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Jiang Q, Geng P, Zhang Y, Yang M, Zhu J, Zhang M, Wang Y, Feng Y, Sun X. Associations between CDH1 gene polymorphisms and the risk of gastric cancer: A meta-analysis based on 44 studies. Medicine (Baltimore) 2024; 103:e38244. [PMID: 38847676 PMCID: PMC11155553 DOI: 10.1097/md.0000000000038244] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 04/25/2024] [Indexed: 06/10/2024] Open
Abstract
BACKGROUND Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data. METHODS Relevant case-control studies were collected from PubMed, Embase, Web of Science and Cochrane databases up to January 7, 2024. Subsequently, odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of correlations. A sensitivity analysis was performed to evaluate the robustness and reliability of these included studies. RESULTS A total of 25 articles including 44 studies, were included in this meta-analysis, including 26 studies on rs16260, 6 studies on rs3743674, 7 studies on rs5030625, and 5 studies on rs1801552. The pooled results showed that rs16260 was remarkably associated with an increased GC risk of GC among Caucasians. Moreover, the rs5030625 variation dramatically enhanced GC predisposition in the Asian population. However, no evident correlations between CDH1 rs3743674 and rs1801552 polymorphisms and GC risk were observed. CONCLUSIONS Our findings suggested that CDH1 gene polymorphisms were significantly correlated with GC risk, especially in rs16260 and rs5030625 polymorphisms.
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Affiliation(s)
- Qiqi Jiang
- Department of Gastroenterology, Weifang People’s Hospital, The First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Peizhen Geng
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
| | - Yuying Zhang
- Department of Gastroenterology, Weifang People’s Hospital, The First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Maoquan Yang
- School of Clinical Medicine, Shandong Second Medical University, Weifang, Shandong, China
| | - Jiafeng Zhu
- School of Nursing, Shandong Second Medical University, Weifang, Shandong, China
| | - Mingwei Zhang
- Department of Pathology, Shandong University School of Basic Medical Sciences, Jinan, Shandong, China
| | - Yamei Wang
- Department of Occupational Diseases, Weifang People’s Hospital, The First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Yikuan Feng
- Department of Gastroenterology, Weifang People’s Hospital, The First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
| | - Xiaojuan Sun
- Department of Occupational Diseases, Weifang People’s Hospital, The First Affiliated Hospital of Weifang Medical University, Weifang, Shandong, China
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de Melo IG, Tavares V, Pereira D, Medeiros R. Contribution of Endothelial Dysfunction to Cancer Susceptibility and Progression: A Comprehensive Narrative Review on the Genetic Risk Component. Curr Issues Mol Biol 2024; 46:4845-4873. [PMID: 38785560 PMCID: PMC11120512 DOI: 10.3390/cimb46050292] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2024] [Revised: 05/09/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024] Open
Abstract
Venous thromboembolism (VTE) is a challenging clinical obstacle in oncological settings, marked by elevated incidence rates and resulting morbidity and mortality. In the context of cancer-associated thrombosis (CAT), endothelial dysfunction (ED) plays a crucial role in promoting a pro-thrombotic environment as endothelial cells lose their ability to regulate blood flow and coagulation. Moreover, emerging research suggests that this disorder may not only contribute to CAT but also impact tumorigenesis itself. Indeed, a dysfunctional endothelium may promote resistance to therapy and favour tumour progression and dissemination. While extensive research has elucidated the multifaceted mechanisms of ED pathogenesis, the genetic component remains a focal point of investigation. This comprehensive narrative review thus delves into the genetic landscape of ED and its potential ramifications on cancer progression. A thorough examination of genetic variants, specifically polymorphisms, within key genes involved in ED pathogenesis, namely eNOS, EDN1, ACE, AGT, F2, SELP, SELE, VWF, ICAM1, and VCAM1, was conducted. Overall, these polymorphisms seem to play a context-dependent role, exerting both oncogenic and tumour suppressor effects depending on the tumour and other environmental factors. In-depth studies are needed to uncover the mechanisms connecting these DNA variations to the pathogenesis of malignant diseases.
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Affiliation(s)
- Inês Guerra de Melo
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
| | - Valéria Tavares
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
| | - Deolinda Pereira
- Oncology Department, Portuguese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal;
| | - Rui Medeiros
- Molecular Oncology and Viral Pathology Group, Research Center of IPO Porto (CI-IPOP)/Pathology and Laboratory Medicine Dep., Clinical Pathology SV/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto)/Porto Comprehensive Cancer Centre (Porto. CCC), 4200-072 Porto, Portugal; (I.G.d.M.); (V.T.)
- Faculty of Medicine of University of Porto (FMUP), 4200-072 Porto, Portugal
- ICBAS—Instituto de Ciências Biomédicas Abel Salazar, Universidade do Porto, 4050-313 Porto, Portugal
- Faculty of Health Sciences, Fernando Pessoa University, 4200-150 Porto, Portugal
- Research Department, Portuguese League Against Cancer (NRNorte), 4200-172 Porto, Portugal
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Hassanain O, Alaa M, Khalifa MK, Kamal N, Albagoury A, El Ghoneimy AM. Genetic variants associated with osteosarcoma risk: a systematic review and meta-analysis. Sci Rep 2024; 14:3828. [PMID: 38360742 PMCID: PMC10869693 DOI: 10.1038/s41598-024-53802-w] [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: 12/15/2022] [Accepted: 02/05/2024] [Indexed: 02/17/2024] Open
Abstract
Osteosarcoma (OS) is the most common type of primary bone malignancy. Common genetic variants including single nucleotide polymorphisms (SNPs) have been associated with osteosarcoma risk, however, the results of published studies are inconsistent. The aim of this study was to systematically review genetic association studies to identify SNPs associated with osteosarcoma risk and the effect of race on these associations. We searched the Medline, Embase, Scopus from inception to the end of 2019. Seventy-five articles were eligible for inclusion. These studies investigated the association of 190 SNPs across 79 genes with osteosarcoma, 18 SNPs were associated with the risk of osteosarcoma in the main analysis or in subgroup analysis. Subgroup analysis displayed conflicting effects between Asians and Caucasians. Our review comprehensively summarized the results of published studies investigating the association of genetic variants with osteosarcoma susceptibility, however, their potential value should be confirmed in larger cohorts in different ethnicities.
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Affiliation(s)
- Omneya Hassanain
- Epidemiology and Biostatistics Unit, Clinical Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), 1 Seket el Emam, el Sayeda Zeinab, Cairo, 11441, Egypt.
