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1
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Liu M, Song SS, Park S. High Polygenic Risk Scores Positively Associated with Gastric Cancer Risk Interact with Coffee and Polyphenol Intake and Smoking Status in Korean Adults. Nutrients 2024; 16:3263. [PMID: 39408230 PMCID: PMC11478441 DOI: 10.3390/nu16193263] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2024] [Revised: 09/20/2024] [Accepted: 09/25/2024] [Indexed: 10/20/2024] Open
Abstract
BACKGROUND/OBJECTIVES This study investigated the relationship between single nucleotide polymorphisms (SNPs) and gastric cancer (GC) risk, while also examining the interaction of genetic factors with lifestyle variables including the nutrient and bioactive compound intake in Korean adults of a large hospital-based cohort. METHODS We conducted a genome-wide association study (GWAS) comparing GC patients (n = 312) with healthy controls without cancers (n = 47,994) to identify relevant genetic variants. Generalized multifactor dimensionality reduction (GMDR) was employed to detect SNP interactions between diets and lifestyles. We utilized polygenic risk scores (PRSs) to assess individuals' GC risk based on multiple SNP loci. Among the selected SNPs, since SEMA3C_rs1527482 was a missense mutation, bioactive compounds which decrease the binding energy were found with its wild and mutated proteins by molecular docking analysis. RESULTS Individuals with high PRSs exhibited a 4.12-fold increased risk of GC compared to those with low PRSs. Additional factors associated with elevated GC risk included a low white blood cell count (OR = 5.13), smoking (OR = 3.83), and low coffee consumption (OR = 6.30). The SEMA3C_rs1527482 variant showed a positive correlation with GC risk. Molecular docking analyses suggested that certain polyphenols, including theaflavate, rugosin E, vitisifuran B, and plantacyanin, reduced the binding free energy in both wild-type and mutated SEMA3C_rs1527482. However, some polyphenols exhibited differential binding energies between its wild and mutated forms, suggesting they might modulate wild and mutated proteins differently. CONCLUSION High PRSs and SEMA3C_rs1527482 interact with immune function, coffee intake, polyphenol consumption, and smoking status to influence GC risk. These findings could contribute to developing personalized nutrition and lifestyle interventions to reduce GC risk.
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Affiliation(s)
- Meiling Liu
- Department of Chemical Engineering, Shanxi Institute of Science and Technology, Jincheng 048000, China;
| | - Sang-Shin Song
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea;
| | - Sunmin Park
- Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea;
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Pyun H, Gunathilake M, Lee J, Choi IJ, Kim YI, Sung J, Kim J. Functional Annotation and Gene Set Analysis of Gastric Cancer Risk Loci in a Korean Population. Cancer Res Treat 2024; 56:191-198. [PMID: 37340842 PMCID: PMC10789951 DOI: 10.4143/crt.2022.958] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2022] [Accepted: 06/17/2023] [Indexed: 06/22/2023] Open
Abstract
PURPOSE We aimed to identify the associated single nucleotide polymorphisms (SNPs) with gastric cancer (GC) risk by genome-wide association study (GWAS) and to explore the pathway enrichment of implicated genes and gene-sets with expression patterns. MATERIALS AND METHODS The study population was comprised of 1,253 GC cases and 4,827 controls from National Cancer Center and an urban community of the Korean Genome Epidemiology Study and their genotyping was performed. SNPs were annotated, and mapped to genes to prioritize by three mapping approaches by functional mapping and annotation (FUMA). The gene-based analysis and gene-set analysis were conducted with full GWAS summary data using MAGMA. Gene-set pathway enrichment test with those prioritized genes were performed. RESULTS In GWAS, rs2303771, a nonsynonymous variant of KLHDC4 gene was top SNP associated significantly with GC (odds ratio, 2.59; p=1.32×10-83). In post-GWAS, 71 genes were prioritized. In gene-based GWAS, seven genes were under significant p < 3.80×10-6 (0.05/13,114); DEFB108B had the lowest p=5.94×10-15, followed by FAM86C1 (p=1.74×10-14), PSCA (p=1.81×10-14), and KLHDC4 (p=5.00×10-10). In gene prioritizing, KLDHC4 was the only gene mapped with all three gene-mapping approaches. In pathway enrichment test with prioritized genes, FOLR2, PSCA, LY6K, LYPD2, and LY6E showed strong enrichment related to cellular component of membrane; a post-translation modification by synthesis of glycosylphosphatidylinositol (GPI)-anchored proteins pathway. CONCLUSION While 37 SNPs were significantly associated with the risk of GC, genes involved in signaling pathways related to purine metabolism and GPI-anchored protein in cell membrane are pinpointed to be playing important role in GC.
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Affiliation(s)
- Hyojin Pyun
- Division of Genome and Health Big Data, Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul,
Korea
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang,
Korea
| | - Madhawa Gunathilake
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang,
Korea
| | - Jeonghee Lee
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang,
Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang,
Korea
| | - Young-Il Kim
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang,
Korea
| | - Joohon Sung
- Division of Genome and Health Big Data, Department of Public Health Sciences, Graduate School of Public Health, Seoul National University, Seoul,
Korea
- Institute of Health and Environment, Seoul National University, Seoul,
Korea
| | - Jeongseon Kim
- Department of Cancer Biomedical Science, Graduate School of Cancer Science and Policy, Goyang,
Korea
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Nguyen NLT, Dang NDT, Dang QH, Tran VC, Vo HL, Yamaguchi M, Ta TV. Polymorphism of MUC1 Gene in Vietnamese Gastric Cancer Patients: A Multicenter Case-Control Study. Front Oncol 2021; 11:694977. [PMID: 34532288 PMCID: PMC8439541 DOI: 10.3389/fonc.2021.694977] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2021] [Accepted: 08/10/2021] [Indexed: 12/31/2022] Open
Abstract
Background A few studies revealed that the polymorphisms of Mucin 1 gene have a role and significance as a susceptible factor contributing to gastric cancer. To better understand the roles of two MUC1 genotype polymorphisms of rs4072037 and rs2070803 in the development of gastric cancer in Vietnamese population, a multicenter, large-sample, case-control study was conducted to investigate the potential association of these single-nucleotide polymorphisms (SNPs) of MUC1 gene with gastric cancer risk and to evaluate the combination factors in relation with these SNPs. Methods This case-control study included 302 gastric cancer patients and 304 controls at four national medical hospitals between 2016 and 2018. All participants were interviewed for sociodemographic characteristics, smoking and drinking status, and personal and family history of gastric diseases. Genotyping was done using polymerase chain reaction-restriction fragment length polymorphism analysis. The association of SNPs with gastric cancer was explored using logistic regression models. Results AA genotype for rs4072037 was significantly associated with increased gastric cancer. Those with AA genotype had higher gastric cancer risk than had patients with AG (OR: 2.09, 95% CI: 1.48-2.96) and a combination of AG+GG (OR: 1.85, 95% CI: 1.33-2.56). In rs2070803, GG genotype increased gastric cancer risk when compared with AG (OR: 1.97, 95% CI: 1.39-2.80) and AG+AA (OR: 1.71, 95% CI: 1.23-2.39). AG genotypes in both SNPs decreased gastric cancer risk when compared with homogenous genotype, more specifically AA (OR: 0.51, 95% CI: 0.35-0.72) and GG (OR: 0.58, 95% CI: 0.35-0.97). These genotypes in combination with above-60-year-old age, male gender, alcoholism, and personal history of gastric disease were also significantly elevated risk factors for gastric cancer. Conclusions rs4072037 and rs2070803 of Mucin 1 genes are two genotypic risk factors for gastric cancer. Those in combination with gender, family history, smoking, and drinking habits significantly increase the risk of gastric cancer.
