Gastric Cancer In Chinese Population Research Articles

Evaluation of neoadjuvant immunotherapy plus chemotherapy in Chinese surgically resectable gastric cancer: a pilot study by meta-analysis.

Recently, the use of immunochemotherapy in the treatment of advanced gastric cancer (GC) has been increasing and programmed cell death protein 1 (PD-1) inhibitors combined with chemotherapy has become the first-line treatment for advanced GC. However, few studies with small sample sizes have examined this treatment regimen to assess its effectiveness and safety in the neoadjuvant treatment phase of resectable local advanced GC. Herein, we systematically searched PubMed, Cochrane CENTRAL, and Web of Science for clinical trials on neoadjuvant immunochemotherapy (nICT) in advanced GC. The primary outcomes were effectiveness [evaluated by major pathological response (MPR) and pathological complete response (pCR)] and safety [assessed by grade 3-4 treatment-related adverse events (TRAEs) and postoperative complications]. A meta-analysis of non-comparative binary results was performed to aggregate the primary outcomes. Direct comparative analysis was used to compare pooled results of neoadjuvant chemotherapy (nCT) with nICT. The outcomes emerged as risk ratios (RR). Five articles with 206 patients were included, and all of them were from the Chinese population. The pooled pCR and MPR rates were 26.5% (95% CI: 21.3%-33.3%) and 49.0% (95% CI: 42.3%-55.9%), while grade 3-4 TRAEs and post-operative complication rates were 20.0% (95% CI: 9.1%-39.8%) and 30.1% (95% CI: 23.1%-37.9%), respectively. Direct comparison showed that with the exception of grade 3-4 TRAEs and postoperative complications, all outcomes including pCR, MPR, and R0 resection rate favoured nICT to nCT. nICT is a promising strategy for use as an advisable neoadjuvant treatment for patients with advanced GC in Chinese population. However, more phase III randomized controlled trials (RCTs) will be required to further consolidate the efficacy and safety of this regimen.

Development, validation, and evaluation of a risk assessment tool for personalized screening of gastric cancer in Chinese populations

BackgroundEffective risk prediction models are lacking for personalized endoscopic screening of gastric cancer (GC). We aimed to develop, validate, and evaluate a questionnaire-based GC risk assessment tool for risk prediction and stratification in the Chinese population.MethodsIn this three-stage multicenter study, we first selected eligible variables by Cox regression models and constructed a GC risk score (GCRS) based on regression coefficients in 416,343 subjects (aged 40–75 years) from the China Kadoorie Biobank (CKB, development cohort). In the same age range, we validated the GCRS effectiveness in 13,982 subjects from another independent Changzhou cohort (validation cohort) as well as in 5348 subjects from an endoscopy screening program in Yangzhou. Finally, we categorized participants into low (bottom 20%), intermediate (20–80%), and high risk (top 20%) groups by the GCRS distribution in the development cohort.ResultsThe GCRS using 11 questionnaire-based variables demonstrated a Harrell’s C-index of 0.754 (95% CI, 0.745–0.762) and 0.736 (95% CI, 0.710–0.761) in the two cohorts, respectively. In the validation cohort, the 10-year risk was 0.34%, 1.05%, and 4.32% for individuals with a low (≤ 13.6), intermediate (13.7~30.6), and high (≥ 30.7) GCRS, respectively. In the endoscopic screening program, the detection rate of GC varied from 0.00% in low-GCRS individuals, 0.27% with intermediate GCRS, to 2.59% with high GCRS. A proportion of 81.6% of all GC cases was identified from the high-GCRS group, which represented 28.9% of all the screened participants.ConclusionsThe GCRS can be an effective risk assessment tool for tailored endoscopic screening of GC in China. Risk Evaluation for Stomach Cancer by Yourself (RESCUE), an online tool was developed to aid the use of GCRS.