| | - Mahmoud Alaa
- Basic Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt
| | - Mohamed K Khalifa
- Molecular Pathology Laboratory, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt
| | - Nehal Kamal
- Basic Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt
| | - Aseel Albagoury
- Basic Research, Children's Cancer Hospital Egypt-57357 (CCHE-57357), Cairo, Egypt
| | - Ahmed M El Ghoneimy
- Department of Orthopedic Oncology, Children's Cancer Hospital-57357 (CCHE-57357), Cairo, Egypt
- Department of Orthopedics, Faculty of Medicine, Cairo University, Cairo, Egypt
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Abate M, Walch H, Arora K, Vanderbilt CM, Fei T, Drebin H, Shimada S, Maio A, Kemel Y, Stadler ZK, Schmeltz J, Sihag S, Ku GY, Gu P, Tang L, Vardhana S, Berger MF, Brennan MF, Schultz ND, Strong VE. Unique Genomic Alterations and Microbial Profiles Identified in Patients With Gastric Cancer of African, European, and Asian Ancestry: A Novel Path for Precision Oncology. Ann Surg 2023; 278:506-518. [PMID: 37436885 PMCID: PMC10527605 DOI: 10.1097/sla.0000000000005970] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 07/14/2023]
Abstract
OBJECTIVE Here, we characterize differences in the genetic and microbial profiles of GC in patients of African (AFR), European, and Asian ancestry. BACKGROUND Gastric cancer (GC) is a heterogeneous disease with clinicopathologic variations due to a complex interplay of environmental and biological factors, which may affect disparities in oncologic outcomes.. METHODS We identified 1042 patients with GC with next-generation sequencing data from an institutional Integrated Mutation Profiling of Actionable Cancer Targets assay and the Cancer Genomic Atlas group. Genetic ancestry was inferred from markers captured by the Integrated Mutation Profiling of Actionable Cancer Targets and the Cancer Genomic Atlas whole exome sequencing panels. Tumor microbial profiles were inferred from sequencing data using a validated microbiome bioinformatics pipeline. Genomic alterations and microbial profiles were compared among patients with GC of different ancestries. RESULTS We assessed 8023 genomic alterations. The most frequently altered genes were TP53 , ARID1A , KRAS , ERBB2 , and CDH1 . Patients of AFR ancestry had a significantly higher rate of CCNE1 alterations and a lower rate of KRAS alterations ( P < 0.05), and patients of East Asian ancestry had a significantly lower rate of PI3K pathway alterations ( P < 0.05) compared with other ancestries. Microbial diversity and enrichment did not differ significantly across ancestry groups ( P > 0.05). CONCLUSIONS Distinct patterns of genomic alterations and variations in microbial profiles were identified in patients with GC of AFR, European, and Asian ancestry. Our findings of variation in the prevalence of clinically actionable tumor alterations among ancestry groups suggest that precision medicine can mitigate oncologic disparities.
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Affiliation(s)
- Miseker Abate
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Human Oncology and Pathogenesis Program, MSK
- Department of Surgery, Weill Cornell Medicine
| | - Henry Walch
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK
| | - Kanika Arora
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK
| | | | - Teng Fei
- Department of Epidemiology and Biostatistics, MSK
| | - Harrison Drebin
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Human Oncology and Pathogenesis Program, MSK
| | - Shoji Shimada
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Human Oncology and Pathogenesis Program, MSK
| | - Anna Maio
- Niehaus Center of Inherited Cancer Genomics, MSK
| | - Yelena Kemel
- Niehaus Center of Inherited Cancer Genomics, MSK
| | - Zsofia K. Stadler
- Niehaus Center of Inherited Cancer Genomics, MSK
- Department of Medicine, MSK
- Department of Medicine, Weill Cornell Medicine
| | | | - Smita Sihag
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Department of Surgery, Weill Cornell Medicine
| | - Geoffrey Y. Ku
- Department of Medicine, MSK
- Department of Medicine, Weill Cornell Medicine
| | | | - Laura Tang
- Department of Pathology and Laboratory Medicine, MSK
- Department of Pathology and Laboratory Medicine, WCM
| | - Santosha Vardhana
- Human Oncology and Pathogenesis Program, MSK
- Department of Medicine, MSK
- Department of Medicine, Weill Cornell Medicine
| | - Michael F. Berger
- Marie-Josée and Henry R. Kravis Center for Molecular Oncology, MSK
- Department of Pathology and Laboratory Medicine, MSK
- Department of Pathology and Laboratory Medicine, WCM
| | - Murray F. Brennan
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Department of Surgery, Weill Cornell Medicine
| | | | - Vivian E. Strong
- Department of Surgery, Memorial Sloan Kettering Cancer Center (MSK), New York, NY
- Department of Surgery, Weill Cornell Medicine
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Niu PH, Zhao LL, Wang WQ, Zhang XJ, Li ZF, Luan XY, Chen YT. Survival benefit of younger gastric cancer patients in China and the United States: A comparative study. World J Gastroenterol 2023; 29:1090-1108. [PMID: 36844138 PMCID: PMC9950867 DOI: 10.3748/wjg.v29.i6.1090] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 12/11/2022] [Accepted: 01/05/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND The impact of racial and regional disparity on younger patients with gastric cancer (GC) remains unclear.
AIM To investigate the clinicopathological characteristics, prognostic nomogram, and biological analysis of younger GC patients in China and the United States.
METHODS From 2000 to 2018, GC patients aged less than 40 years were enrolled from the China National Cancer Center and the Surveillance Epidemiology and End Results database. Biological analysis was performed based on the Gene Expression Omnibus database. Survival analysis was conducted via Kaplan-Meier estimates and Cox proportional hazards models.
RESULTS A total of 6098 younger GC patients were selected from 2000 to 2018, of which 1159 were enrolled in the China National Cancer Center, and 4939 were collected from the Surveillance Epidemiology and End Results database. Compared with the United States group, younger patients in China revealed better survival outcomes (P < 0.01). For race/ethnicity, younger Chinese cases also enjoyed a better prognosis than that in White and Black datasets (P < 0.01). After stratification by pathological Tumor-Node-Metastasis (pTNM) stage, a survival advantage was observed in China with pathological stage I, III, and IV (all P < 0.01), whereas younger GC patients with stage II showed no difference (P = 0.16). In multivariate analysis, predictors in China involved period of diagnosis, linitis plastica, and pTNM stage, while race, diagnostic period, sex, location, differentiation, linitis plastica, signet ring cell, pTNM stage, surgery, and chemotherapy were confirmed in the United States group. Prognostic nomograms for younger patients were established, with the area under the curve of 0.786 in the China group and of 0.842 in the United States group. Moreover, three gene expression profiles (GSE27342, GSE51105, and GSE38749) were enrolled in further biological analysis, and distinctive molecular characteristics were identified in younger GC patients among different regions.
CONCLUSION Except for younger cases with pTNM stage II, a survival advantage was observed in the China group with pathological stage I, III, and IV compared to the United States group, which might be partly due to differences in surgical approaches and the improvement of the cancer screening in China. The nomogram model provided an insightful and applicable tool to evaluate the prognosis of younger patients in China and the United States. Furthermore, biological analysis of younger patients was performed among different regions, which might partly explain the histopathological behavior and survival disparity in the subpopulations.
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Affiliation(s)
- Peng-Hui Niu
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Lu-Lu Zhao
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Wan-Qing Wang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao-Jie Zhang
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ze-Feng Li
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Xiao-Yi Luan
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
| | - Ying-Tai Chen
- Department of Pancreatic and Gastric Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China
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Wei H, Zhan XY, Liao X, Li W, Chen H, Deng C, Jin X, Huang Z, Yang M, Zhang C, He Y. Gastric cancer clinical characteristics and their altered trends in South China: An epidemiological study with 2,800 cases spanning 26 years. Front Oncol 2023; 13:976854. [PMID: 36824130 PMCID: PMC9942704 DOI: 10.3389/fonc.2023.976854] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Accepted: 01/02/2023] [Indexed: 02/09/2023] Open
Abstract
BACKGROUND Gastric cancer (GC) is a serious threat to human health. The clinical GC characteristics in China may be impacted by changes in people's lifestyles and the promotion of early GC (EGC) screening. The present study aims to evaluate the recent trends of GC characteristics in South China and search for hazardous factors limiting the survival time of GC patients. METHODS Data on GC patients that were hospitalized in the Department of Digestive Center, the First Affiliated Hospital, Sun Yat-sen University, from 1994 to 2019 were collected and divided into two categories according to the time when the EGC screening began in China: the PRE group (previous 13 years, 1994-2006) and the PAS group (past 13 years, 2007-2019). RESULTS We found that, although the 5-year survival rate increased in the PAS group compared with the PRE group (P < 0.0001), patients with age ≥60 years or Borrmann type IV still had a worse prognosis. In the PAS group, the larger percentages of elderly patients and patients with Borrmann type IV in the lymphatic metastases (N1) group (41.0% vs. 51.1%, P = 0.0014) and stage IV subgroup (20.7% vs. 32.2%, P = 0.016), respectively, when compared with the PRE group, may have contributed to the poor outcome of GC. By comparing the odds ratio (OR) of 5-year overall survival (OS) in the two 13-year periods, female sex and T2 turned into risk factors because of a greater proportion of Borrmann type IV or elderly patients in the PAS group (OR = 0.983, 95% CI = 0.723-1.336 vs. OR = 1.277, 95% CI = 1.028-1.586 and OR = 1.545, 95% CI = 0.499-4.775 vs. OR = 2.227, 95% CI = 1.124-4.271, respectively). CONCLUSIONS Despite the GC epidemiology changes, the overall prognosis of GC patients has improved in South China. However, old age and Borrmann type IV are still the major restrictions affecting the survival of GC patients, a situation which calls for additional attention.
