improve the prognosis for patients.
Female ; Global Health ; Helicobacter Infections ; complications ; prevention & control ; Helicobacter pylori ; Humans ; Incidence ; Male ; Obesity ; complications ; Risk Factors ; Stomach Neoplasms ; epidemiology ; genetics ; microbiology ; prevention & control

BACKGROUNDIn China, esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) share susceptibility loci, but different rates of multiple primary cancer and male/female ratio suggest the proportion of familial cancer is not equal.

METHODSThe percent of cases with a positive family history, median onset age, rate of multiple primary cancer, and male/female ratio associated with upper, middle, lower third ESCC and GCA were compared to reveal the proportion of familial cancer. The 7267 subjects analyzed constituted all ESCC and GCA cases in whom the cancer was resected with cure intention between 1970 and 1994 at the 4th Hospital of Hebei Medical University.

RESULTSA positive family history for cancer was most often associated with the multiple primary ESCC and/or GCA cases, e.g. with 42% of the males and 59% of the females. For upper, middle, lower third ESCC and GCA, the percent of cases with a positive family history decreased by 38.5%, 26.3%, 26.5%, and 11.2% in males (P < 0.000) and 25.0%, 22.3%, 23.9%, and 9.8% in females (P < 0.0001). Median onset age increased from 49, 52, 55, to 56 years old in males and from 50, 53, 55, to 56 years old in females ( both P < 0.0001) for upper, middle, lower third ESCC and GCA. Male/female ratio increased from 2.2, 2.1, 2.2, to 6.2:1 for upper, middle, lower third ESCC and GCA (P < 0.0001). For upper, middle, lower third ESCC and GCA, the percent of multiple primary cancers decreased from 21.2%, 2.3%, 2.2%, to 1.5% in males and from 14.3%, 2.4%, 3.4%, to 3.1% in females. The preponderance of males, smoking, drinking, or onset-age ≥ 50 years was significantly higher in GCA than in ESCC, and the difference in the rates of multiple primary cancers between the preponderant and the non-preponderant cases was significant in GCA, but not in ESCC, suggesting non-equal requirement for genetic susceptibility when environmental hazards did not exist.

CONCLUSIONSThe proportion of familial cancer in upper gastrointestinal carcinomas decreases by the primary site of upper, middle, lower third esophagus and gastric cardia. Considering familial and sporadic cancers differ in preventability, screening strategy and recurrence, our findings have basic and clinical implications.

Adenocarcinoma ; genetics ; Age of Onset ; Carcinoma, Squamous Cell ; genetics ; Cardia ; China ; Esophageal Neoplasms ; genetics ; Female ; Genetic Loci ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Neoplasms, Multiple Primary ; epidemiology ; Risk Factors ; Stomach Neoplasms ; genetics

OBJECTIVETo explore the relationship between the polymorphisms of Toll-like receptor 2 (TLR2) and TLR9 and the susceptibility to gastric cancer.

METHODSA population-based case-control study was conducted at Linqu county, Shandong province, China, including a total of 248 cases of gastric cancer. Another total of 496 age and sex-matched controls were randomly selected from the same cohorts. TLR2 rs3804099 and TLR9 rs187084 were detected by polymerase chain reaction-restriction fragment length polymorphism method. Odds ratios (ORs) and 95% confidence interval (CI) were computed from logistic regression models after adjusting for age, sex, Helicobacter pylori (H. pylori) infection and smoking status.

RESULTSThe frequencies of TT, TC and CC genotype on TLR2 rs3804099 in control group were 43.5% (216/496), 46.6% (231/496) and 9.9% (49/496), respectively; whereas those in case group were 53.2% (132/248), 39.9% (99/248) and 6.9% (17/248), respectively. Significant differences in the frequencies of TLR2 rs3804099 were found between case and control groups (χ(2) = 6.665, P = 0.036). It was found that compared with the TT genotype, TC + CC genotype carriers obviously less susceptible to gastric cancer (OR = 0.68, 95%CI: 0.50 - 0.93). Joint effects analysis indicated that the TLR2 rs3804099 TT genotype carriers and H.pylori infectors had higher susceptibility to gastric cancer(OR = 3.42, 95%CI: 2.16 - 5.42), compared with TC + CC genotype carriers and non-H.pylori infection group. The frequencies of TT, TC and CC genotype on TLR9 rs187084 in control group were 33.3% (165/496), 49.0% (243/496) and 17.7% (88/496), respectively; whereas those in case group were 35.9% (89/248), 50.0% (124/248) and 14.1% (35/248), respectively. No significant association with gastric cancer was observed for TLR9 rs187084 polymorphism (χ(2) = 1.684, P = 0.431).

CONCLUSIONOur findings indicate that TLR2 rs3804099 is closely associated with susceptibility to gastric cancer.

Case-Control Studies ; China ; epidemiology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Stomach Neoplasms ; epidemiology ; genetics ; Toll-Like Receptor 2 ; genetics ; Toll-Like Receptor 9 ; genetics

OBJECTIVETo explore the specific and sensitive biomarkers for gastric cancer detection, a surface-enhanced laser desorption and ionization protein chip mass spectrometry (SELDI-TOF-MS) was used to generate protein profiles of serum in gastric cancer at a high-risk area.

METHODSA total of 36 gastric cancer cases and 46 subjects with superficial gastritis were selected from Linqu county, Shandong province, a high-risk area of gastric cancer. Serum samples were collected and Q10 protein chips were used to detect the serum proteomic patterns, and the sensitivity and specificity were assessed.