Assessment of the efficacy and safety of intraperitoneal chemotherapy in patients with advanced gastric cancer in Chinese population: a meta-analysis

To investigate the safety and efficacy of intraoperative intraperitoneal chemotherapy in treating advanced gastric cancer. A randomized controlled trial (RCT) of gastric cancer surgery combined with intraoperative intraperitoneal chemotherapy for the efficacy and safety were screened by computer search PubMed, Medline, Springer, Elsevier Science Direct, Weipu, Wanfang and China National Knowledge Infrastructure (CNKI) with the last report up to October 2019. The control group underwent radical gastrectomy, and the experimental group underwent intraoperative intraperitoneal chemotherapy and radical gastrectomy. A total of 997 (Experimental group 453; Control group 544) participants were considered in this meta-analysis. Compared with the control group, the experimental group has higher 1-year survival rate [OR=2.40, 95%CI (1.34, 4.33), P=0.003], 2-year survival rate [OR=3.45, 95%CI (2.08, 5.75), P<0.00001], 3-year survival rate [OR=2.70, 95%CI (2.05, 3.54), P<0.00001] and 5-year survival rate [OR=2.90, 95%CI (1.93, 4.37), P<0.00001]. There is no significant difference in postoperative bleeding (P=0.95), postoperative infection (P=0.26), postoperative anastomotic leakage (P=0.41), and postoperative intestinal obstruction (P=0.11). Intraoperative intraperitoneal chemotherapy with advanced gastric cancer in the Chinese population can improve patients’ survival rate after surgery and does not increase the incidence of postoperative complications, so it is clinically significant and safe.

Diagnostic value of exosome derived long noncoding RNA in gastric cancer in Chinese population: A PRISMA-compliant systematic review and meta-analysis.

Background:Objective to systematically evaluate the diagnostic value of long noncoding RNA (lncRNA) in gastric cancer (GC) in the Chinese population.Methods:PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, and Wanfang Database were searched. According to the search strategy and inclusion and exclusion criteria, 2 staff members screened the relevant kinds of literature from January 2010 to December 2020 and extracted the relevant data. Revman5.3, Meta-Disc1.4, and Stata15.1 software were used to analyze the relationship between lncRNA from exosomes and the diagnosis of GC. The combined values of sensitivity (SEN), specificity (SPE), positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio (DOR) and their corresponding 95% confidence intervals (CIs) were calculated. The summary receiver operating characteristic curve was drawn and the area under the ROC curve (AUC) value was calculated.Results:In 9 studies, 1314 samples were included, including 792 cases in the case group and 522 cases in the control group. The combined SEN was 0.82 (95% CI: 0.77–0.86), the combined SPE was 0.78 (95% CI: 0.72–0.83), the combined positive likelihood ratio was 3.7 (95% CI: 2.9–4.6), the negative likelihood ratio was 0.23 (95% CI: 0.18–0.29), and the DOR was 16 (95% CI: 12–23), AUC was 0.87 (95% CI: 0.84–0.90). Subgroup analysis showed that the SEN, SPE, likelihood ratio, DOR, and AUC of plasma-derived lncRNA in the diagnosis of GC were better than those of serum.Conclusions:Exosome-derived lncRNA may be a new potential biomarker for the clinical diagnosis of GC.

Identification and epidemiological evaluation of gastric cancer risk factors: based on a field synopsis and meta-analysis in Chinese population.

To summarize and assess the credibility and strength of non-genetic factors and genetic variation on gastric cancer risk, we performed a field synopsis and meta-analysis to identify the risk of gastric cancer in Chinese population. Cumulative evidence was graded according to the Venice criteria, and attributable risk percentage (ARP) and population attributable risk percentage (PARP) were used to evaluate the epidemiological effect. A total of 956 studies included non-genetic (404 studies) and genetic factors (552 studies) were quantified, and data on 1161 single nucleotide polymorphisms (SNPs) were available. We identified 14 non-genetic factors were significantly associated with gastric cancer risk. For the analysis of time trends, H. pylori infection rate in gastric cancer and population showed a downward trend. Meanwhile 22 variants were identified significantly associated with gastric cancer: 3 (PLCE1 rs2274223, PSCA rs2976392, MUC1 rs4072037) were high and 19 SNPs were intermediate level of summary evidence, respectively. For non-genetic factors, the top three for ARP were 54.75% (pickled food), 65.87% (stomach disease), and 49.75% (smoked and frying). For PARP were 34.22% (pickled food), 34.24% (edible hot food) and 23.66%(H. pylori infection). On the basis of ARP and PARP associated with SNPs of gastric cancer, the top three for ARP were 53.91% (NAT2, rs1799929),53.05% (NAT2 phenotype), and 42.85% (IL-10, rs1800896). For PARP (Chinese Han in Beijing) were 36.96% (VDR, rs731236), 25.58% (TGFBR2, rs3773651) and 20.56% (MUC1, rs4072037). Our study identified non-genetic risk factors and high-quality biomarkers of gastric cancer susceptibility and their contribution to gastric cancer.