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Affiliation(s)
- Hongfa Wei
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Xiao-Yong Zhan
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Xianying Liao
- Invasive Technology Department of the Cancer Hospital of Shantou University Medical College, Shantou, China
| | - Wenchao Li
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Hui Chen
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
| | - Cuncan Deng
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Xinghan Jin
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Zhangsen Huang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
| | - Mo Yang
- Scientific Research Center, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, China
- *Correspondence: Yulong He, ; Changhua Zhang, ; Mo Yang,
| | - Changhua Zhang
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- *Correspondence: Yulong He, ; Changhua Zhang, ; Mo Yang,
| | - Yulong He
- Digestive Diseases Center, The Seventh Affiliated Hospital of Sun Yat-sen University, Shenzhen, China
- *Correspondence: Yulong He, ; Changhua Zhang, ; Mo Yang,
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Zhang Z, Liu Z, Chen Z. Comparison of Treatment Efficacy and Survival Outcomes Between Asian and Western Patients With Unresectable Gastric or Gastro-Esophageal Adenocarcinoma: A Systematic Review and Meta-Analysis. Front Oncol 2022; 12:831207. [PMID: 35321436 PMCID: PMC8936077 DOI: 10.3389/fonc.2022.831207] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2021] [Accepted: 02/15/2022] [Indexed: 12/02/2022] Open
Abstract
Background Gastric cancer and gastro-esophageal adenocarcinoma are geographically heterogeneous diseases. Previous studies suggested that Asian and Western patients with late-stage gastric or gastro-esophageal adenocarcinoma possess distinct survival outcomes. However, the interregional differences of multiple systemic therapies in unresectable diseases have not been comprehensively described. Materials and Methods We searched PubMed-MEDLINE, Embase, Web of Science and Cochrane Library from inception to 31 October 2021 and reviewed major conference abstracts for controlled trials of systemic therapies in unresectable gastric or gastro-esophageal adenocarcinoma that reported hazard ratios stratified by geographical region. The primary measurements were overall survival and progression-free survival. The pooled hazard ratios and 95% confidence intervals for overall survival and progression-free survival in Asian and Western populations were calculated using a random effect model. A linear regression model was adopted to compare the overall survival and progression-free survival between Asian and Western patients. Results A total of 9033 patients from 20 studies were included for analysis. Immunotherapy was associated with an improvement in the overall survival for both Asian (hazard ratio, 0.80; 95% confidence interval, 0.65–0.98) and Western (hazard ratio, 0.90; 95% confidence interval, 0.81–1.00) patients, with no significant difference between the two groups (P = 0.32). Trends of survival benefit with anti-HER2 therapy and anti-angiogenic therapy versus control were observed in both Asian and Western patients, although statistical significance was not denoted. Subgroup analyses yielded a statistically superior overall survival of Asian versus Western patients in trials that investigated first-line immunotherapy (P = 0.04). Due to the linear regression analyses with scatter plot graphs, Asian patients showed a higher overall survival, but not progression-free survival, than Western patients irrespective of treatment type. Conclusion Asian and Western patients with unresectable gastric or gastro-esophageal adenocarcinoma show similar responses to systemic therapies with limited interregional differences. Exceptionally, first-line immunotherapy could elicit superior survival among Asian populations. In addition, Asian patients with gastric or gastro-esophageal adenocarcinoma display a superior OS compared with Western counterparts.
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Affiliation(s)
- Zhening Zhang
- Department of General Surgery, Peking University First Hospital, Beijing, China
- Department of Gastrointestinal Oncology, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zining Liu
- Department of General Surgery, Peking University First Hospital, Beijing, China
- Department of Gastrointestinal Cancer Center, Key Laboratory of Carcinogenesis and Translational Research, Peking University Cancer Hospital and Institute, Beijing, China
| | - Zeyang Chen
- Department of General Surgery, Peking University First Hospital, Beijing, China
- *Correspondence: Zeyang Chen,
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Nieuwenburg SAV, Mommersteeg MC, Eikenboom EL, Yu B, den Hollander WJ, Holster IL, den Hoed CM, Capelle LG, Tang TJ, Anten MP, Prytz-Berset I, Witteman EM, ter Borg F, Burger JPW, Bruno MJ, Fuhler GM, Peppelenbosch MP, Doukas M, Kuipers EJ, Spaander MC. Factors associated with the progression of gastric intestinal metaplasia: a multicenter, prospective cohort study. Endosc Int Open 2021; 9:E297-E305. [PMID: 33655025 PMCID: PMC7892268 DOI: 10.1055/a-1314-6626] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Indexed: 12/13/2022] Open
Abstract
Background and study aims Gastric cancer (GC) is usually preceded by premalignant gastric lesions (GPLs) such as gastric intestinal metaplasia (GIM). Information on risk factors associated with neoplastic progression of GIM are scarce. This study aimed to identify predictors for progression of GIM in areas with low GC incidence. Patients and methods The Progression and Regression of Precancerous Gastric Lesions (PROREGAL) study includes patients with GPL. Patients underwent at least two upper endoscopies with random biopsy sampling. Progression of GIM means an increase in severity according to OLGIM (operative link on gastric intestinal metaplasia) during follow-up (FU). Family history and lifestyle factors were determined through questionnaires. Serum Helicobacter pylori infection, pepsinogens (PG), gastrin-17 and GC-associated single nucleotide polymorphisms (SNPs) were determined. Cox regression was performed for risk analysis and a chi-squared test for analysis of single nucleotide polymorphisms. Results Three hundred and eight patients (median age at inclusion 61 years, interquartile range (IQR: 17; male 48.4 %; median FU 48 months, IQR: 24) were included. During FU, 116 patients (37.7 %) showed progression of IM and six patients (1.9 %) developed high-grade dysplasia or GC. The minor allele (C) on TLR4 (rs11536889) was inversely associated with progression of GIM (OR 0.6; 95 %CI 0.4-1.0). Family history (HR 1.5; 95 %CI 0.9-2.4) and smoking (HR 1.6; 95 %CI 0.9-2.7) showed trends towards progression of GIM. Alcohol use, body mass index, history of H. pylori infection, and serological markers were not associated with progression. Conclusions Family history and smoking appear to be related to an increased risk of GIM progression in low GC incidence countries. TLR4 (rs11536889) showed a significant inverse association, suggesting that genetic information may play a role in GIM progression.
