scholarly journals APOBEC-mediated DNA alterations: a possible new mechanism of carcinogenesis in EBV-positive gastric cancer

2018 ◽  
Author(s):  
Irina Bobrovnitchaia ◽  
Renan Valieris ◽  
Rodrigo Drummond ◽  
João Lima ◽  
Helano Freitas ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Single Nucleotide ◽  
Viral Genomes ◽  
Dna Alterations ◽  
Infected Cells ◽  
Activity Of Enzymes ◽  
Mechanism Of Carcinogenesis ◽  
Infection Response ◽  
Gastric Cancer Patients ◽  
Target Activity

AbstractMechanisms of viral oncogenesis are diverse and include the off-target activity of enzymes expressed by the infected cells, which evolved to target viral genomes for controlling their infection. Among these enzymes, the single-strand DNA editing capability of APOBECs represent a well-conserved viral infection response that can also cause untoward mutations in host DNA. Here we show, after evaluating somatic single-nucleotide variations and transcriptome data in 240 gastric cancer samples, a positive correlation between APOBEC3s mRNA-expression and the APOBEC-mutation signature, both increased in EBV+ tumors. The correlation was reinforced by the observation of APOBEC-mutations preferentially occuring in transcriptionally-active loci. The EBV-infection and APOBEC3 mutation-signature axis was confirmed in a validation cohort of 112 gastric cancer patients. Our findings suggest that APOBEC3 upregulation in EBV+ cancer may boost the mutation load, providing further clues to the mechanisms of EBV-induced gastric carcinogenesis. After further validation, this EBV-APOBEC axis may prove to be a secondary driving force in the mutational evolution of EBV+ gastric tumors, whose consequences in terms of prognosis and treatment implications should be vetted.

scholarly journals Polymorphisms in RAS/RAF/MEK/ERK Pathway Are Associated with Gastric Cancer

Genes ◽  
2018 ◽  
Vol 10 (1) ◽  
pp. 20 ◽  
Author(s):  
Patricio Gonzalez-Hormazabal ◽  
Maher Musleh ◽  
Marco Bustamante ◽  
Juan Stambuk ◽  
Raul Pisano ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Additive Model ◽  
P Value ◽  
Erk Pathway ◽  
Nucleotide Polymorphisms ◽  
Functional Effect ◽  
Cellular Functions ◽  
Single Nucleotide ◽  
Gastric Cancer Patients ◽  
Control Study

The RAS/RAF/MEK/ERK pathway regulates certain cellular functions, including cell proliferation, differentiation, survival, and apoptosis. Dysregulation of this pathway leads to the occurrence and progression of cancers mainly by somatic mutations. This study aimed to assess if polymorphisms of the RAS/RAF/MEK/ERK pathway are associated with gastric cancer. A case-control study of 242 gastric cancer patients and 242 controls was performed to assess the association of 27 single nucleotide polymorphisms (SNPs) in the RAS/RAF/MEK/ERK pathway genes with gastric cancer. Analyses performed under the additive model (allele) showed four significantly associated SNPs: RAF1 rs3729931 (Odds ratio (OR) = 1.54, 95%, confidence interval (CI): 1.20–1.98, p-value = 7.95 × 10−4), HRAS rs45604736 (OR = 1.60, 95% CI: 1.16–2.22, p-value = 4.68 × 10−3), MAPK1 rs2283792 (OR = 1.45, 95% CI: 1.12–1.87, p-value = 4.91 × 10−3), and MAPK1 rs9610417 (OR = 0.60, 95% CI: 0.42–0.87, p-value = 6.64 × 10−3). Functional annotation suggested that those variants or their proxy variants may have a functional effect. In conclusion, this study suggests that RAF1 rs3729931, HRAS rs45604736, MAPK1 rs2283792, and MAPK1 rs9610417 are associated with gastric cancer.

scholarly journals Polymorphism of MUC1 gene in Vietnamese gastric cancer patients: a case-control study