A multicenter study assessing the prevalence of germline genetic alterations in Chinese gastric-cancer patients.

BackgroundApproximately 10% of patients with gastric cancer (GC) have a genetic predisposition toward the disease. However, there is scant knowledge regarding germline mutations in predisposing genes in the Chinese GC population. This study aimed to determine the spectrum and distribution of predisposing gene mutations among Chinese GC patients known to have hereditary high-risk factors for cancer.MethodsA total of 40 GC patients from 40 families were recruited from seven medical institutions in China. Next-generation sequencing was performed on 171 genes associated with cancer predisposition. For probands carrying pathogenic/likely pathogenic germline variants, Sanger sequencing was applied to validate the variants in the probands as well as their relatives.ResultsAccording to sequencing results, 25.0% (10/40) of the patients carried a combined total of 10 pathogenic or likely pathogenic germline variants involving nine different genes: CDH1 (n = 1), MLH1 (n = 1), MSH2 (n = 1), CHEK2 (n = 1), BLM (n = 1), EXT2 (n = 1), PALB2 (n = 1), ERCC2 (n = 1), and SPINK1 (n = 2). In addition, 129 variants of uncertain significance were identified in 27 patients.ConclusionsThis study indicates that approximately one in every four Chinese GC patients with hereditary high risk factors may harbor pathogenic/likely pathogenic germline alterations in cancer-susceptibility genes. The results further indicate a unique genetic background for GC among Chinese patients.

XAB2 TagSNP Is Associated with the Risk of Gastric Cancer in Chinese Population: A Case-Control Study.

XAB2 protein (xeroderma pigmentosum group A-binding protein 2) plays a significant role in the nucleotide excision repair pathway. Polymorphisms in the XAB2 gene may have an effect on the capability of DNA repair and further contribute to the risk of developing various cancers. In order to investigate the relationship between XAB2 genetic variants and the risk of gastric cancer, we performed a hospital-based case–control study. XAB2 tagSNPs were selected and then genotyped by iPlex Gold Genotyping Assay and Sequenom MassArray. By performing logistic regression analysis, odds ratio (OR) and 95% confidence interval (CI) were used to estimate the association of XAB2 tagSNPs with the risk of gastric cancer. Our results showed that XAB2 rs794078AA genotype was associated with a significantly lower risk of gastric cancer compared with GG genotype with OR (95% CI) of 0.33 (0.12–0.91). Stratified analysis indicated a significantly decreased risk for gastric cancer among smokers with rs794078AA genotype compared with nonsmokers with GG genotype (OR = 0.11, 95% CI = 0.01–0.91, p = 0.040). The gene–gene interactions by multifactor dimensionality reduction (MDR) showed that tagSNP rs794078 was the best predictive element for gastric cancers (Testing Bal. Acc = 51.68%, p = 0.055, cross-validation consistency = 9). Therefore, the XAB2 tagSNP rs794078 may play an important role in the development of gastric cancer.

Development and validation of a questionnaire-based risk scoring system to identify individuals at high risk for gastric cancer in Chinese populations.