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Affiliation(s)
- Ngoc-Lan Thi Nguyen
- Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam.,Clinical Laboratory, Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam
| | - Ngoc-Dzung Thi Dang
- Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam.,Clinical Laboratory, Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam
| | - Quang-Huy Dang
- Department of Medical Laboratory Science, Faculty of Medical Technology, Hanoi Medical University, Hanoi, Vietnam
| | - Van-Chuc Tran
- Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam
| | - Hoang-Long Vo
- Department of Scientific Research and International Cooperation, Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam
| | - Masamitsu Yamaguchi
- Department of Applied Biology, Advanced Insect Research Promotion Center, Kyoto Institute of Technology, Kyoto, Japan
| | - Thanh-Van Ta
- Biochemistry Department, Hanoi Medical University, Hanoi, Vietnam.,Clinical Laboratory, Hanoi Medical University Hospital, Hanoi Medical University, Hanoi, Vietnam
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Lifestyles, genetics, and future perspectives on gastric cancer in east Asian populations. J Hum Genet 2021; 66:887-899. [PMID: 34267306 PMCID: PMC8384627 DOI: 10.1038/s10038-021-00960-8] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2021] [Revised: 06/08/2021] [Accepted: 07/05/2021] [Indexed: 12/17/2022]
Abstract
The prevalence of gastric cancer (GC) differs among regions worldwide, with the highest occurrence in east Asia. Thus, its etiology, with respect to ethnic background, environmental factors, and lifestyles, is also thought to differ essentially. In addition, etiology of GC is speculated to be changing due to the recent decrease in the Helicobacter pylori (H. pylori) infection in Japan. State-of-the-art somatic/germline cancer genomics has clarified the etiologies of gastric carcinogenesis. In this review article, we summarize past and present milestones in our understanding of GC achieved through genomic approaches, including a recent report that revealed higher-than-expected frequencies of GCs attributed to east Asian-specific germline variants in ALDH2 or CDH1 in combination with lifestyles. Based on this updated knowledge, we also discuss the possible impact of and high-risk approaches for GCs in the upcoming "H. pylori-negative era."
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Alikhani R, Taravati A, Hashemi-Soteh MB. Association of MUC1 5640G>A and PSCA 5057C>T polymorphisms with the risk of gastric cancer in Northern Iran. BMC MEDICAL GENETICS 2020; 21:148. [PMID: 32660489 PMCID: PMC7359498 DOI: 10.1186/s12881-020-01085-z] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/21/2020] [Accepted: 07/02/2020] [Indexed: 12/25/2022]
Abstract
BACKGROUND Gastric cancer is one of the four most common cancer that causing death worldwide. Genome-Wide Association Studies (GWAS) have shown that genetic diversities MUC1 (Mucin 1) and PSCA (Prostate Stem Cell Antigen) genes are involved in gastric cancer. The aim of this study was avaluating the association of rs4072037G > A polymorphism in MUC1 and rs2294008 C > T in PSCA gene with risk of gastric cancer in northern Iran. METHODS DNA was extracted from 99 formalin fixed paraffin-embedded (FFPE) tissue samples of gastric cancer and 96 peripheral blood samples from healthy individuals (sex matched) as controls. Two desired polymorphisms, 5640G > A and 5057C > T for MUC1 and PSCA genes were genotyped using PCR-RFLP method. RESULTS The G allele at rs4072037 of MUC1 gene was associated with a significant decreased gastric cancer risk (OR = 0.507, 95% CI: 0.322-0.799, p = 0.003). A significant decreased risk of gastric cancer was observed in people with either AG vs. AA, AG + AA vs. GG and AA+GG vs. AG genotypes of MUC1 polymorphism (OR = 4.296, 95% CI: 1.190-15.517, p = 0.026), (OR = 3.726, 95% CI: 2.033-6.830, p = 0.0001) and (OR = 0.223, 95% CI: 0.120-0.413, p = 0.0001) respectively. Finally, there was no significant association between the PSCA 5057C > T polymorphism and risk of gastric cancer in all genetic models. CONCLUSION Results indicated that the MUC1 5640G > A polymorphism may have protective effect for gastric cancer in the Northern Iran population and could be considered as a potential molecular marker in gastric cancer.
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Affiliation(s)
- Reza Alikhani
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran
| | - Ali Taravati
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Mazandaran, Iran
| | - Mohammad Bagher Hashemi-Soteh
- Immunogenetic Research center, Molecular and Cell Biology Research Center, Medical Faculty, Mazandaran University of Medical Sciences, Sari, Mazandaran, 48166-13485, Iran.