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Affiliation(s)
- S. A. V. Nieuwenburg
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - M. C. Mommersteeg
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - E. L. Eikenboom
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - B. Yu
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | | | - I. Lisanne Holster
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Caroline M. den Hoed
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - L. G Capelle
- Meander Medical Centre, Amersfoort, the Netherlands
| | - Thjon J. Tang
- IJsselland Hospital, Capelle aan den IJssel, The Netherlands
| | | | | | | | - F. ter Borg
- Deventer Hospital, Deventer, The Netherlands
| | - Jordy P. W. Burger
- Department of Gastroenterology and Hepatology, Rijnstate, Arnhem, The Netherlands
| | - Marco J. Bruno
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - G. M. Fuhler
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Maikel P. Peppelenbosch
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Michael Doukas
- Department of Pathology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Ernst J. Kuipers
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
| | - Manon C.W. Spaander
- Departments of Gastroenterology and Hepatology, Erasmus University Medical Centre, Rotterdam, The Netherlands
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9
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Possible Roles of Interleukin-4 and -13 and Their Receptors in Gastric and Colon Cancer. Int J Mol Sci 2021; 22:ijms22020727. [PMID: 33450900 PMCID: PMC7828336 DOI: 10.3390/ijms22020727] [Citation(s) in RCA: 42] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 01/04/2021] [Accepted: 01/08/2021] [Indexed: 02/08/2023] Open
Abstract
Interleukin (IL)-4 and -13 are structurally and functionally related cytokines sharing common receptor subunits. They regulate immune responses and, moreover, are involved in the pathogenesis of a variety of human neoplasms. Three different receptors have been described for IL-4, but only IL-4 receptor type II (IL-4Rα/IL-13Rα1) is expressed in solid tumors. While IL-13 can also bind to three different receptors, IL-13 receptor type I (IL-4Rα/IL-13Rα1/IL-13Rα2) and type II (IL-4Rα/IL-13Rα1) are expressed in solid tumors. After receptor binding, IL-4 and IL-13 can mediate tumor cell proliferation, survival, and metastasis in gastric or colon cancer. This review summarizes the results about the role of IL-4/IL-13 and their receptors in gastric and colon cancer.
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10
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Panarese A, Galatola G, Armentano R, Pimentel-Nunes P, Ierardi E, Caruso ML, Pesce F, Lenti MV, Palmitessa V, Coletta S, Shahini E. Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions. World J Gastroenterol 2020; 26:3834-3850. [PMID: 32774061 PMCID: PMC7383846 DOI: 10.3748/wjg.v26.i26.3834] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2020] [Revised: 06/20/2020] [Accepted: 06/30/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection has been associated with a long-term risk of precancerous gastric conditions (PGC) even after H. pylori eradication. AIM To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC, before/after H. pylori eradication. METHODS We studied 85 consecutive patients with H. pylori-related gastritis with/without PGC before and 6 mo after proven H. pylori eradication. Kimura-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications, were applied to assess the endoscopic extension of atrophy and intestinal metaplasia. The histological result was considered to be the gold standard. The Sydney System, the Operative-Link on Gastritis-Assessment, and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis, atrophy and intestinal metaplasia, whereas dysplasia was graded according to World Health Organization classification. Serum anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was suspected. RESULTS After H. pylori eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia, disappeared or decreased in 100% and 96.5% of patients respectively, whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not change. Low-Grade Dysplasia prevalence was similar on random biopsies before and after H. pylori eradication (17.6% vs 10.6%, P = 0.19), but increased in patients with visible lesions (0% vs 22.4%, P < 0.0001). At a multivariate analysis, the probability for detecting dysplasia after resolution of H. pylori-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia, greater alcohol consumption, and anti-parietal cell antibody and/or anti-intrinsic factor positivity [odds ratio (OR) = 3.88, 95% confidence interval (CI): 1.31-11.49, P = 0.01; OR = 3.10, 95%CI: 1.05-9.12, P = 0.04 and OR = 5.47, 95%CI: 1.33-22.39, P < 0.04, respectively]. CONCLUSION High-Resolution White-Light Endoscopy with Narrow-Band Imaging allows an accurate diagnosis of Low-Grade Dysplasia on visible lesions after regression of H. pylori-induced chronic gastritis. Patients with an overlap between autoimmune/H. pylori-induced gastritis may require more extensive gastric mapping.
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Affiliation(s)
- Alba Panarese
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Raffaele Armentano
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Pedro Pimentel-Nunes
- Center for Research in Health Technologies and Information Systems, Faculty of Medicine, Porto 4200072, Portugal
- Surgery and Physiology Department, Faculty of Medicine of the University of Porto, Porto 4200072, Portugal
| | - Enzo Ierardi
- Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Lucia Caruso
- Sergio Coletta Department of Clinical Pathology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | - Francesco Pesce
- Nephrology Section, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Marco Vincenzo Lenti
- First Department of Internal Medicine, San Matteo Hospital Foundation, University of Pavia, Pavia 27100, Italy
| | - Valeria Palmitessa
- Laboratory of Microbiology and Virology, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
| | | | - Endrit Shahini
- Department of Gastroenterology and Digestive Endoscopy, National Institute of Gastroenterology "S De Bellis", Research Hospital, Castellana Grotte 70013, Italy
- Giovanni Galatola Gastroenterology Unit, Institute for Cancer Research and Treatment, Turin 10121, Italy
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11
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Yao K, Uedo N, Kamada T, Hirasawa T, Nagahama T, Yoshinaga S, Oka M, Inoue K, Mabe K, Yao T, Yoshida M, Miyashiro I, Fujimoto K, Tajiri H. Guidelines for endoscopic diagnosis of early gastric cancer. Dig Endosc 2020; 32:663-698. [PMID: 32275342 DOI: 10.1111/den.13684] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2020] [Accepted: 04/01/2020] [Indexed: 02/06/2023]
Abstract
The Japan Gastroenterological Endoscopy Society developed the Guideline for Endoscopic Diagnosis of Early Gastric Cancer based on scientific methods. Endoscopy for the diagnosis of early gastric cancer has been acknowledged as a useful and highly precise examination, and its use has become increasingly more common in recent years. However, the level of evidence in this field is low, and it is often necessary to determine recommendations based on expert consensus only. This clinical practice guideline consists of the following sections to provide the current guideline: [I] Risk stratification of gastric cancer before endoscopic examination, [II] Detection of early gastric cancer, [III] Qualitative diagnosis of early gastric cancer, [IV] Diagnosis to choose the therapeutic strategy for gastric cancer, [V] Risk stratification after endoscopic examination, and [VI] Surveillance of early gastric cancer.
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Affiliation(s)
- Kenshi Yao
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Noriya Uedo
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Tomoari Kamada
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | | | | | | | - Masashi Oka
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Kazuhiko Inoue
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Katsuhiro Mabe
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | - Takashi Yao
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | | | - Isao Miyashiro
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
| | | | - Hisao Tajiri
- Japan Gastroenterological Endoscopy Society, Tokyo, Japan
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12
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Hirbod-Mobarakeh A, Shabani M, Keshavarz-Fathi M, Delavari F, Amirzargar AA, Nikbin B, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2020:417-478. [DOI: 10.1007/978-3-030-30845-2_20] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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13
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Li H, Wang C, Wei Z, Chen W, Guo Z, He Y, Zhang C. Differences in the prognosis of gastric cancer patients of different sexes and races and the molecular mechanisms involved. Int J Oncol 2019; 55:1049-1068. [PMID: 31793655 PMCID: PMC6776187 DOI: 10.3892/ijo.2019.4885] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Accepted: 09/04/2019] [Indexed: 12/11/2022] Open
Abstract
To evaluate the prognostic and molecular mechanisms of sex and racial differences in gastric cancer, data from two large centers were used to retrospectively analyze the survival of gastric cancer patients with regard to sex and racial differences. In examining the molecular mechanism of sex in gastric cancer patients of different races, data from The Cancer Genome Atlas database were used to analyze differentially expressed genes (DEGs), and Gene Ontology (GO) enrichment and DNA methylation analyses were performed. Among White gastric cancer patients, it was found that the survival prognosis for females was better than that for males; conversely, among Chinese patients, males had a better prognosis. For African Americans, sex may have an impact on gastric cancer, but this relationship was unclear. The core DEGs between the different sexes included glycogenin 2 pseudogene 1, ribosomal protein S4 Y-linked 1, taxilin-γ and eukaryotic translation initiation factor 1A X-linked among White patients, and GO enrichment analysis revealed that these genes act mainly through RNA binding and transcription pathways. Among Black patients, core DEGs included DnaJ heat shock protein family (Hsp40) member C5, histone deacetylase 10, neogenin 1 and SMG5 nonsense mediated mRNA decay factor, which are mainly related to pathways of cellular structural changes based on GO enrichment analysis. For Asian patients, core DEGs included zinc finger protein Y-linked, thymosin β4 Y-linked, zinc finger protein 787 and ubiquitously transcribed tetratricopeptide repeat containing, Y-linked, participating in cell surface receptor-associated signal transduction and G-protein coupled receptor protein signaling pathways, according to GO. The expression of different core genes and differences in path ways are likely to be the main causes affecting the variation observed among gastric cancer patients of different races and sexes.