ObjectiveThis study aimed to develop and validate a risk scoring system to identify high-risk individuals carrying malignant lesions in stomach for tailored gastric cancer screening.MethodsA gastric cancer risk scoring system (GC-RSS) was developed based on questionnaire-based predictors for gastric cancer derived from systematic literature review. To assess the capability of this system for discrimination, risk scores for 8,214 and 7,235 outpatient subjects accepting endoscopic examination in two endoscopy centers, and 32,630 participants in a community-based cohort in China were calculated to plot receiver operating characteristic curves and generate area under the curve (AUC). To evaluate the performance of GC-RSS, the screening proportion, sensitivity and detection rate ratio compared to universal screening were used under different risk score cutoff values.ResultsGC-RSS comprised nine predictors including advanced age, male gender, low body mass index (<18.5 kg/m2), family history of gastric cancer, cigarette smoking, consumption of alcohol, preference for salty food, irregularity of meals and consumption of preserved food. This tool performed well in determining the risk of malignant gastric lesions with AUCs of 0.763, 0.706 and 0.696 in three validation sets. When subjects with risk scores ≥5 were evaluated with endoscopy, nearly 50% of these endoscopies could be saved with a detection rate of over 1.5 times achieved. When the cutoff was set at 8, only about 10% of subjects with the highest risk would be offered endoscopy, and detection rates for gastric cancer could be increased 2−4 fold compared to universal screening. ConclusionsAn effective questionnaire-based GC-RSS was developed and validated. This tool may play an important role in establishing a tailored screening strategy for gastric cancer in China.

Identification of Core Prognosis-Related Candidate Genes in Chinese Gastric Cancer Population Based on Integrated Bioinformatics.

Background Gastric cancer (GC) is one of the leading causes of cancer-related mortality worldwide. There are great geographical differences in the incidence of GC, and somatic mutation rates of driver genes are also different. The present study is aimed at screening core prognosis-related candidate genes in Chinese gastric cancer population based on integrated bioinformatics for the early diagnosis and prognosis of GC. Methods In the present study, the differentially expressed genes (DEGs) in GC were identified using four microarray datasets from the Gene Expression Omnibus (GEO) database. The samples of these datasets were all from China. Functional enrichment analysis of DEGs was conducted to evaluate the underlying molecular mechanisms involved in GC. Protein-protein interaction (PPI) network and cytoHubba were performed to determine hub genes associated with GC. Gene Expression Profiling Interactive Analysis (GEPIA) and Human Protein Atlas (HPA) were performed to validate the hub genes. Results A total of 240 DEGs were obtained through the RRA method, including 80 upregulated genes and 160 downregulated genes. Upregulated genes were mainly enriched in extracellular matrix organization, extracellular matrix, and extracellular matrix structural constituent. The downregulated genes were mainly enriched in digestion, extracellular space, and oxidoreductase activity. The KEGG pathway enrichment analysis showed that the upregulated genes were mainly associated with ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway. And downregulated genes were mainly associated with the metabolism of xenobiotics by cytochrome P450, metabolic pathways, and gastric acid secretion. The transcriptional and translational expression levels of the genes including COL1A1, COL5A2, COL12A1, and VCAN were higher in GC tissues than normal tissues. Conclusion A total of four genes including COL1A1, COL5A2, COL12A1, and VCAN were considered potential GC biomarkers in the Chinese population. And ECM-receptor interaction, focal adhesion, and PI3K-Akt signaling pathway were revealed to be important mechanisms of GC. Our findings provide novel insights into the occurrence and progression of GC in the Chinese population.

Relationship between MEG3 gene polymorphism and risk of gastric cancer in Chinese population with high incidence of gastric cancer.

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.

Potential effects of IL-17A rs2275913 and IL-17F rs763780 polymorphisms on susceptibility to gastric cancer in Chinese population: a meta-analysis.