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Li X, Li X, Jiang M, Tian W, Zhou B. Single Nucleotide Polymorphisms in PLCE1 for Cancer Risk of Different Types: A Meta-Analysis. Front Oncol 2018; 8:613. [PMID: 30619753 PMCID: PMC6297376 DOI: 10.3389/fonc.2018.00613] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/14/2018] [Accepted: 11/29/2018] [Indexed: 12/27/2022] Open
Abstract
Background: Recent studies have investigated the relationships between PLCE1 polymorphisms and cancer susceptibility. However, some findings lack consistency. Objectives: In the current study, we conducted a meta-analysis to more accurately evaluate the relationships between PLCE1 (rs2274223, rs3765524, rs753724, rs11187842, and rs7922612) single nucleotide polymorphisms (SNPs) and risk for different types of cancer. Methods: We performed a comprehensive search strategy in PubMed, Web of Science, Medline, EMbase, and Scopus for articles available until 19 March 2018. A total of 54 case-control studies comprising 17,955 cases and 20,400 controls were included in the current meta-analysis, which together comprised a total of 32 publications. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate relationships between the PLCE1 polymorphisms and cancer susceptibility. All statistical analyses were performed using Stata 11 software. Results: Results of the meta-analysis demonstrated that the rs2274223 polymorphism showed a significant correlation with increased overall cancer susceptibility (AG vs. AA: OR 1.168, 95% CI 1.084–1.259; GG vs. AA: OR 1.351, 95% CI 1.163–1.570; AG+GG vs. AA: OR 1.193, 95% CI 1.103–1.290; GG vs. AA+AG: OR 1.262, 95% CI 1.102–1.446; G vs. A: OR 1.163, 95% CI 1.089–1.242). Results of subgroup analysis showed that the rs2274223 polymorphism was associated with higher risk for esophageal cancer and gastric cancer relative to colorectal cancer and head and neck cancer. In addition, the rs2274223 polymorphism was found to be associated with increased cancer risk, especially among the subgroups comprising Asians, studies with population-based controls, studies employing the TaqMan genotyping method, and studies consistent with Hardy-Weinberg equilibrium (HWE). The association between the rs3765524 polymorphism and reduced overall cancer risk was detected in one specific genetic model (CT vs. CC: OR 0.681, 95% CI 0.523–0.886). Results of subgroup analysis showed that the rs3765524 polymorphism was associated with cancer risk in a specific genetic model among the subgroups of colorectal cancer, esophageal cancer, Asians, studies with population-based controls, and studies consistent with HWE. However, relationships among the PLCE1 rs753724, rs11187842, and rs7922612 polymorphisms and tumor risk were not identified. Conclusions: Results of the current meta-analysis suggested that PLCE1 (rs2274223, rs3765524) polymorphisms are associated with cancer susceptibility.
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Affiliation(s)
- Xiaoying Li
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.,Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Department of Education, China Medical University, Liaoning, China
| | - Xuelian Li
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.,Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Department of Education, China Medical University, Liaoning, China
| | - Min Jiang
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.,Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Department of Education, China Medical University, Liaoning, China
| | - Wen Tian
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.,Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Department of Education, China Medical University, Liaoning, China
| | - Baosen Zhou
- Department of Epidemiology, School of Public Health, China Medical University, Shenyang, China.,Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Department of Education, China Medical University, Liaoning, China
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Liu Y, Xu Y, Wang Y, Yao Y, Yang J. Associations between interleukin gene polymorphisms and the risk of gastric cancer: A meta-analysis. Clin Exp Pharmacol Physiol 2018; 45:1236-1244. [PMID: 30071135 DOI: 10.1111/1440-1681.13021] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/29/2018] [Accepted: 07/03/2018] [Indexed: 12/15/2022]
Abstract
Recently, the roles of interleukin-2 (IL-2), IL-4, IL-6 and IL-8 gene polymorphisms in gastric cancer (GC) have been studied extensively, with conflicting results. Therefore, we conducted the present meta-analyses to better elucidate the roles of interleukin gene polymorphisms in GC. Eligible articles were searched in PubMed, MEDLINE, Embase, Web of Science and CNKI. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to detect any potential association between interleukin gene polymorphisms and the risk of GC. A total of 63 case-control studies was finally included in our analyses. Significant associations with the risk of GC were detected for the IL-6 rs1800796 and IL-8 rs4073 polymorphisms in overall analyses. Further subgroup analyses based on ethnicities of participants revealed that the IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms were significantly associated with the risk of GC in Asians. Moreover, IL-8 rs4073 polymorphism was also significantly associated with the risk of GC in Africans. In conclusion, our findings suggested that IL-4 rs2243250, IL-6 rs1800796 and IL-8 rs4073 polymorphisms may serve as genetic biomarkers of GC.
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Affiliation(s)
- Yunxia Liu
- Department of Oncology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, Hangzhou, China
| | - Yefeng Xu
- Department of Oncology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, Hangzhou, China
| | - Yiqing Wang
- Department of Oncology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, Hangzhou, China
| | - Yongwei Yao
- Department of Oncology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, Hangzhou, China
| | - Jiewen Yang
- Department of Oncology, Third Hospital of Hangzhou, Affiliated Hangzhou Clinical College, Anhui Medical University, Hangzhou, China
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8
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Wang X, Yang F, Xu G, Zhong S. The roles of IL-6, IL-8 and IL-10 gene polymorphisms in gastric cancer: A meta-analysis. Cytokine 2018; 111:230-236. [DOI: 10.1016/j.cyto.2018.08.024] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 07/30/2018] [Accepted: 08/22/2018] [Indexed: 12/12/2022]
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9
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Park B, Yang S, Lee J, Woo HD, Choi IJ, Kim YW, Ryu KW, Kim YI, Kim J. Genome-Wide Association of Genetic Variation in the PSCA Gene with Gastric Cancer Susceptibility in a Korean Population. Cancer Res Treat 2018; 51:748-757. [PMID: 30189721 PMCID: PMC6473284 DOI: 10.4143/crt.2018.162] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 09/04/2018] [Indexed: 12/29/2022] Open
Abstract
PURPOSE Half of the world's gastric cancer cases and the highest gastric cancer mortality rates are observed in Eastern Asia. Although several genome-wide association studies (GWASs) have revealed susceptibility genes associated with gastric cancer, no GWASs have been conducted in the Korean population, which has the highest incidence of gastric cancer. Materials and Methods We performed genome scanning of 450 gastric cancer cases and 1,134 controls via Affymetrix Axiom Exome 319 arrays, followed by replication of 803 gastric cancer cases and 3,693 healthy controls. RESULTS We showed that the rs2976394 in the prostate stem cell antigen (PSCA) gene is a gastriccancer-susceptibility gene in a Korean population, with genome-wide significance and an odds ratio (OR) of 0.70 (95% confidence interval [CI], 0.64 to 0.77). A strong linkage disequilibrium with rs2294008 was also found, indicating an association with susceptibility. Individuals with the CC genotype of the PSCA gene showed an approximately 2-fold lower risk of gastric cancer compared to those with the TT genotype (OR, 0.47; 95% CI, 0.39 to 0.57). The effect of the PSCA gene on gastric cancer was more prominent in the female population and for diffuse type gastric cancer. CONCLUSION Our result confirmed that the PSCA gene may be the most important susceptibility gene for gastric cancer risk in a Korean population.