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Affiliation(s)
- Huafu Li
- Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
| | - Chunming Wang
- Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
| | - Zhewei Wei
- Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
| | - Wei Chen
- Department of Gastrointestinopancreatic Surgery, The First Affiliated Hospital of Sun Yat‑Sen University, Guangzhou, Guangdong 510080, P.R. China
| | - Zicong Guo
- Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
| | - Yulong He
- Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
| | - Changhua Zhang
- Digestive Medicine Center, The Seventh Affiliated Hospital of Sun Yat‑Sen University, Shenzhen, Guangdong 518107, P.R. China
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Torruella-Loran I, Ramirez Viña MK, Zapata-Contreras D, Muñoz X, Garcia-Ramallo E, Bonet C, Gonzalez CA, Sala N, Espinosa-Parrilla Y. rs12416605:C>T in MIR938 associates with gastric cancer through affecting the regulation of the CXCL12 chemokine gene. Mol Genet Genomic Med 2019; 7:e832. [PMID: 31273931 PMCID: PMC6687864 DOI: 10.1002/mgg3.832] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2019] [Revised: 05/23/2019] [Accepted: 05/31/2019] [Indexed: 12/11/2022] Open
Abstract
Background MicroRNAs are small regulatory RNAs with important roles in carcinogenesis. Genetic variants in these regulatory molecules may contribute to disease. We aim to identify allelic variants in microRNAs as susceptibility factors to gastric cancer using association studies and functional approaches. Methods Twenty‐one single nucleotide variants potentially functional, because of their location in either the seed, mature or precursor region of 22 microRNAs, were selected for association studies. Genetic association with gastric cancer in 365 cases and 1,284 matched controls (European Prospective Investigation into Cancer and Nutrition Cohort) was analysed using logistic regression. MicroRNA overexpression, transcriptome analysis, and target gene validation experiments were performed for functional studies. Results rs3746444:T>C, in the seed of MIR499A and mature MIR499B, associated with the cardia adenocarcinoma location; rs12416605:C>T, in the seed of MIR938, associated with the diffuse subtype; and rs2114358:T>C, in the precursor MIR1206, associated with the noncardia phenotype. In all cases, the association was inverse, indicating a protective affect against gastric cancer of the three minor allelic variants. MIR499 rs3746444:T>C and MIR1206 rs2114358:T>C are reported to affect the expression of these miRNAs, but the effect of MIR938 rs12416605:C>T is unknown yet. Functional approaches showed that the expression of MIR938 is affected by rs12416605:C>T and revealed that MIR938 could regulate a subset of cancer‐related genes in an allele‐specific fashion. Furthermore, we demonstrated that CXCL12, a chemokine participating in gastric cancer metastasis, is specifically regulated by only one of the rs12416605:C>T alleles. Conclusion rs12416605 appears to be involved in gastric cancer by affecting the regulatory function of MIR938 on genes related to this cancer type, particularly on CXCL12 posttranscriptional regulation.
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Affiliation(s)
- Ignasi Torruella-Loran
- Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra-CSIC), Barcelona, Spain
| | - María Karla Ramirez Viña
- School of Medicine, Universidad de Magallanes, Punta Arenas, Chile.,Laboratory of Molecular Medicine LMM, Center for Education, Healthcare and Investigation CADI, Universidad de Magallanes, Punta Arenas, Chile
| | - Daniela Zapata-Contreras
- School of Medicine, Universidad de Magallanes, Punta Arenas, Chile.,Laboratory of Molecular Medicine LMM, Center for Education, Healthcare and Investigation CADI, Universidad de Magallanes, Punta Arenas, Chile
| | - Xavier Muñoz
- Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.,Hereditary Cancer Program, Catalan Institute of Oncology, IDIBELL, Hospitalet de Llobregat, Barcelona, Spain
| | - Eva Garcia-Ramallo
- Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra-CSIC), Barcelona, Spain
| | - Catalina Bonet
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-Bellvitge Biomedical Research Institute (ICO-IDIBELL), Barcelona, Spain
| | - Carlos A Gonzalez
- Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-Bellvitge Biomedical Research Institute (ICO-IDIBELL), Barcelona, Spain
| | - Núria Sala
- Molecular Epidemiology Group, Translational Research Laboratory, Catalan Institute of Oncology-IDIBELL, Barcelona, Spain.,Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-Bellvitge Biomedical Research Institute (ICO-IDIBELL), Barcelona, Spain
| | - Yolanda Espinosa-Parrilla
- Department of Experimental and Health Sciences, IBE, Institute of Evolutionary Biology (Universitat Pompeu Fabra-CSIC), Barcelona, Spain.,School of Medicine, Universidad de Magallanes, Punta Arenas, Chile.,Laboratory of Molecular Medicine LMM, Center for Education, Healthcare and Investigation CADI, Universidad de Magallanes, Punta Arenas, Chile
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15
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Raad M, Bayat A, Sharafshah A, Amiri AZ, Zohour MM, Ahmadvand M. Association and in silico investigations of miR-302c insertion/deletion variant as a novel biomarker with susceptibility to gastric cancer. J Cell Biochem 2019; 120:18946-18955. [PMID: 31219213 DOI: 10.1002/jcb.29215] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2019] [Accepted: 06/04/2019] [Indexed: 11/07/2022]
Abstract
Gastric cancer (GC) is the fifth most prevalent malignant tumor and the third most frequent cause of cancer mortality worldwide. rs199971565 is an insertion/deletion (INDEL) located in microRNA-302c (miR-302c) seed site, which may affect its function and biogenesis. There is no genetic association study investigating this INDEL with any disease till now. Thus, the current study was conducted to investigate the association of rs199971565 with susceptibility to GC in an Iranian population. In addition, in silico studies were performed to reveal the possible functional significance of this INDEL. A total of 378 subjects were genotyped through amplification refractory mutation system PCR (ARMS-PCR) after DNA extraction from peripheral blood by the salting out procedure. Also, in silico analyses were performed through databases and web tools including MiRNASNP V2.0, miRWalk V2.0, miRTarBase, DAVID V6.8, RNAfold, PHDcleave, miRmap, and STarMir. Results revealed that there was an association between rs199971565 and the incidence risk of GC under a recessive (P = .04, odds ratio [OR] = 18.73; 95% confidence interval [CI] = 1.07-326.95) model of inheritance. Also, compared to the Ins allele, the Del allele significantly increased the risk of GC (P = .01, OR = 2.02; 95% CI = 1.11-3.66). Further analyses showed no significant association in age and sex between two study groups (P = .216 and P = .798, respectively). In conclusion, for the first time, this study indicated the association and in silico investigations of rs199971565 and suggested it as a novel INDEL biomarker located in the seed site of miR-302c, which may have crucial roles in the susceptibility to GC and its incidence risk.