This meta-analysis aims to clarify the effect of IL-17 polymorphisms on the susceptibility to GCa in the Chinese population. Relevant pieces of literature were searched in PubMed, Web of School, VIP, and CNKI using the key words as "IL-17, gastric/stomach cancer" or "IL-17 polymorphisms, gastric/stomach cancer susceptibility". The odds ratio (OR) and 95% confidence interval (CI) in the selected studies were calculated using RevMan5.3 and STATA12.0. A total of 12 investigations reporting mutations in IL-17A rs2275913 and IL-17F rs763780 were enrolled. There were 11 studies reporting rs2275913 G>A, involving 3299 cases of GCa patients and 3339 cases of healthy controls. The random-effects model was performed since the heterogeneity test results of the recessive genetic model (GG&GA vs. AA) and the allelic model (G vs. A) of IL-17A rs2275913 G>A were I2>66%/p=0.001. Meanwhile, the dominant genetic model (GG vs. GA&AA) and the super-dominant genetic model (GA vs. GG&AA) of IL-17A rs2275913 G>A were I2< 50%/p>0.05, and the fixed-effects model was used. The meta-analysis showed that IL-17A rs2275913 G>A was positively correlated with GCa susceptibility under four genetic models (p<0.05). Five studies reporting IL-17F rs763780 T>C were enrolled, including 2535 cases of GCa patients and 2402 cases of healthy controls. The heterogeneity test showed that, except for the super-dominant genetic model, the p-value was <0.00001 in the dominant, recessive, and allelic models, and their I2 values were 87%, 88%, and 93%, respectively. Hence, a random-effects model was selected. IL-17F rs763780 T>C was positively correlated with GCa susceptibility under the super-dominant genetic model (p=0.003), rather than the other three models (p>0.05). IL-17A rs2275913 G>A polymorphism contributes to susceptibility to GCa in the dominant, recessive, allelic, and super-dominant models. Meanwhile, IL-17F rs763780 T>C polymorphism is positively correlated with GCa susceptibility in the super-dominant model.

Long non-coding RNA polymorphisms on 8q24 are associated with the prognosis of gastric cancer in a Chinese population.

BackgroundGastric cancer (GC) remains the third leading cause of cancer death in China. Although genome-wide association studies have identified the association between several single nucleotide polymorphisms (SNPs) on 8q24 and the risk of GC, the role of these SNPs in the prognosis of GC in Chinese populations has not yet been fully evaluated. Therefore, this study was conducted to explore the association between long non-coding RNA (lncRNA) polymorphisms on 8q24 and the prognosis of GC.MethodsWe genotyped 726 surgically resected GC patients to explore the association between eight SNPs in the lncRNAs CCAT1 (rs10087719, rs7816475), PCAT1 (rs1026411), PRNCR1 (rs12682421, rs13252298), and CASC8 (rs1562430, rs4871789, rs6983267) transcribed from the 8q24 locus and the prognosis of GC in a Chinese population.ResultsWe found that the patients carrying rs12682421 AA genotypes survived for a shorter time than those with the GG/GA genotype (HR = 1.39, 95% confidence interval (CI) [1.09–1.78]). Compared with the CC/CT genotype, the TT genotype of rs1562430 was associated with an increased risk of death (HR = 1.38, 95% CI [1.06–1.80]). Furthermore, the results also identified the rs1026411 SNP as an independent prognostic factor for poor survival in GC patients. Patients carrying AA/AG variant genotypes had a 36% increased risk of death compared to those carrying the GG genotype (HR = 1.36, 95% CI [1.06–1.74]). These findings suggested that the rs12682421, rs1026411 and rs1562430 SNPs may contribute to the survival of GC and be prognostic markers for GC.

Genetic and Non-Genetic Risk Factors for Gastric Cancer: A Field Synopsis and Evidence from 934 Chinese Population Studies