2019 ◽  
Author(s):  
Lan Thi Ngoc Nguyen ◽  
Dzung Thi Ngoc Dang ◽  
Van Thanh Ta ◽  
Huy Quang Dang ◽  
Chuc Van Tran ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Family History ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Patients ◽  
Nucleotide Polymorphisms ◽  
Mucin 1 ◽  
Single Nucleotide ◽  
History Of ◽  
Gastric Cancer Patients ◽  
Multifactor Regression

Abstract Background Gastric cancer is a malignant type of cancer associated with many factors such as environment, behavior, infection, and genetics, which include Single Nucleotide Polymorphism. A few studies revealed polymorphisms of the Mucin 1 gene have a role and significance as a susceptible factor contributing to gastric cancer. The aim of this research is to evaluate the association between Single Nucleotide Polymorphisms of the Mucin 1 gene and Vietnamese gastric cancer patients.Methods 302 gastric cancer patients and 304 controls were interviewed for social-economic characteristics, smoking and drinking status, personal and family history of gastric diseases. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism analysis. The association of Single Nucleotide Polymorphisms with gastric cancer was evaluated using multifactor regression models.Results AA genotype for rs4072037 was found to be highly associated with gastric cancer (OR: 2.07 (95% CI: 1.46-2.90). GG genotype for rs2070803 increased the risk of gastric cancer (OR:1.96 (95% CI: 1.37-2.78). These genotypes in combination with other factors such as old age, male gender, alcoholism and personal history of gastric disease also showed an increased risk of having gastric cancer.Conclusions rs4072037 and rs2070803 of Mucin 1 genes are two genotypic risk factors of gastric cancer. Those in combination with other factors such as gender, family history, smoking and drinking habits significantly increase the risk of gastric cancer.

scholarly journals Correlation between SNPs in CDH1 and gastric cancer in Chinese population

Open Medicine ◽  
2015 ◽  
Vol 10 (1) ◽  
Author(s):  
Yijin Lin ◽  
Jintao Yuan ◽  
Lihui Wang ◽  
Lan Wang ◽  
Yunjia Ma ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Single Nucleotide Polymorphisms ◽  
Cancer Patients ◽  
Chinese Population ◽  
Sequencing Analysis ◽  
Healthy Controls ◽  
Nucleotide Polymorphisms ◽  
Cdh1 Gene ◽  
Single Nucleotide ◽  
Gastric Cancer Patients

AbstractBackground. Many recent studies revealed that the single nucleotide polymorphisms have considerable effects on the susceptibility of cancer, such as prostate cancer, lung cancer and gastric cancer. The E-cadherin, a calcium-dependent transmembrane glycoprotein encoded by CDH1 gene, is critical for epithelial construction, intercellular adhesion and cell migration. Some associations have been reported between single nucleotide polymorphisms and gastric cancer in the Chinese population. Objective. To investigate whether the single nucleotide polymorphism in CDH1 gene is associated with the susceptibility of gastric cancer in the Chinese population. Material and methods. The genotypes of 5 known single nucleotide polymorphisms (rs33935154, rs121964871, rs121964874, rs121964875, rs121964876) were determined in 359 gastric cancer patients and 368 healthy controls. High resolution melting curve detection and sequencing analysis were used in the present study. Results. There is a statistical significance in the rs121964871 C>G polymorphism between gastric cancer patients and healthy controls (OR=1.769, 95%CI: 1.051-2.976). Elderly male individuals (>50 years of age) carrying this risk factor may be more susceptible to gastric cancer. Conclusions. The results indicated that the rs121964871 C>G polymorphism is associated with the susceptibility of gastric cancer in the Chinese population, with some age and sex-dependent tendencies observed.