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Affiliation(s)
- Boyoung Park
- Department of Medicine, Hanyang University College of Medicine, Seoul, Korea.,Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea
| | - Sarah Yang
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea.,Department of Public Health, Graduate School of Public Health, Seoul National University, Seoul, Korea
| | - Jeonghee Lee
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea
| | - Hae Dong Woo
- Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea
| | - Il Ju Choi
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Young Woo Kim
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Keun Won Ryu
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Young-Il Kim
- Center for Gastric Cancer, National Cancer Center Hospital, National Cancer Center, Goyang, Korea
| | - Jeongseon Kim
- Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Korea.,Molecular Epidemiology Branch, Division of Cancer Epidemiology and Prevention, Research Institute, National Cancer Center, Goyang, Korea
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MUC1, MUC5AC, and MUC6 polymorphisms, Helicobacter pylori infection, and gastric cancer: a systematic review and meta-analysis. Eur J Cancer Prev 2018; 27:323-330. [DOI: 10.1097/cej.0000000000000348] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Liao X, Han C, Qin W, Liu X, Yu L, Zhu G, Yu T, Lu S, Su H, Liu Z, Chen Z, Yang C, Huang K, Liu Z, Liang Y, Huang J, Dong J, Li L, Qin X, Ye X, Xiao K, Peng M, Peng T. PLCE1 polymorphisms and expression combined with serum AFP level predicts survival of HBV-related hepatocellular carcinoma patients after hepatectomy. Oncotarget 2018; 8:29202-29219. [PMID: 28418898 PMCID: PMC5438724 DOI: 10.18632/oncotarget.16346] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2016] [Accepted: 02/22/2017] [Indexed: 12/17/2022] Open
Abstract
Polymorphisms in the phospholipase C epsilon (PLCE) 1 gene play a crucial role in the development and progression of several types of cancer. The present study investigated the prognostic significance of PLCE1 gene polymorphisms and expression combined with serum α-fetoprotein (AFP) level in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC). Single nucleotide polymorphisms were genotyped by sequencing DNA isolated from surgically resected tumor samples of 421 HBV-related HCC patients, and expression profiles were generated based on the GSE14520 dataset. A joint-effects analysis of PLCE1 haplotypes (Ars2274223Crs3765524; Grs2274223Trs3765524) with AFP level stratified at 20 ng/ml showed a significant association with overall survival(OS) of HBV-related HCC patients(log-rank P=0.0003). Patients with AC and GT haplotypes with AFP level ≥ 20 ng/ml had an increased risk of death as compared to those with the AC haplotype and AFP level < 20 ng/ml (adjusted P=0.029 and 0.041, respectively). Patients with the GT haplotype and AFP level < 20 ng/ml also had an increased risk of death, although with a non-significant P value (adjusted P=0.092). Joint-effects analysis of PLCE1 mRNA expression with serum AFP level stratified at 300 ng/ml was significantly associated with HBV-related HCC recurrence and OS. Our results demonstrate that PLCE1 haplotypes (including rs2274223 and rs3765524) and expression combined with serum AFP level may predict postoperative outcome of HBV-related HCC patients.
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Affiliation(s)
- Xiwen Liao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Chuangye Han
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Wei Qin
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Xiaoguang Liu
- Department of Hepatobiliary Surgery, Affiliated Hospital of Guangdong Medical University, Zhanjiang, 524001, Guangdong Province, China
| | - Long Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, Henan Province, China
| | - Guangzhi Zhu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Tingdong Yu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Sicong Lu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Hao Su
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhen Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhiwei Chen
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Chengkun Yang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Ketuan Huang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Zhengtao Liu
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Yu Liang
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Jianlu Huang
- Department of Hepatobiliary Surgery, The Third Affiliated Hospital of Guangxi Medical University, Nanning 530031, Guangxi Province, China
| | - Jiahong Dong
- Department of Hepato-Biliary-Pancreatic Surgery, Beijing Tsinghua Changgung Hospital, Beijing, 102218, China
| | - Lequn Li
- Department of Hepatobiliary Surgery, Affiliated Tumor Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Xue Qin
- Department of Clinical Laboratory, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi Province, China
| | - Xinping Ye
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Kaiyin Xiao
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Minhao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
| | - Tao Peng
- Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, Guangxi Province, China
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12
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Liu X, Li Z, Song Y, Wang R, Han L, Wang Q, Jiang K, Kang C, Zhang Q. AURKA induces EMT by regulating histone modification through Wnt/β-catenin and PI3K/Akt signaling pathway in gastric cancer. Oncotarget 2018; 7:33152-64. [PMID: 27121204 PMCID: PMC5078082 DOI: 10.18632/oncotarget.8888] [Citation(s) in RCA: 83] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Accepted: 03/28/2016] [Indexed: 12/31/2022] Open
Abstract
Gastric cancer, a highly invasive and aggressive malignancy, is the third leading cause of death from cancer worldwide. Genetic association studies have successfully revealed several important genes consistently associated with gastric cancer to date. However, these robust gastric cancer-associated genes do not fully elucidate the mechanisms underlying the development and progression of the disease. In the present study, we performed an alternative approach, a gene expression-based genome-wide association study (eGWAS) across 13 independent microarray experiments (including 251 gastric cancer cases and 428 controls), to identify top candidates (p<0.00001). Additionally, we conducted gene ontology analysis, pathway analysis and network analysis and identified aurora kinase A (AURKA) as our candidate. We observed that MLN8237, which is a specific inhibitor of AURKA, decreased the β-catenin and the phosphorylation of Akt1 and GSK-3β, as well as blocked the Akt and Wnt signaling pathways. Furthermore, MLN8237 arrested the cells in the G2/M phase. The activity of Wnt and Akt signaling pathways affected the level of histone methylation significantly, and we supposed that MLN8237 affected the level of histone methylation through these two signaling pathways. Additionally, the treatment of MLN8237 influenced the level of H3K4 me1/2/3 and H3K27 me1/2/3. Chip data on cell lines suggested that MLN8237 increases the level of H3K27 me3 on the promoter of Twist and inhibits EMT (epithelial-mesenchymal transition). In summary, AURKA is a potential therapeutic target in gastric cancer and induces EMT through histone methylation.