Background: China is one of the regions with the highest incidence, prevalence and mortality of gastric cancer worldwide. Yet, only few field synopses about non-genetic factors and genetic susceptibility in gastric carcinogenesis. The aim of this study is to summarize and assess the credibility and strength of non-genetic factors and genetic variation on the risk of gastric cancer. Methods: We used Chinese and international public databases to identify published studies that assessed associations between non-genetic factors and variants on candidate genes and the risk of gastric cancer in Chinese population. Cumulative epidemiological evidence of statistical relation was evaluate combining Venice criteria, a false-positive report probability (FPRP) test, attributable risk percentage (ARP) and population attributable risk percentage (PARP). Findings: A total of 622 articles (n=394 articles, 399 studies for non-genetic factors; n=532 articles, 535 studies for genetic factors) eligible articles were included in qualitative synthesis. A total of 16 common potential risk factors were extracted for non-genetic factors, and data on 1121 single nucleotide polymorphism (SNP) involving 441 distinct genes were available. We identified 14 non-genetic factors were significantly associated with gastric cancer risk: H. pylori infection, smoking, drinking, family history, stomach disease, high salt diet, pickled food, fast eating, irregular meals, edible hot food, smoked & frying, spicy diet, mental depression and diabetes. Meanwhile 22 variants were identified significantly associated with gastric cancer: 3 (PLCE1 rs2274223, PSCA rs2976392, MUC1 rs4072037) was high and 19 (MTHFR rs1801133, COX-2 rs20417, XRCC1 rs1799782 and rs25487, XRCC3, rs861539, NAT2 rs1799930 and rs1799929, PLCE1 rs3765524, GSTM1, GSTT1, IL-17A rs2275913 and rs8193036, PSCA rs2294008, PRKAA1 rs13361707, ERCC5 rs751402, TGFBR2 rs3773651, IL-10 rs1800896 and VDR rs731236) was intermediate level of summary evidence, respectively. As we add more non-genetic factors or susceptible genes to the model, the risk distribution expands, and the population can better distinguish high-risk and low-risk categories. For non-genetic factors, the top three for ARP were 66.33% (stomach disease), 54.34% (pickled food), and 49.75% (Smoked & frying). For PARP were 33.85% (pickled food), 24.73% (edible hot food) and 23.30% (H. pylori infection). On the basis of ARP and PARP associated with SNPs of gastric cancer, the top three for ARP were 53.91% (NAT2, rs1799929),53.05% (NAT2 phenotype), and 42.85% (IL-10, rs1800896). For PARP (CHB) were. 36.96% (VDR, rs731236), 25.58% (TGFBR2, rs3773651) and 20.56% (MUC1, rs4072037). Interpretation: We conducted the first field synopsis in Chinese population linking common non-genetic risk factors and DNA variation to summarize potential non-genetic and genetic risk factors for gastric cancer, and evaluate epidemiological indicators to identified high-quality biomarkers of gastric cancer. Our study provides referenced information for the non-genetic and genetic predisposition to gastric cancer. Funding Statement: This work was funded by the National Natural Science Foundation of China (81373097), Health Science and Technology Innovative Talents Project of Henan Province 2017, and Henan Medical Science and Technique Foundation (Co-sponsored by Province and Ministry, 2019). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study was conducted based on the Meta-analysis of Observational Studies in Epidemiology (MOOSE), Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the systematic review principles of molecular association studies proposed by the Human Genome Epidemiology Network (HuGENet).

806P - Germline pathogenic mutations in Chinese patients with gastric cancer identified by next-generation sequencing (NGS)

BackgroundGastric cancer (GC) is one of the leading cause of cancer death in China, which is mainly caused by environmental and genetic risk factors. By far, the nature of the genetic factors related to gastric cancer has not been well-studied. The aim of this study was to assess the frequency of germline mutations in Chinese gastric cancer population. MethodsGenomic profiling of DNA was performed through next-generation sequencing (NGS) on tissue or liquid biopsy from patients with gastric cancer between January 01, 2017 and May 07, 2019. Patients with germline pathogenic mutations were identified, and their clinical information were collected. Results750 gastric cancer patients were ultimately included for analysis. There were 476 (63.5%) male and 274 (36.5%) female patients. The median age was 61 (range, 26-88). A total of 27 (3.6%) pathogenic germline pathogenic mutations were identified in 13 genes from these patients. The mutations fell most frequently in BRCA2 (0.93%), ATM (0.67%), PALB2 (0.4%), CHEK2 (0.27%), and CDH1 (0.27%), which has been previously reported to underlie hereditary diffuse gastric cancer. Of all these mutations, 9 (69.2%) genes lay in the DNA damage repair pathways, including BRCA1, BRCA2, ATM, PALB2, CHEK2, MRE11A, ATR, and two DNA mismatch repair genes, MLH1 and MSH6, the mutation of which usually result in the presence of microsatellite instability (MSI) in tumor tissues. ConclusionsThis is the first study to explore the spectrum of pathogenic germline mutations in Chinese patients with gastric cancer. Our study has provided valuable clues for the assessment of the corresponding genetic susceptibility in gastric cancer. Legal entity responsible for the studyBeijing Cancer Hospital. FundingHas not received any funding. DisclosureZ. Zhao: Full / Part-time employment: 3D Medicines Inc. Y. Zhang: Full / Part-time employment: 3D Medicines Inc. S. Cai: Full / Part-time employment: 3D Medicines Inc. All other authors have declared no conflicts of interest.

