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 Characterization and risk association of polymorphisms in Aurora kinases A, B and C with genetic susceptibility to gastric cancer development

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Aner Mesic ◽  
Marija Rogar ◽  
Petra Hudler ◽  
Nurija Bilalovic ◽  
Izet Eminovic ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factors ◽  
In Silico ◽  
In Silico Analysis ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Mitotic Kinases ◽  
Genes Encoding ◽  
Silico Analysis ◽  
Control Study

Abstract Background Single nucleotide polymorphisms (SNPs) in genes encoding mitotic kinases could influence development and progression of gastric cancer (GC). Methods Case-control study of nine SNPs in mitotic genes was conducted using qPCR. The study included 116 GC patients and 203 controls. In silico analysis was performed to evaluate the effects of polymorphisms on transcription factors binding sites. Results The AURKA rs1047972 genotypes (CT vs. CC: OR, 1.96; 95% CI, 1.05–3.65; p = 0.033; CC + TT vs. CT: OR, 1.94; 95% CI, 1.04–3.60; p = 0.036) and rs911160 (CC vs. GG: OR, 5.56; 95% CI, 1.24–24.81; p = 0.025; GG + CG vs. CC: OR, 5.26; 95% CI, 1.19–23.22; p = 0.028), were associated with increased GC risk, whereas certain rs8173 genotypes (CG vs. CC: OR, 0.60; 95% CI, 0.36–0.99; p = 0.049; GG vs. CC: OR, 0.38; 95% CI, 0.18–0.79; p = 0.010; CC + CG vs. GG: OR, 0.49; 95% CI, 0.25–0.98; p = 0.043) were protective. Association with increased GC risk was demonstrated for AURKB rs2241909 (GG + AG vs. AA: OR, 1.61; 95% CI, 1.01–2.56; p = 0.041) and rs2289590 (AC vs. AA: OR, 2.41; 95% CI, 1.47–3.98; p = 0.001; CC vs. AA: OR, 6.77; 95% CI, 2.24–20.47; p = 0.001; AA+AC vs. CC: OR, 4.23; 95% CI, 1.44–12.40; p = 0.009). Furthermore, AURKC rs11084490 (GG + CG vs. CC: OR, 1.71; 95% CI, 1.04–2.81; p = 0.033) was associated with increased GC risk. A combined analysis of five SNPs, associated with an increased GC risk, detected polymorphism profiles where all the combinations contribute to the higher GC risk, with an OR increased 1.51-fold for the rs1047972(CT)/rs11084490(CG + GG) to 2.29-fold for the rs1047972(CT)/rs911160(CC) combinations. In silico analysis for rs911160 and rs2289590 demonstrated that different transcription factors preferentially bind to polymorphic sites, indicating that AURKA and AURKB could be regulated differently depending on the presence of particular allele. Conclusions Our results revealed that AURKA (rs1047972 and rs911160), AURKB (rs2241909 and rs2289590) and AURKC (rs11084490) are associated with a higher risk of GC susceptibility. Our findings also showed that the combined effect of these SNPs may influence GC risk, thus indicating the significance of assessing multiple polymorphisms, jointly. The study was conducted on a less numerous but ethnically homogeneous Bosnian population, therefore further investigations in larger and multiethnic groups and the assessment of functional impact of the results are needed to strengthen the findings.

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.

Antioxidant-rich diet, GSTP1 rs1871042 polymorphism, and gastric cancer risk in a hospital-based case-control study

2020 ◽  
Author(s):  
Jimi Kim ◽  
Hyejin Kim ◽  
Jeonghee Lee ◽  
Il Ju Choi ◽  
Young-Il Kim ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Case Control Study ◽  
Total Phenolics ◽  
Nucleotide Polymorphisms ◽  
Gastric Cancer Risk ◽  
Glutathione S Transferase ◽  
Single Nucleotide ◽  
Dietary Antioxidant ◽  
H Pylori ◽  
Control Study