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Affiliation(s)
- Xi Liu
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Zhaoxia Li
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Yue Song
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Rui Wang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Lei Han
- Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China
| | - Qixue Wang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, China.,Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China
| | - Kui Jiang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
| | - Chunsheng Kang
- Department of Neurosurgery, Tianjin Medical University General Hospital, Heping District, Tianjin 300052, China.,Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, China
| | - Qingyu Zhang
- Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, China
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13
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Gu Y, Deng B, Kong J, Yan C, Huang T, Yang J, Wang Y, Wang T, Qi Q, Jin G, Du J, Ding Y, Liu L. Functional polymorphisms in NR3C1 are associated with gastric cancer risk in Chinese population. Oncotarget 2017; 8:105312-105319. [PMID: 29285253 PMCID: PMC5739640 DOI: 10.18632/oncotarget.22172] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2017] [Accepted: 09/20/2017] [Indexed: 02/05/2023] Open
Abstract
Recently promoter of NR3C1 has been found to be high methylated in gastric cancer tissues which might be involved in the initiation of gastric carcinoma development. To test whether the variants in NR3C1 could modify the risk of gastric cancer, we evaluated the association between four SNPs (rs6194, rs12521436, rs33388 and rs4912913) in NR3C1 and gastric cancer risk in a case-control study with 1,113 gastric cancer cases and 1,848 cancer-free controls in a Chinese population. We found a significant association between rs4912913 and gastric cancer risk (OR=1.18, 95%CI=1.05-1.33, P=5.49×10-3). We also observed that the A-allele of rs12521436 and rs33388 were significantly associated with a decreased risk of gastric cancer (OR=0.84, 95%CI=0.76-0.94, P=2.78×10-3; OR=0.85, 95%CI=0.75-0.97; P=0.018). Finally, we made a joint effect analysis of rs12521436, rs33388 and rs4912913 on risk of gastric cancer (PTrend =2.83×10-5). These findings indicate that the variants rs4912913, rs33388 and rs12521436 of NR3C1 may contribute to gastric cancer susceptibility.
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Affiliation(s)
- Yayun Gu
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Bin Deng
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Jing Kong
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Caiwang Yan
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Tongtong Huang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Jianshui Yang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Yan Wang
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital, Nanjing, China
| | - Tianpei Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Qi Qi
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Guangfu Jin
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Jiangbo Du
- Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
| | - Yanbing Ding
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou, China
| | - Li Liu
- Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, Nanjing Medical University, Nanjing, China
- Digestive Endoscopy Center, The First Affiliated Hospital of Nanjing Medical University and Jiangsu Province Hospital, Nanjing, China
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14
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Ye Y, Yang C, Xu L, Fang D. MUC1 rs4072037 polymorphism is associated with decreased risk of gastric cancer: a meta-analysis. Int J Biol Markers 2017; 32:e284-e290. [PMID: 28561882 DOI: 10.5301/ijbm.5000270] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 04/06/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Several studies have recently investigated the association between mucin 1 (MUC1) rs4072037 polymorphism and gastric cancer (GC) risk, but with conflicting results. The aim of this meta-analysis was to evaluate the association between MUC1 rs4072037 polymorphism and GC risk. METHODS A comprehensive database search of PubMed, Elsevier, Embase and China National Knowledge Infrastructure (CNKI) databases was performed to identify relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of any association. RESULTS A total of 12 papers containing 18 studies were included in this meta-analysis, involving 12,373 cases and 15,008 controls. Our data suggested that rs4072037 polymorphism was associated with a decreased risk of GC. Stratification analyses of ethnicity indicated that rs4072037 decreased the risk of GC among white populations, but no significant relationship was observed among Asian populations. No significant associations were observed in subgroups of Lauren classification (intestinal or diffuse) and anatomical classification (cardia or non-cardia). CONCLUSIONS In conclusion, this meta-analysis suggested that rs4245739 polymorphism in the MUC1 gene may play a pivotal role in the pathogenesis of GC, especially for white populations.
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Affiliation(s)
- Yu Ye
- Department of General Surgery, Hang Zhou Red Cross Hospital, Hangzhou, Zhejiang - PR China
| | - Chong Yang
- Department of General Surgery, Hang Zhou Red Cross Hospital, Hangzhou, Zhejiang - PR China
| | - Lei Xu
- Department of Digestion, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang - PR China
| | - Dilong Fang
- Department of General Surgery, Hang Zhou Red Cross Hospital, Hangzhou, Zhejiang - PR China
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15
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Gigek CO, Calcagno DQ, Rasmussen LT, Santos LC, Leal MF, Wisnieski F, Burbano RR, Lourenço LG, Lopes-Filho GJ, Smith MAC. Genetic variants in gastric cancer: Risks and clinical implications. Exp Mol Pathol 2017; 103:101-111. [PMID: 28736214 DOI: 10.1016/j.yexmp.2017.07.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2017] [Revised: 07/03/2017] [Accepted: 07/19/2017] [Indexed: 12/14/2022]
Abstract
Cancer is a multifactorial disease that involves many molecular alterations. Gastric cancer (GC) is the third leading cause of cancer death worldwide. GC is a highly heterogeneous disease with different molecular and genetics features. Therefore, this review focuses on an overview of the genetic aspects of gastric cancer by highlighting the important impact and role of deletions and/or duplications of chromosomal segments, genomic variants, H. pylori infection and interleukin variants, as found in gene expression and newly proposed molecular classification studies. The challenge is to better understand the mechanisms and different pathways that lead to the development and progression of GC.
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Affiliation(s)
- Carolina Oliveira Gigek
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil; Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil.
| | - Danielle Queiroz Calcagno
- Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará (UFPA), CEP: 66073-000 Belém, Pará, Brazil
| | | | - Leonardo Caires Santos
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
| | - Mariana Ferreira Leal
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil; Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo (UNIFESP), CEP 04038-032 São Paulo, Brazil
| | - Fernanda Wisnieski
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
| | | | - Laercio Gomes Lourenço
- Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil
| | - Gaspar Jesus Lopes-Filho
- Disciplina de Gastroenterologia Cirúrgica, Universidade Federal de São Paulo (UNIFESP), CEP: 04024-002 São Paulo, Brazil
| | - Marilia Arruda Cardoso Smith
- Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), CEP 04023-900 São Paulo, Brazil
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16
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Wang Z, Dai J, Hu N, Miao X, Abnet CC, Yang M, Freedman ND, Chen J, Burdette L, Zhu X, Chung CC, Ren C, Dawsey SM, Wang M, Ding T, Du J, Gao YT, Zhong R, Giffen C, Pan W, Koh WP, Dai N, Liao LM, Yan C, Qiao YL, Jiang Y, Shu XO, Chen J, Wang C, Ma H, Su H, Zhang Z, Wang L, Wu C, Xiang YB, Hu Z, Yuan JM, Xie L, Zheng W, Lin D, Chanock SJ, Shi Y, Goldstein AM, Jin G, Taylor PR, Shen H. Identification of new susceptibility loci for gastric non-cardia adenocarcinoma: pooled results from two Chinese genome-wide association studies. Gut 2017; 66:581-587. [PMID: 26701879 PMCID: PMC4963301 DOI: 10.1136/gutjnl-2015-310612] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 11/01/2015] [Accepted: 11/17/2015] [Indexed: 01/29/2023]
Abstract
OBJECTIVE Although several genome-wide association studies (GWAS) of non-cardia gastric cancer have been published, more novel association signals could be exploited by combining individual studies together, which will further elucidate the genetic susceptibility of non-cardia gastric cancer. DESIGN We conducted a meta-analysis of two published Chinese GWAS studies (2031 non-cardia gastric cancer cases and 4970 cancer-free controls) and followed by genotyping of additional 3564 cases and 4637 controls in two stages. RESULTS The overall meta-analysis revealed two new association signals. The first was a novel locus at 5q14.3 and marked by rs7712641 (per-allele OR=0.84, 95% CI 0.80 to 0.88; p=1.21×10-11). This single-nucleotide polymorphism (SNP) marker maps to the intron of the long non-coding RNA, lnc-POLR3G-4 (XLOC_004464), which we observed has lower expression in non-cardia gastric tumour compared with matched normal tissue (Pwilcoxon signed-rank=7.20×10-4). We also identified a new signal at the 1q22 locus, rs80142782 (per-allele OR=0.62; 95% CI 0.56 to 0.69; p=1.71×10-19), which was independent of the previously reported SNP at the same locus, rs4072037 (per-allele OR=0.74; 95% CI 0.69 to 0.79; p=6.28×10-17). Analysis of the new SNP conditioned on the known SNP showed that the new SNP remained genome-wide significant (Pconditional=3.47×10-8). Interestingly, rs80142782 has a minor allele frequency of 0.05 in East Asians but is monomorphic in both European and African populations. CONCLUSION These findings add new evidence for inherited genetic susceptibility to non-cardia gastric cancer and provide further clues to its aetiology in the Han Chinese population.