RESULTSFor the comparison of the gastric cancer group (26 out of 36 gastric cancer cases) versus superficial gastritis group (37 out of 46 subjects), the 6 most discriminating peaks (m/z 8587, 6945, 8243, 3899, 7035, and 9943) were identified by the ProteinChip Data Analysis System (ZUCIPDAS). The sensitivity and specificity of this pattern were 88.5% and 97.3%, respectively. A total of 19 subjects (10 gastric cancer cases and 9 superficial gastritis subjects) was selected to test the accuracy of this pattern by using blind method, and the sensitivity and specificity were 80.0% and 88.9% ,respectively.

CONCLUSIONOur findings suggest that SELDI profiling of serum might be a potential for gastric cancer detection and screening in high-risk population.

Aged ; Biomarkers, Tumor ; blood ; Blood Proteins ; genetics ; Case-Control Studies ; China ; epidemiology ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Male ; Mass Spectrometry ; Middle Aged ; Peptide Mapping ; Protein Array Analysis ; Stomach Neoplasms ; blood ; diagnosis ; epidemiology

OBJECTIVETo study the association of single nucleotide polymorphism at interleukin-10 gene 1082 locus with Helicobacter pylori (Hp) infection and the risk of gastric cancer in high prevalent region (Shaanxi Province)aand low prevalence region (Guangdong Province) in China.

METHODSThe genomic DNA was extracted from the peripheral blood of 104 healthy individuals, 104 gastric cancer patients from Guangdong Province, and from 102 healthy volunteers and 102 gastric cancer patients in Shaanxi Province, China. The single nucleotide polymorphism at IL-10 gene 1082 locus was analyzed by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The serum levels of anit-Hp IgG was measured by enzyme-linked immunosorbent assay.

RESULTSThe frequencies of IL-10-1082 A/A, A/G and G/G genotypes in the 412 subjects were 86.7%, 10.7% and 2.4%, respectively. In the low prevalence region, the number of carriers of IL-10-1082 G* was much greater in the cancer patients than in the healthy controls (14.4% vs 7.7%, Chi2=4.02, P<0.05, OR=1.01, 95% CI=1.08-3.10). The presence of IL-10-1082 G* was associated with significantly increased risk of gastric cancer following Hp infection (Chi(2)=5.36, P<0.05, OR=6.0, 95% CI=1.23-17.52). In the high prevalence region, the frequency of IL-10-1082 G* was slightly higher among the cancer patients than in the healthy controls, but this difference was not statistically significant (12.7% vs 16.6%, P>0.05).

CONCLUSIONThe G* genotype of IL-10 gene 1082 locus may be associated with increased risk of gastric cancer in China.

Aged ; China ; epidemiology ; Female ; Gene Frequency ; Genotype ; Humans ; Interleukin-10 ; genetics ; Male ; Middle Aged ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Risk Factors ; Stomach Neoplasms ; epidemiology ; genetics

OBJECTIVE: To explore the risk factors of gastric cancer in the rural area of Henan province. METHODS: Three hundred and twenty-five families with gastric cancer and 325 control families (1010 persons in each group) were selected among the rural residents in 4 counties of Henan province. Totally 2020 people were surveyed and assessed using population-based case-control family study. RESULTS: Gastric cancer was related to stomach upset, irregular dietary, hobby for salty taste, residual food, and history of mental stimulus. CONCLUSION Stomach upset, irregular dietary, hobby for salty taste, residual food, and history of mental stimulus are the risk factors of gastric cancer.
Case-Control Studies ; China ; epidemiology ; Feeding Behavior ; Humans ; Risk Factors ; Rural Population ; Stomach Neoplasms ; etiology ; genetics ; Surveys and Questionnaires

OBJECTIVETo characterize the clinical features of Chinese hereditary nonpolyposis colorectal cancer (HNPCC) families and to evaluate the value of Chinese HNPCC criteria.

METHODSTwenty-six families were involved in this study. Eight families fulfilled both the Amsterdam criteria and the Chinese HNPCC criteria (named group A), while the other 18 families fulfilled the Chinese HNPCC criteria only (named group B). The clinical features of these HNPCC families were compared with those of 509 sporadic colorectal cancers (CRC) cases. Features of families in group A and in group B were also compared and analyzed.

RESULTSA total of 86 colorectal carcinomas developed in 77 patients in these 26 families. Synchronous or metachronous colorectal cancers developed in seven (9.1%) patients. Thirty-nine percent of colorectal carcinomas were developed in the proximal colon. Fifty-one out of 71 patients (71.8%) were diagnosed before the age of 50. A total of 24 extracolonic malignancies were identified in these families. Gastric carcinoma was the most common type of extracolonic malignancy (37.5%). Compared with sporadic CRCs, HNPCC patients were significantly younger at the age of diagnosis, namely, higher proportion of patients less than 50 years old, and more frequent development of multiple colorectal cancers. Except for the average number of colorectal carcinomas developed per family (4.5:2.3, P = 0.022), there was no significant difference between group A and B regarding the age of diagnosis, the location of colorectal cancer, the development of multiple colorectal cancers and the distribution of extra-colonic malignancies.

CONCLUSIONChinese HNPCC families have certain specific clinico-pathological features. Families in accord with the Chinese HNPCC criteria have similar clinical features as those with the Amsterdam criteria. The Chinese criteria are, however, more suitable for the diagnosis of patients from small families.

Adult ; Age of Onset ; Asian Continental Ancestry Group ; genetics ; Colorectal Neoplasms, Hereditary Nonpolyposis ; epidemiology ; genetics ; Family ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasms, Second Primary ; epidemiology ; genetics ; Pedigree ; Phenotype ; Stomach Neoplasms ; epidemiology ; genetics