Abstract Background Chronic gastritis along with Helicobacter pylori (H. pylori) infection has been implicated in inflammatory response-related genes linked to the causation of gastric cancer (GC). Glutathione S-transferase Pi (GSTP1) plays a role in regulating oxidative stress and detoxification against carcinogenesis. In this study, we aimed to determine whether an antioxidant-rich diet was associated with GC risk and to identify how the association could be altered by GSTP1 genetic variants. Methods The study was conducted with 1,245 participants (415 cases and 830 controls) matched for age and sex. Dietary antioxidant capacity was estimated based on oxygen radical absorbance capacity (ORAC) incorporated with a semiquantitative food frequency questionnaire. Five single nucleotide polymorphisms (SNPs) of GSTP1 (rs1695, rs749174, rs1871042, rs4891, and rs947895) were selected among the exome array genotype data. Results High dietary ORAC showed inverse associations with GC (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.57, 0.39–0.82, P = 0.004; lipophilic ORAC = 0.66, 0.45–0.95, P = 0.021; total phenolics = 0.57, 0.39–0.83, P = 0.005). The polymorphism of rs1871042 increased GC risk (OR, 95% CI = 1.55, 1.10–2.16, P = 0.01, CT + TT vs. CC). A remarkably reduced risk of GC was observed among those who had a high dietary ORAC according to rs1871042 polymorphism (hydrophilic ORAC OR T3 vs. T1, 95% CI = 0.36, 0.17–0.78, P for trend = 0.013; lipophilic ORAC = 0.58, 0.37–0.93, P for trend = 0.021; total phenolics = 0.38, 0.17–0.83, P for trend = 0.019). Conclusions Our findings indicate that the association between dietary ORAC intake and GSTP1 polymorphisms as they pertain to the risk of GC may present new intervention strategies for GC patients.

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.

Genetic polymorphisms of Cathepsin B are associated with gastric cancer risk and prognosis in a Chinese population

2021 ◽  
pp. 1-10
Author(s):  
Xiang Ma ◽  
Younan Wang ◽  
Hao Fan ◽  
Chuming Zhu ◽  
Wangwang Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Genetic Polymorphisms ◽  
Cathepsin B ◽  
Case Control Study ◽  
Nucleotide Polymorphisms ◽  
Sequencing Technology ◽  
Single Nucleotide ◽  
Polymerase Chain ◽  
Control Study

BACKGROUND: Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. OBJECTIVE: In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. METHODS: All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. RESULTS: The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p< 0.001; HR = 0.86, P= 0.019; HR = 0.85, P= 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p= 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44–0.88). CONCLUSION: Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis.

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.

scholarly journals Ornithine Decarboxylase (ODC1) gene variant (rs2302615) is associated with gastric cancer independently of Helicobacter pylori CagA serostatus

2021 ◽  
Author(s):  
Anna K Miller ◽  
Gloria Tavera ◽  
Ricardo Dominguez ◽  
M Constanza Camargo ◽  
Tim Waterboer ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Helicobacter Pylori ◽  
Ornithine Decarboxylase ◽  
Case Control Study ◽  
Population Based ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Snp Association ◽  
High Incidence ◽  
Control Study

The primary cause of gastric cancer is chronic infection with Helicobacter pylori (H.pylori) , particularly the high-risk genotype cagA, and risk modification by human genetic variants. We studied 94 variants in 54 genes for association with gastric cancer, including rs2302615 in ornithine decarboxylase (ODC1), which may affect response to chemoprevention with the ODC inhibitor, eflornithine (difluoromethylornithine; DFMO). Our population-based, case-control study included 1366 individuals (664 gastric cancer cases and 702 controls) from Western Honduras, a high incidence region of Latin America. CagA seropositivity was strongly associated with cancer (OR = 3.6; 95% CI:2.6, 5.1). The ODC1 variant rs2302615 was associated with gastric cancer (OR = 1.36; p= 0.018) in a model adjusted for age, sex, and CagA serostatus. Two additional single nucleotide polymorphisms (SNPs) in CASP1 (rs530537) and TLR4 (rs1927914) genes were also associated with gastric cancer. The ODC1 SNP association with gastric cancer was stronger in individuals who carried the TT genotype at the associating TLR4 polymorphism, rs1927914 (OR = 1.77; p = 1.85 x 10-3). In conclusion, the ODC1 variant, rs2302615, is associated with gastric cancer and supports chemoprevention trials with DFMO, particularly in individuals homozygous for the risk allele, C, at rs2302615.

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