Meta-analysis of genome-wide association studies and functional assays decipher susceptibility genes for gastric cancer in Chinese populations

ObjectiveAlthough a subset of genetic loci have been associated with gastric cancer (GC) risk, the underlying mechanisms are largely unknown. We aimed to identify new susceptibility genes and elucidate their...

Abstract LB-175: Genome-wide scan of the effect of cis-eSNPs on gastric cancer in Chinese population

Abstract Background: Previous genome-wide association studies (GWASs) have identified multiple single-nucleotide polymorphisms (SNPs) for gastric cancer risk. However, only a tiny fraction of heritability can be explained. Methods: We performed a comprehensive analysis to evaluate the associations between cis-expression quantitative trait SNPs (eSNPs) and susceptibility to gastric cancer in two GWAS datasets, including 2,631 gastric cancer cases and 4,373 controls. Gene-based and pathway analysis were conducted by the sequence kernel association test (SKAT-C) and the adaptive rank truncated product (ARTP) method, respectively. Results: A total of 314,518 eSNPs were remained after quality control, which mapped to 5,155 genes and 1,077 pathways. We identified six novel eQTL SNPs in unknown loci which can explain approximately 3.56% of the phenotypic variances combined with known GWAS related variants. Function analysis revealed that rs3129206 might affect the susceptibility of gastric cancer via regulating the expression of HSD17B8, while rs6930376 regulating the expression of PSORS1C3. Pathway-based analysis showed a total of seven potential pathways might account for the risk of gastric cancer (Pfdr&amp;lt;0.1). Conclusion: Our findings demonstrate an overview of the associations between eSNPs and gastric cancer risk in Chinese population, which provide insight into genes and pathways that may be biologically relevant for risk of gastric cancer. Citation Format: Jing Ni, Jing Han, Meng Zhu, Guangfu Jin, Zhibin Hu. Genome-wide scan of the effect of cis-eSNPs on gastric cancer in Chinese population [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-175.

The MDM2 rs937283 A>G variant significantly increases the risk of lung and gastric cancer in Chinese population.

Currently, the MDM2 promoter rs937283 A > G variant that is able to alter MDM2 gene expression has been widely studied to explore the association of MDM2 with cancer risk. In this report, we investigate the association of MDM2 rs937283 A > G variant with risk of lung cancer (LC) and gastric cancer(GC) in a Chinese population of Hubei province, which was followed by a meta-analysis. The genotyping of rs937283 was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. The results of the present study showed that rs937283 was significantly associated with the risk of LC, and the factors of age, gender, smoking status and drinking status would affect such association. However, rs937283 was only associated with the risk of GC in male, smoking and drinking subgroups. The following meta-analysis demonstrated that rs937283 was associated with the overall cancer risk particularly in Chinese population, which reinforced our present finding. Moreover, the meta-analysis according to cancer types revealed that rs937283 was associated with retinoblastoma risk, but not squamous cell carcinoma risk. Collectively, the MDM2 rs937283 A > G variant may be a valuable risk factor or diagnostic biomarker for Chinese cancer patients.