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Affiliation(s)
- Mohammad Raad
- Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran
| | - Amir Bayat
- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Alireza Sharafshah
- Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Ali Zahedi Amiri
- Manitoba Centre for Proteomics and Systems Biology, John Buhler Research Centre, Winnipeg, Canada
| | - Mostafa Montazer Zohour
- Genetics of Non-Communicable Disease Research Center, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Mohammad Ahmadvand
- Hematology-Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
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Takeshima H, Ushijima T. Accumulation of genetic and epigenetic alterations in normal cells and cancer risk. NPJ Precis Oncol 2019; 3:7. [PMID: 30854468 PMCID: PMC6403339 DOI: 10.1038/s41698-019-0079-0] [Citation(s) in RCA: 161] [Impact Index Per Article: 26.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2018] [Accepted: 02/11/2019] [Indexed: 12/17/2022] Open
Abstract
Cancers develop due to the accumulation of genetic and epigenetic alterations. Genetic alterations are induced by aging, mutagenic chemicals, ultraviolet light, and other factors; whereas, epigenetic alterations are mainly by aging and chronic inflammation. The accumulation and patterns of alterations in normal cells reflect our past exposure levels and life history. Most accumulated alterations are considered as passengers, but their accumulation is correlated with cancer drivers. This has been shown for aberrant DNA methylation but has only been speculated for genetic alterations. However, recent technological advancements have enabled measurement of rare point mutations, and studies have shown that their accumulation levels are indeed correlated with cancer risk. When the accumulation levels of aberrant DNA methylation and point mutations are combined, risk prediction becomes even more accurate. When high levels of alterations accumulate, the tissue has a high risk of developing cancer or even multiple cancers and is considered as a “cancerization field”, with or without expansion of physiological patches of clonal cells. In this review, we describe the formation of a cancerization field and how we can apply its detection in precision cancer risk diagnosis.
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Affiliation(s)
- Hideyuki Takeshima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan
| | - Toshikazu Ushijima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, 104-0045 Tokyo, Japan
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17
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Ghatak S, Chakraborty P, Sarathbabu S, Pautu JL, Zohmingthanga J, Lalchhandama C, Kumar NS. Influence of TP53 gene somatic mutations in Helicobacter pylori infected gastric tumor. Meta Gene 2018. [DOI: 10.1016/j.mgene.2018.05.008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/29/2022] Open
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18
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Sultana Z, Bankura B, Pattanayak AK, Sengupta D, Sengupta M, Saha ML, Panda CK, Das M. Association of Interleukin-1 beta and tumor necrosis factor-alpha genetic polymorphisms with gastric cancer in India. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 2018; 59:653-667. [PMID: 30094865 DOI: 10.1002/em.22208] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 03/18/2018] [Accepted: 05/03/2018] [Indexed: 06/08/2023]
Abstract
Interleukin 1 beta (IL-1β) and Tumor necrosis factor alpha (TNF-α) are key inflammatory cytokines whose polymorphisms have been correlated with increased susceptibility to gastric cancer (GC). Since geographical and racial differences exist in cancer rates, our study was aimed to evaluate the first possible association of polymorphisms in these genes with GC risk in West Bengal, India. Polymorphisms in IL-1β and TNF-α genes were genotyped in 120 GC patients and 135 healthy individuals. Combined effect of the SNPs in both genes with GC risk was determined through allele dosage analysis (ADA) and the survival data were analyzed by Log Rank Test. The study results revealed that IL-1β rs1143627: T > C, rs16944: C > T (p = 0.001;OR = 1.85; 95% CI 1.30-2.63) and rs1143633: G > A (p < 0.0001; OR = 2.53; 95% CI 1.67-3.83) and TNF-α rs1800630: C > A, rs1799964: T > C (p < 0.0001; OR = 2.31; 95% CI 1.54-3.46) polymorphisms significantly contributed toward GC risk. Moreover, ADA showed that carriage of 7 "effective" risk alleles conferred a risk of almost 10-fold in comparison to individuals carrying less than 3 "effective" risk alleles. Our survival analysis also indicated a significant association between IL-1β rs1143627: T > C and rs16944: C > T and patient survivability. The presence of H. pylori enhanced the risk in individuals with IL-1β rs1143627:CC and rs16944:TT genotypes. Further, meta-analysis revealed significant association of IL-1β rs1143627: T > C (p = 0.026; OR = 4.165; 95% CI 1.18-14.65) and rs16944: C > T (p = 0.01; OR = 5.49; 95% CI 1.48-20.37) in presence of H. pylori with gastric cancer in Asian population though no significant difference (p > 0.05) was found when compared to absence of H. pylori Environ. Mol. Mutagen. 59:653-667, 2018. © 2018 Wiley Periodicals, Inc.
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Affiliation(s)
- Zareen Sultana
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | - Biswabandhu Bankura
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
| | | | - Debmalya Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Mainak Sengupta
- Department of Genetics, University of Calcutta, West Bengal, 700019, India, Kolkata
| | - Makhan Lal Saha
- Department of Surgery, Institute of Post Graduate Medical Education &Research, Kolkata, West Bengal, 700020, India
| | - Chinmay Kumar Panda
- Department of Oncogene Regulation and Viral Associated Human Cancer, Chittaranjan Cancer Research Institute, Kolkata, West Bengal, 700026, India
| | - Madhusudan Das
- Department of Zoology, University of Calcutta, Kolkata, West Bengal, 700019, India
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Fernández-Coto DL, Gil J, Hernández A, Herrera-Goepfert R, Castro-Romero I, Hernández-Márquez E, Arenas-Linares AS, Calderon-Sosa VT, Sanchez-Aleman MÁ, Mendez-Tenorio A, Encarnación-Guevara S, Ayala G. Quantitative proteomics reveals proteins involved in the progression from non-cancerous lesions to gastric cancer. J Proteomics 2018; 186:15-27. [DOI: 10.1016/j.jprot.2018.07.013] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 06/21/2018] [Accepted: 07/18/2018] [Indexed: 12/18/2022]
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20
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Pucułek M, Machlowska J, Wierzbicki R, Baj J, Maciejewski R, Sitarz R. Helicobacter pylori associated factors in the development of gastric cancer with special reference to the early-onset subtype. Oncotarget 2018; 9:31146-31162. [PMID: 30123433 PMCID: PMC6089554 DOI: 10.18632/oncotarget.25757] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2018] [Accepted: 06/22/2018] [Indexed: 02/07/2023] Open
Abstract
Nowadays, gastric cancer is one of the most common neoplasms and the fourth cause of cancer-related death on the world. Regarding the age at the diagnosis it is divided into early-onset gastric carcinoma (45 years or younger) and conventional gastric cancer (older than 45). Gastric carcinomas are rarely observed in young population and rely mostly on genetic factors, therefore provide the unique model to study genetic and environmental alternations. The latest research on early-onset gastric cancer are trying to explain molecular and genetic basis, because young patients are less exposed to environmental factors predisposing to cancer. In the general population, Helicobacter pylori, has been particularly associated with intestinal subtype of gastric cancers. The significant association of Helicobacter pylori infection in young patients with gastric cancers suggests that the bacterium has an etiologic role in both diffuse and intestinal subtypes of early-onset gastric cancers. In this paper we would like to ascertain the possible role of Helicobacter pylori infection in the development of gastric carcinoma in young patients. The review summarizes recent literature on early-onset gastric cancers with special reference to Helicobacter pylori infection.