Association of microRNA Polymorphisms with the Risk of Gastric Cancer in a Romanian Population

2017 ◽  
Vol 26 (3) ◽  
pp. 231-238 ◽  
Author(s):  
Ion Rogoveanu ◽  
Florin Burada ◽  
Mihai Gabriel Cucu ◽  
Cristin Constantin Vere ◽  
Mihai Ioana ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cancer Risk ◽  
Genetic Model ◽  
Cancer Susceptibility ◽  
Statistical Significance ◽  
Recessive Model ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Single Nucleotide ◽  
Gastric Cancer Patients

Background & Aims: MicroRNAs (miRNAs) play an important role in the occurrence and progression of human cancers, including gastric cancer. Our hospital-based case-control study aimed to investigate whether four commonly studied single nucleotide polymorphisms (SNPs) have effects on susceptibility to gastric cancer in a Romanian population.Method: We genotyped the miR-27a rs895819, miR-146a rs2910164, miR-196a2 rs11614913 and miR-499 rs3746444 SNPs by real-time PCR using predesignated TaqMan assays in 430 individuals (142 gastric cancer patients and 288 age and gender matched cancer-free controls). The associations between the investigated miRNA SNPs and gastric cancer risk were assessed by odds ratio (OR) with 95% confidence interval (CI) using logistic regression analysis.Results: A higher frequency of the miR-27a rs895819 CC genotype (OR 1.98, 95% CI: 1.05-3.73, p=0.036) was found in the patients with gastric cancer compared with the controls. Similar results were observed in a recessive model, the CC genotype was correlated with gastric cancer susceptibility (OR 1.95, 95% CI: 1.07-3.55, p=0.032). In the stratified analysis, the association between miR-27a rs895819 SNP and gastric cancer risk was limited to noncardia (OR 2.08, 95% CI: 1.10-3.94, p=0.027) and intestinal (OR 2.27, 95% CI: 1.05-4.92, p=0.042) subgroups. However, after Bonferroni correction, all associations described above lost statistical significance. No correlation was observed for the remaining SNPs and risk of gastric cancer in any genetic model studied.Conclusion: This study showed no association of the investigated miRNA SNPs with the risk of gastric cancer in a Romanian population.Key words:  –  –  – .Abbreviations: GC: gastric cancer; miRNA: microRNA; SNP: single nucleotide polymorphism.

scholarly journals Association between WNT-1-inducible signaling pathway protein-1 (WISP1) genetic polymorphisms and the risk of gastric cancer in Guangxi Chinese

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yanqiong Liu ◽  
Weijuan Qin ◽  
Fuyong Zhang ◽  
Jian Wang ◽  
Xi Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Signaling Pathway ◽  
Lower Risk ◽  
Fragment Length Polymorphism ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Downstream Target ◽  
Polymerase Chain ◽  
Gastric Cancer Patients ◽  
First Time

Abstract Background WNT1-inducible signaling pathway protein 1 (WISP1) is a member of the CCN protein family and a downstream target of β-catenin. Aberrant WISP1 expression may be involved in carcinogenesis. To date, no studies have investigated the association between single-nucleotide polymorphisms (SNPs) of WISP1 and gastric cancer. Therefore, we conducted this study to explore their relationship. Methods Polymerase chain reaction-restriction fragment length polymorphism assay was used to analyze three SNPs of WISP1 in 204 gastric cancer patients and 227 controls. Results Overall, we could not identify a significant association between WISP1 SNPs and gastric cancer risk. However, the subgroup analysis demonstrated that the presence of the rs7843546 T allele was associated with a significantly decreased risk of gastric cancer in those of Han Chinese ethnicity (CT vs. CC: OR = 0.33, 95%CI 0.14–0.78; TT vs. CC: OR = 0.29, 95%CI 0.11–0.76; CT + TT vs. CC: OR = 0.32, 95%CI 0.14–0.74). In addition, patients with the rs7843546 TT genotype display a 0.34-fold lower risk of developing stage I/II gastric cancer than those with the CC genotype Furthermore, individuals ≥ 50 years old who carried the rs10956697 AC genotype had a significantly decreased risk of gastric cancer (OR = 0.58, 95%CI 0.35–0.98). Smokers with the rs10956697 AC and AC + AA genotypes exhibited a 0.28-fold lower and 0.32-fold lower risk of gastric cancer, respectively. Conclusions The WISP1 SNPs rs7843546 and rs10956697 were, for the first time, found to reduce susceptibility to gastric cancer in various subgroups of Guangxi Chinese.

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