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Affiliation(s)
- Zhaoming Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA,Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, Maryland, USA,Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Juncheng Dai
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Nan Hu
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Xiaoping Miao
- Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Christian C Abnet
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Ming Yang
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, People's Republic of China
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Jinfei Chen
- Department of Oncology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People's Republic of China
| | - Laurie Burdette
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA,Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, Maryland, USA
| | - Xun Zhu
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Charles C Chung
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA,Cancer Genomics Research Laboratory, Leidos Biomedical Research Inc., Gaithersburg, Maryland, USA
| | - Chuanli Ren
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China,Clinical Medical Testing Laboratory, Northern Jiangsu People's Hospital and Clinical Medical College of Yangzhou University, Yangzhou, People's Republic of China
| | - Sanford M Dawsey
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Meilin Wang
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Ti Ding
- Shanxi Cancer Hospital, Taiyuan, Shanxi, P.R. China
| | - Jiangbo Du
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Yu-Tang Gao
- Shanghai Cancer Institute, Shanghai, People's Republic of China
| | - Rong Zhong
- Department of Epidemiology and Biostatistics, and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People's Republic of China
| | - Carol Giffen
- Information Management Services Inc., Silver Spring, Maryland, USA
| | - Wenting Pan
- State Key Laboratory of Chemical Resource Engineering, Beijing Laboratory of Biomedical Materials, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, People's Republic of China
| | - Woon-Puay Koh
- Duke-NUS Graduate Medical School Singapore, and Saw Swee Hock School of Public Health, National University of Singapore, Singapore
| | - Ningbing Dai
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Linda M Liao
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Caiwang Yan
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - You-Lin Qiao
- Department of Epidemiology, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yue Jiang
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Xiao-Ou Shu
- Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
| | - Jiaping Chen
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Chaoyu Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hongxia Ma
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Hua Su
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Zhendong Zhang
- Department of Genetic Toxicology, the Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Lemin Wang
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Chen Wu
- Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Yong-Bing Xiang
- Shanghai Cancer Institute, Shanghai, People's Republic of China
| | - Zhibin Hu
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Jian-Min Yuan
- Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute; Pittsburgh, Pennsylvania, USA,Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Lu Xie
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Wei Zheng
- Department of Medicine and Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee, USA
| | - Dongxin Lin
- Department of Etiology & Carcinogenesis, Cancer Institute and Hospital Chinese Academy of Medical Sciences, Beijing, People's Republic of China
| | - Stephen J Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Yongyong Shi
- Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Bio-X Institutes, Shanghai Jiao Tong University, Shanghai, People's Republic of China
| | - Alisa M Goldstein
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Guangfu Jin
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
| | - Philip R Taylor
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
| | - Hongbing Shen
- Department of Epidemiology and Biostatistics, Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Medicine, School of Public Health, Nanjing Medical University, Nanjing, People's Republic of China
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17
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Tyutyunnykova A, Telegeev G, Dubrovska A. The controversial role of phospholipase C epsilon (PLCε) in cancer development and progression. J Cancer 2017; 8:716-729. [PMID: 28382133 PMCID: PMC5381159 DOI: 10.7150/jca.17779] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2016] [Accepted: 12/23/2016] [Indexed: 01/21/2023] Open
Abstract
The phospholipase C (PLC) enzymes are important regulators of membrane phospholipid metabolism. PLC proteins can be activated by the receptor tyrosine kinases (RTK) or G-protein coupled receptors (GPCR) in response to the different extracellular stimuli including hormones and growth factors. Activated PLC enzymes hydrolyze phosphoinositides to increase the intracellular level of Ca2+ and produce diacylglycerol, which are important mediators of the intracellular signaling transduction. PLC family includes 13 isozymes belonging to 6 subfamilies according to their domain structures and functions. Although importance of PLC enzymes for key cellular functions is well established, the PLC proteins belonging to the ε, ζ and η subfamilies were identified and characterized only during the last decade. As a largest known PLC protein, PLCε is involved in a variety of signaling pathways and controls different cellular properties. Nevertheless, its role in carcinogenesis remains elusive. The aim of this review is to provide a comprehensive and up-to-date overview of the experimental and clinical data about the role of PLCε in the development and progression of the different types of human and experimental tumors.
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Affiliation(s)
- Anna Tyutyunnykova
- OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, 01307 Dresden, Germany
| | - Gennady Telegeev
- The Institute of Molecular Biology and Genetics of NASU, Kyiv, Ukraine
| | - Anna Dubrovska
- OncoRay - National Center for Radiation Research in Oncology, Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universität Dresden and Helmholtz-Zentrum Dresden-Rossendorf, Fetscherstrasse 74, 01307 Dresden, Germany.; German Cancer Consortium (DKTK), Dresden, Germany.; Deutsches Krebsforschungszentrum (DKFZ), Heidelberg, Germany
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18
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Liu P, Gao ZH, Ma JC, Yang J, Zhang YB, Yan HL, Yao JB, Da MX. Association between MUC1 rs4072037 polymorphism and susceptibility to gastric cancer: A meta-analysis based on ten case-control trials. Shijie Huaren Xiaohua Zazhi 2016; 24:4576-4583. [DOI: 10.11569/wcjd.v24.i34.4576] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate the association between the MUC1 rs4072037 polymorphism and susceptibility to gastric cancer (GC) by conducting a meta-analysis.