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Affiliation(s)
| | | | - Ryszard Wierzbicki
- Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Poland
- Department of Surgical Oncology, Medical University of Lublin, Poland
| | - Jacek Baj
- Department of Human Anatomy, Medical University of Lublin, Poland
| | | | - Robert Sitarz
- Department of Human Anatomy, Medical University of Lublin, Poland
- Department of Surgery with Trauma, Orthopaedic and Urological Subunit, Independent Public Health Care Center of the Ministry of Interior and Administration in Lublin, Poland
- Department of Surgery, St. John's Cancer Center, Lublin, Poland
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21
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Dai W, Li Q, Liu BY, Li YX, Li YY. Differential networking meta-analysis of gastric cancer across Asian and American racial groups. BMC SYSTEMS BIOLOGY 2018; 12:51. [PMID: 29745833 PMCID: PMC5998874 DOI: 10.1186/s12918-018-0564-z] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Background Gastric Carcinoma is one of the most lethal cancer around the world, and is also the most common cancers in Eastern Asia. A lot of differentially expressed genes have been detected as being associated with Gastric Carcinoma (GC) progression, however, little is known about the underlying dysfunctional regulation mechanisms. To address this problem, we previously developed a differential networking approach that is characterized by involving differential coexpression analysis (DCEA), stage-specific gene regulatory network (GRN) modelling and differential regulation networking (DRN) analysis. Result In order to implement differential networking meta-analysis, we developed a novel framework which integrated the following steps. Considering the complexity and diversity of gastric carcinogenesis, we first collected three datasets (GSE54129, GSE24375 and TCGA-STAD) for Chinese, Korean and American, and aimed to investigate the common dysregulation mechanisms of gastric carcinogenesis across racial groups. Then, we constructed conditional GRNs for gastric cancer corresponding to normal and carcinoma, and prioritized differentially regulated genes (DRGs) and gene links (DRLs) from three datasets separately by using our previously developed differential networking method. Based on our integrated differential regulation information from three datasets and prior knowledge (e.g., transcription factor (TF)-target regulatory relationships and known signaling pathways), we eventually generated testable hypotheses on the regulation mechanisms of two genes, XBP1 and GIF, out of 16 common cross-racial DRGs in gastric carcinogenesis. Conclusion The current cross-racial integrative study from the viewpoint of differential regulation networking provided useful clues for understanding the common dysfunctional regulation mechanisms of gastric cancer progression and discovering new universal drug targets or biomarkers for gastric cancer. Electronic supplementary material The online version of this article (10.1186/s12918-018-0564-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Wentao Dai
- Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China.,Shanghai Engineering Research Center of Pharmaceutical Translation & Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China
| | - Quanxue Li
- Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China.,School of biotechnology, East China University of Science and Technology, Shanghai, 200237, China
| | - Bing-Ya Liu
- Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People's Republic of China
| | - Yi-Xue Li
- Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China. .,School of biotechnology, East China University of Science and Technology, Shanghai, 200237, China. .,Shanghai Engineering Research Center of Pharmaceutical Translation & Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China. .,Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
| | - Yuan-Yuan Li
- Shanghai Center for Bioinformation Technology, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China. .,School of biotechnology, East China University of Science and Technology, Shanghai, 200237, China. .,Shanghai Engineering Research Center of Pharmaceutical Translation & Shanghai Industrial Technology Institute, 1278 Keyuan Road, Shanghai, 201203, People's Republic of China. .,Key Lab of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China.
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22
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Association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer risk: a meta-analysis. Oncotarget 2018; 7:66109-66118. [PMID: 27623072 PMCID: PMC5323219 DOI: 10.18632/oncotarget.11848] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2015] [Accepted: 07/14/2016] [Indexed: 12/18/2022] Open
Abstract
Published data on the association between cyclin D1 (CCND1) G870A polymorphism and gastric cancer (GC) risk are inconclusive. Thus, we conducted a meta-analysis to evaluate the relationship between CCND1 G870A polymorphism and GC risk. We searched PubMed, EMBASE, Web of science and the Cochrane Library up to June 12, 2015 for relevant studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations. Nine studies published from 2003 to 2014, with a total of 1813 cases and 2173 controls, were included in this meta-analysis. The pooled results showed that there was no association between CCND1 G870A polymorphism and GC risk in any genetic model. The subgroup analysis stratified by ethnicity showed an increased breast cancer risk in Caucasian based on heterozygote comparison (GA vs. GG: OR=1.49, 95% CI=1.06-2.10, P=0.02). We found the same association in population based (PB) stratified analyses by Source of controls (AA vs. GG: OR=1.39, 95% CI=1.01-1.93, 0.05). When stratifying by the type, Sex and H. pylori infection in dominant model, Interestingly, we found the opposite result in Male (AA + GA vs. GG: OR=0.5, 95% CI=0.33-0.76, P=0.001), there were no association between CCND1 G870A polymorphism and GC risk in any other subgroup. This meta-analysis suggests that CCND1 G870A polymorphism is a risk factor for susceptibility to GC in Caucasians and in general populations. While, CCND1 G870A polymorphism plays a possible protective effect in GC in Male. Further large scale multicenter epidemiological studies are warranted to confirm this finding.
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23
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Ruíz-García E, Guadarrama-Orozco J, Vidal-Millán S, Lino-Silva LS, López-Camarillo C, Astudillo-de la Vega H. Gastric cancer in Latin America. Scand J Gastroenterol 2018; 53:124-129. [PMID: 29275643 DOI: 10.1080/00365521.2017.1417473] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2017] [Revised: 12/07/2017] [Accepted: 12/09/2017] [Indexed: 02/04/2023]
Abstract
Every year, cancer affects more than one million Latin Americans. The increasing incidence of cancer could be secondary to an aging population, westernization of life style, and urbanization. LA has among the highest incidence rates of gastric cancer, compared to other countries. In this review, different studies on gastric cancer and its relation with risks factors, such as infections, diet and life styles typical of LA, besides the different molecular alterations of that specific population (mainly at a genetic polymorphism level) are analyzed. An exhaustive research was made in PubMed, MEDLINE and Embase of the most relevant studies conducted in the last 27 years (1990-2017) in LA.