YpTNM staging after neoadjuvant chemotherapy in the Chinese gastric cancer population: an evaluation on the prognostic value of the AJCC eighth edition cancer staging system

BackgroundThis study aims to evaluate the new ypTNM staging system in Chinese gastric cancer patients.MethodsWe conducted retrospective survival and regression analyses using a database of gastric cancer patients who underwent neoadjuvant chemotherapy at the Peking University Cancer Hospital and Institute from January 2007 to January 2015.ResultsA total of 473 patients were included in the study with 28 pathological complete response (pCR) cases, 3 ypT0N1 cases, 65 stage I cases, 126 stage II cases, and 251 stage III cases. The pCR cases had similar survival to stage I patients (p > 0.05). The 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates of stage I, II and III patients were significantly different (3-year DFS: 89.0, 75.5, and 39.6%, p < 0.001; 5-year OS: 89.6, 65.5, and 36.5%, p = 0.001). Both ypT and ypN are independent predictors of patient survival, while further log-rank tests showed that the ypN stage is of better prognostic value than ypT. Subgrouping analysis revealed that stage III patients of ypT4b and ypN3 had worse survival compared to the rest of stage III cases (p < 0.001). The c-index values of the ypTNM stage and modified ypTNM stage (stage III divided into IIIa and IIIb) were 0.657 and 0.708, respectively (p < 0.001).ConclusionsOur data showed significant differences in survival among gastric cancer patients at different ypTNM stages, indicating its prognostic value in the Chinese population. Further detailed analyses may facilitate the subgrouping of each stage to allow for a more accurate evaluation of disease prognosis in gastric cancer patients.

Genetic Variants Within MTORC1 Genes Predict Gastric Cancer Prognosis in Chinese Populations.

Objective: Mammalian target of rapamycin complex 1 (mTORC1) plays an important role in maintaining proper cellular functions in gastric cancer (GC). Previous studies demonstrated genetic variants within mTORC1 genes were associated with GC risk. However, no studies reported the associations between genetic variants within mTORC1 genes and GC prognosis. Herein, we firstly assessed the associations of genetic variants of mTORC1 genes with overall survival (OS) of GC in Chinese populations.Methods: We genotyped eight single nucleotide polymorphisms (SNPs) in mTORC1 genes (i.e., rs2536 T>C and rs1883965 G>A for mTOR, rs3160 T>C and rs26865 A>G for MLST8, rs3751934 C>A, rs1062935 T>C, rs3751932 T>C and rs12602885 G>A for RPTOR) by the TaqMan method in 197 Chinese GC patients who had surgical resection in Xinhua Hospital. We conducted Kaplan-Meier survival plots and Cox hazards regression analysis to explore the associations of these SNPs with OS.Results: The single-locus analysis indicated that RPTOR rs1062935 T>C was associated with an increased risk of poor GC prognosis (CC vs. TT/TC: adjusted Hazard ratio (HR) = 1.71, 95% confidence interval (CI) = 1.04-2.82). The combined analysis of all eight SNPs showed that patients with more than three risk genotypes significantly increased risk of death (adjusted HR = 2.44, 95% CI = 1.30-4.58), when compared to those with three or less risk genotypes.Conclusions: Our findings indicated that genetic variants within mTORC1 genes may predict GC prognosis in Chinese populations. The results need to be validated in future studies with larger sample sizes.

The DNMT3B -579G>T Polymorphism Is Significantly Associated With the Risk of Gastric Cancer but not Lung Cancer in Chinese Population.

The -149C>T and -579G>T, 2 single nucleotide polymorphisms in de novo methyltransferase 3B gene promoter, have been previously reported to potentially alter the promoter activity and to influence cancer risk. However, the results from previous studies remain conflicting rather than conclusive. In view of this, we conducted a case–control study and then a meta-analysis to examine the association between these 2 single-nucleotide polymorphisms with risk of lung and gastric cancer in Chinese population. The genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and confirmed by sequencing. In this case–control study, no significant association with lung or gastric cancer risk was observed for -149C>T, while -579G>T was significantly correlated with the risk of gastric cancer but not lung cancer. Moreover, haplotype analysis showed that haplotype -149T/-579 T, which carried the risk -579 T allele, significantly increased the susceptibility to gastric cancer. However, none of the haplotypes was associated with the risk of lung cancer. The following meta-analysis involved only Chinese population and further confirmed the significant association of -579G>T with gastric cancer but not lung cancer and suggested no significant association between -149C>T and risk of lung or gastric cancer. Collectively, DNMT3B -579G>T polymorphism is associated with gastric cancer risk in Chinese population, and the -579G>T may be used as a genetic biomarker to predict the risk of gastric cancer in Chinese population.