METHODS PubMed, Embase, The Cochrane Library, CBM, CNKI, VIP and WanFang Database were searched for published case-control studies investigating the relationship between the MUC1 rs4072037 polymorphism and susceptibility to GC. Data were extracted and cross-checked from the case-control studies by two independent reviewers. Statistical analysis and heterogeneity test were conducted with Stata12.0.
RESULTS Ten case-control studies including 10700 GC patients and 12891 controls were analyzed in this meta-analysis. Results indicated that allele model (A vs G: OR = 1.42, 95%CI: 1.29-1.56, P < 0.001), dominant model (AA + AG vs GG: OR = 1.40, 95%CI: 1.21-1.61, P < 0.001), co-dominant model (AA vs GG: OR = 1.78, 95%CI: 1.52-2.08, P < 0.001), and recessive model (AA vs AG+GG: OR = 1.56, 95%CI: 1.38-1.76, P < 0.001) were strongly associated with the risk of GC. Subgroup analysis showed that allele model (A vs G: OR = 1.39, 95%CI: 1.21-1.60), dominant model (AA vs GG: OR = 2.01, 95%CI: 1.51-2.66)and co-dominant model (AA vs AG+GG: OR = 1.63, 95%CI: 1.29-2.07) increased the risk of GC in Caucasians.
CONCLUSION The MUC1 rs4072037 polymorphism is closely associated with the susceptibility to GC, and the allele A increases the risk of GC. MUC1 rs4072037 polymorphism may be used as a potential biomarker for GC.
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Qiu LX, Hua RX, Cheng L, He J, Wang MY, Zhou F, Zhu XD, Sun MH, Zhou XY, Li J, Wang YN, Yang YJ, Wang JC, Jin L, Guo WJ, Wei QY. Genetic variant rs4072037 of MUC1 and gastric cancer risk in an Eastern Chinese population. Oncotarget 2016; 7:15930-15936. [PMID: 26910281 PMCID: PMC4941287 DOI: 10.18632/oncotarget.7527] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2015] [Accepted: 12/31/1969] [Indexed: 02/07/2023] Open
Abstract
Published data on the association between the MUC1 rs4072037A > G polymorphism and gastric cancer (GCa) risk were inconclusive. To derive a more precise estimation of the association, we conducted a large GCa study of 1,124 cases and 1,192 controls to confirm this association in an Eastern Chinese population. Our results showed that the G allele was strongly associated with a decreased GCa risk in the study population [GG vs. AA, odds ratio (OR) = 0.47, 95% confidence interval (CI) = 0.31-0.73; AG/GG vs. AA, OR = 0.82, 95% CI = 0.68-0.99; GG vs. AA/AG, OR = 0.48, 95% CI = 0.32-0.74]. These associations remained significant in subgroups of age, tumor site, drinking and smoking status. Moreover, this association was supported by an additional meta-analysis of published studies. In summary, these results suggest that the MUC1 rs4072037G allele may be a low-penetrating protection factor for GCa risk in Chinese populations.
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Affiliation(s)
- Li-Xin Qiu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Rui-Xi Hua
- Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China
| | - Lei Cheng
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jing He
- Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, Guangdong, China
| | - Meng-Yun Wang
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Fei Zhou
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiao-Dong Zhu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Meng-Hong Sun
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Xiao-Yan Zhou
- Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Ya-Nong Wang
- Department of Gastric Cancer and Soft Tissue Sarcoma Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
| | - Ya-Jun Yang
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Jiu-Cun Wang
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Li Jin
- Ministry of Education Key Laboratory of Contemporary Anthropology and State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, China
- Fudan-Taizhou Institute of Health Sciences, Taizhou, Jiangsu, China
| | - Wei-Jian Guo
- Department of Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Qing-Yi Wei
- Cancer Institute, Collaborative Innovation Center for Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, China
- Duke Cancer Institute, Duke University Medical Center and Department of Medicine, Duke University School of Medicine, Durham, NC, USA
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Xue W, Zhu M, Wang Y, He J, Zheng L. Association between PLCE1 rs2274223 A > G polymorphism and cancer risk: proof from a meta-analysis. Sci Rep 2015; 5:7986. [PMID: 25614244 PMCID: PMC4303865 DOI: 10.1038/srep07986] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 12/24/2014] [Indexed: 02/07/2023] Open
Abstract
UNLABELLED Phospholipase C epsilon 1 (PLCE1) plays an important role in cell growth, differentiation and oncogenesis. An increasing number of individual studies have investigated the association between PLCE1 rs2274223 polymorphism and cancer risk, but the conclusions are inconclusive. To obtain a comprehensive conclusion, we performed a meta-analysis of 22 studies with 13188 cases and 14666 controls. The pooled results indicated that PLCE1 rs2274223 A > G polymorphism was associated with an increased risk of overall cancer (G vs. A: OR = 1.15, 95% CI = 1.06-1.25; GG vs. AA: OR = 1.30, 95% CI = 1.10-1.55; GA vs. AA: OR = 1.18, 95% CI = 1.08-1.30; GG/GA vs. AA: OR = 1.20, 95% CI = 1.08-1.32; GG vs. GA/AA OR = 1.22, 95% CI = 1.04-1.42). The stratification analysis showed the polymorphism was significantly associated with an increased risk of esophageal squamous cell carcinoma (ESCC) other than gastric cancer (GC), especially among the subgroups of Asian, high quality score, sample size > 1000 and the studies consistent with Hardy-Weinberg equilibrium (HWE). This meta-analysis demonstrated that PLCE1 rs2274223 A > G polymorphism may be associated with increased susceptibility to cancer, especially for ESCC. However, due to the substantial heterogeneities across the studies, the conclusion might be not conclusive that need more studies to confirm.
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Affiliation(s)
- Wenji Xue
- Department of Oncology, Xin Hua Hospital affiliated To Shanghai Jiaotong University School of Medicine, Shanghai 200092, Shanghai, China
| | - Meiling Zhu
- Department of Oncology, Xin Hua Hospital affiliated To Shanghai Jiaotong University School of Medicine, Shanghai 200092, Shanghai, China
| | - Yiwei Wang
- Department of Oncology, Xin Hua Hospital affiliated To Shanghai Jiaotong University School of Medicine, Shanghai 200092, Shanghai, China
| | - Jing He
- State Key Laboratory of Oncology in South China, Department of Experimental Research, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, Guangdong, China
| | - Leizhen Zheng
- Department of Oncology, Xin Hua Hospital affiliated To Shanghai Jiaotong University School of Medicine, Shanghai 200092, Shanghai, China
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Abstract
Gastric cancer remains highly prevalent and accounts for a notable proportion of global cancer mortality. This cancer is also associated with poor survival rates. Understanding the genetic basis of gastric cancer will offer insights into its pathogenesis, help identify new biomarkers and novel treatment targets, aid prognostication and could be central to developing individualized treatment strategies in the future. An inherited component contributes to <3% of gastric cancers; the majority of genetic changes associated with gastric cancer are acquired. Over the past few decades, advances in technology and high-throughput analysis have improved understanding of the molecular aspects of the pathogenesis of gastric cancer. These aspects are multifaceted and heterogeneous and represent a wide spectrum of several key genetic influences, such as chromosomal instability, microsatellite instability, changes in microRNA profile, somatic gene mutations or functional single nucleotide polymorphisms. These genetic aspects of the pathogenesis of gastric cancer will be addressed in this Review.
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Affiliation(s)
- Mairi H McLean
- National Cancer Institute, Laboratory of Molecular Immunoregulation, Cancer &Inflammation Program, 1050 Boyles Street, Frederick, MD 21702-1201, USA
| | - Emad M El-Omar
- Division of Applied Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB51 5ER, UK
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Liu X, Wang Z, Zhang X, Chang J, Tang W, Gan L, Wu Z, Li J. MUC1 gene polymorphism rs4072037 and susceptibility to gastric cancer: a meta-analysis. SPRINGERPLUS 2014; 3:599. [PMID: 25332893 PMCID: PMC4198476 DOI: 10.1186/2193-1801-3-599] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/04/2014] [Accepted: 10/06/2014] [Indexed: 12/14/2022]
Abstract
The association between MUC1 polymorphism rs4072037 and the risk of gastric cancer has been described in several studies. However, these studies yielded inconsistent results, especially in different pathological type of gastric cancer. Therefore, we performed this meta-analysis to evaluate the relationship between MUC1 gene polymorphism and gastric cancer susceptibility. A comprehensive database search was performed to identify eligible studies. Odds ratios with 95% confidence intervals were calculated to assess the strength of the association between MUC1 rs4072037 and risk of gastric cancer. Subgroup analyses, publication bias, and sensitivity analyses were also conducted. PubMed, EMBASE, Web of Science and CNKI databases were systematically searched to identify relevant studies. A total of 9 studies (12 datasets) were included in the meta-analysis including 10,410 cases and 11,437 controls. Overall, the G allele at rs4072037 of MUC1 gene was associated with a significant decreased gastric cancer risk (OR=0.70, 95% CI: 0.64-0.76). The association was significant in both anatomic location and pathological subtype subgroup analyses. However, the association was detected in Asian rather than Caucasian. Our findings demonstrate that the presence of the G allele at rs4072037 of the MUC1 gene may contribute to protection against gastric cancer in Asian. Further large studies of multiethnic groups are needed to validate these findings.
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Affiliation(s)
- Xinyang Liu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Zhichao Wang
- Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, 200032 China
| | - Xiaowei Zhang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Jinjia Chang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Wenbo Tang
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Lu Gan
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Zheng Wu
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
| | - Jin Li
- Department of Medical Oncology, Fudan University Shanghai Cancer Center; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032 PR China
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Saeki N, Sakamoto H, Yoshida T. Mucin 1 gene (MUC1) and gastric-cancer susceptibility. Int J Mol Sci 2014; 15:7958-73. [PMID: 24810688 PMCID: PMC4057712 DOI: 10.3390/ijms15057958] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/03/2014] [Revised: 04/11/2014] [Accepted: 04/21/2014] [Indexed: 12/22/2022] Open
Abstract
Gastric cancer (GC) is one of the major malignant diseases worldwide, especially in Asia. It is classified into intestinal and diffuse types. While the intestinal-type GC (IGC) is almost certainly caused by Helicobacter pylori (HP) infection, its role in the diffuse-type GC (DGC) appears limited. Recently, genome-wide association studies (GWAS) on Japanese and Chinese populations identified chromosome 1q22 as a GC susceptibility locus which harbors mucin 1 gene (MUC1) encoding a cell membrane-bound mucin protein. MUC1 has been known as an oncogene with an anti-apoptotic function in cancer cells; however, in normal gastric mucosa, it is anticipated that the mucin 1 protein has a role in protecting gastric epithelial cells from a variety of external insults which cause inflammation and carcinogenesis. HP infection is the most definite insult leading to GC, and a protective function of mucin 1 protein has been suggested by studies on Muc1 knocked-out mice.
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Affiliation(s)
- Norihisa Saeki
- Division of Genetics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
| | - Hiromi Sakamoto
- Division of Genetics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
| | - Teruhiko Yoshida
- Division of Genetics, National Cancer Center Research Institute, Tsukiji 5-1-1, Chuo-ku, Tokyo 104-0045, Japan.
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Kim J, Kim Y, Lee KA. Ethnic differences in gastric cancer genetic susceptibility: allele flips of interleukin gene. World J Gastroenterol 2014; 20:4558-4565. [PMID: 24782608 PMCID: PMC4000492 DOI: 10.3748/wjg.v20.i16.4558] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 12/12/2013] [Accepted: 03/08/2014] [Indexed: 02/06/2023] Open
Abstract
Polymorphisms in promoter regions of inflammatory cytokines have been widely studied, and potentially functional polymorphisms have been discovered. Conflicting results from meta-analyses of interleukin (IL)-1B and IL-10 polymorphisms show differences in gastric cancer susceptibilities between Caucasian and Asian populations. In particular, we note the suggestion of an allele flip in IL-1B and IL-10 gene polymorphisms. In Asian populations, the IL-1B-1464G/-511C/-31T haplotype indicates risk for gastric cancer, while the opposite haplotype, IL-1B-1464C/-511T/-31C is the risk-related allele in Caucasians. Furthermore, while IL-10-1082G/-819C/-592C is associated with gastric cancer in Asians, IL-10-1082A/-819T/-592T is linked to gastric cancer risk in Caucasians. These seemingly contradictory results may be attributed to distinct carcinogenic mechanisms underlying the different gastric cancer subtypes. The allele flip observed in IL-10 and gastric cancer appears to reflect allelic heterogeneity, similar to that observed in IL-1B. In this review, we focus on the allele flip phenomenon observed between different ethnic groups in an effort to resolve certain controversial results from recent studies on interleukin polymorphism. In addition, we re-emphasize the importance of stratifying gastric cancer subtypes based on anatomical site and Lauren classification to prevent false associations arising through dilution of true ones.
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