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Affiliation(s)
- Erika Ruíz-García
- a Laboratorio de Medicina Traslacional , Instituto Nacional de Cancerología , Ciudad de México , México
- b Departamento de Tumores Gastro-Intestinales , Instituto Nacional de Cancerología , Ciudad de México , México
| | - Jorge Guadarrama-Orozco
- a Laboratorio de Medicina Traslacional , Instituto Nacional de Cancerología , Ciudad de México , México
| | - Silvia Vidal-Millán
- c Laboratorio de Diagnóstico Molecular , Instituto Nacional de Cancerología , Ciudad de México , México
| | - Leonardo S Lino-Silva
- d Departamento de Patología , Instituto Nacional de Cancerología , Ciudad de México , México
| | - César López-Camarillo
- e Posgrado en Ciencias Genómicas , Universidad Autónoma de la Ciudad de México , Ciudad de México , México
| | - Horacio Astudillo-de la Vega
- f Laboratorio de Investigación Traslacional en Cáncer y Terapia Celular , Centro Médico Siglo XXI, IMSS , Ciudad de México , México
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24
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Taipale M, Solovieva S, Leino-Arjas P, Männikkö M. Functional polymorphisms in asporin and CILP together with joint loading predispose to hand osteoarthritis. BMC Genet 2017; 18:108. [PMID: 29233086 PMCID: PMC5727665 DOI: 10.1186/s12863-017-0585-4] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2017] [Accepted: 12/07/2017] [Indexed: 01/07/2023] Open
Abstract
Background Osteoarthritis (OA) is the most common degenerative joint disease afflicting people in the Western world and has a strong genetic influence. The aim of this study was to examine the association of two known functional polymorphisms in the TGF-β inhibiting genes, asporin (ASPN) and cartilage intermediate layer protein (CILP), with hand OA and potential gene-occupational hand loading interaction. Results Statistically significant interaction of the CILP rs2073711 T and ASPN D15 alleles with hand OA was observed (OR = 2.48, 95% CI 1.27–4.85, p = 0.008) in a Finnish hand OA cohort of 543 women (aged 45–63). When stratified by variation in working tasks, low variation of working tasks increased the risk further (OR = 3.00, 95% CI 1.35–6.66, p = 0.007). Based on the analysis of ASPN and CILP protein-coding regions, functional studies were performed with one observed variant, rs41278695 in the ASPN gene. Analyses showed that bone morphogenetic protein 2 (BMP2) mediated expression of aggrecan (Agc1) and type II collagen (Col2a1) was significantly suppressed (p = 0.011 and p = 0.023, respectively) in a murine chondrocytic cell line (ATDC5) with cells stably expressing ASPN rs41278695. Conclusions The carriage of either ASPN D15 or CILP rs2073711 TT is associated with increased risk of symmetrical hand OA, particularly in individuals with low variation in work tasks. ASPN rs41278695 SNP had an effect on Agc1 and Col2a1 gene expression when induced with BMP-2 suggesting an effect on the cartilage extracellular matrix composition.
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Affiliation(s)
- Mari Taipale
- Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Aapistie 5, 90220, Oulu, Finland.,Biocenter Oulu and Faculty of Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
| | - Svetlana Solovieva
- Department of Epidemiology and Biostatistics, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland
| | - Päivi Leino-Arjas
- Department of Epidemiology and Biostatistics, Centre of Expertise for Health and Work Ability, Finnish Institute of Occupational Health, Helsinki, Finland
| | - Minna Männikkö
- Center for Life Course Health Research, Faculty of Medicine, University of Oulu, Aapistie 5, 90220, Oulu, Finland. .,Biocenter Oulu and Faculty of Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland.
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25
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Martínez-Campos C, Bahena-Román M, Torres-Poveda K, Burguete-García AI, Madrid-Marina V. TLR9 gene polymorphism -1486T/C (rs187084) is associated with uterine cervical neoplasm in Mexican female population. J Cancer Res Clin Oncol 2017; 143:2437-2445. [PMID: 28819773 DOI: 10.1007/s00432-017-2495-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2017] [Accepted: 08/07/2017] [Indexed: 02/06/2023]
Abstract
PURPOSE The aim of this work was to evaluate the association of single nucleotide polymorphisms in TLR9 (-1486 T/C [rs187084], -1237T/C [rs5743836] and G2848A [rs352140]) with HPV infection, squamous intraepithelial lesions, and uterine cervical neoplasm in a Mexican population. Additionally, the peripheral expression of TLR9 was evaluated to evaluate the differences in the TLR9 expression associated with every genotype in the locus -1486 of the TLR9 gene. The serum concentration of TLR9 was evaluated in a randomly selected subsample. METHODS Genotyping was performed using predesigned 5' endonuc lease assays and the association of the polymorphisms with the diagnosis groups were assessed by performing multinomial regression models. The relative expression of TLR9 in peripheral blood mononuclear cells was evaluated by real-time polymerase chain reaction and the association of the level of TLR9 expression with the diagnosis was evaluated by performing multinomial regression models. The serum concentration of TLR9 was evaluated in a subsample of patients diagnosed with uterine cervical neoplasm by ELISA. RESULTS The results showed that genotype TT in the -1486 locus of TLR9 was significantly associated with HPV infection (OR = 3.25, 95% CI 1.12-9.46), squamous intraepithelial cervical lesion (OR = 3.76, 95% CI 1.36-10.41), and uterine cervical neoplasm (OR = 5.30, 95% CI 1.81-15.55). Moreover, the highest level of TLR9 expression was significantly associated with a greater risk for developing squamous intraepithelial cervical lesion and uterine cervical neoplasm. The serum TLR9 concentration was higher in patients with uterine cervical cancer than in controls. CONCLUSION Our findings indicate that genotype TT in the -1486 locus of the TLR9 gene could comprise a risk genotype for HPV infection, squamous intraepithelial cervical lesion, and uterine cervical neoplasm in Mexican female population. Further studies with larger samples are needed to evaluate if the peripheral expression of TLR9 could be used as a biomarker of uterine cervical neoplasm progression.
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Affiliation(s)
- Cecilia Martínez-Campos
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
| | - Margarita Bahena-Román
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
| | - Kirvis Torres-Poveda
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
- CONACyT Research Fellow-Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico
| | - Ana I Burguete-García
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
| | - Vicente Madrid-Marina
- Dirección de Infecciones Crónicas y Cáncer, Centro de Investigación sobre Enfermedades Infecciosas, Instituto Nacional de Salud Pública, Cuernavaca, Morelos, Mexico.
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26
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Kordestanian N, Saadat M. A 50-bp Ins/Del polymorphism at the promoter region of the superoxide dismutase-1 and bipolar disorder type 1. Nord J Psychiatry 2017; 71:570-573. [PMID: 28750571 DOI: 10.1080/08039488.2017.1357754] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Bipolar disorder type 1 (BPD) is a chronic psychiatric illness and is associated with oxidative stress. Superoxide dismutase-1 (SOD1; OMIM: 147450) metabolizes highly reactive and more dangerous superoxide radicals into less reactive molecules. A functional 50-bp insertion/deletion (Ins/Del) polymorphism in the promoter region of the gene has been reported. The primary aim of the current case-control study was to explore whether the SOD1 Ins/Del polymorphism associated with the risk of BPD. A secondary aim was to investigate the association between the study polymorphism and age of onset of BPD. The present case-control study was performed in Shiraz (southern Iran) on 228 BPD and 224 healthy blood donor controls. The genotypes of the SOD1 Ins/Del polymorphism were determined by polymerase chain reaction. There was no significant association between the genotypes of Ins/Del polymorphism and the risk of BPD. Using Cox proportional hazards regression model, after adjustment for family history of BPD, revealed a significant association between the SOD1 Ins/Del polymorphism and age of onset. The age of onset was significantly lower for the Del/Del genotype than the 'Ins/Ins + Ins/Del' genotypes (hazard ratio = 2.33, 95%CI: 1.08-5.02, p = .030). Our present findings revealed that although the SOD1 Ins/Del polymorphism was not associated with the risk of BPD, it was significantly associated with age of onset of BPD.
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Affiliation(s)
- Nazanin Kordestanian
- a Department of Biology, College of Sciences , Shiraz University , Shiraz , Iran
| | - Mostafa Saadat
- a Department of Biology, College of Sciences , Shiraz University , Shiraz , Iran
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27
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Aghasadeghi F, Saadat M. Association between ABO and Rh Blood Groups and Risk of Preeclampsia: A Case-Control Study from Iran. Open Access Maced J Med Sci 2017; 5:173-176. [PMID: 28507623 PMCID: PMC5420769 DOI: 10.3889/oamjms.2017.002] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/03/2016] [Revised: 12/05/2016] [Accepted: 12/06/2016] [Indexed: 01/26/2023] Open
Abstract
AIM Preeclampsia (PE) is a major cause of maternal and neonatal morbidity and mortality. There is a genetic component in the development of PE with estimated heritability around 0.47. Several studies have investigated the association between maternal ABO blood groups (OMIM 110300) and risk of PE, with contradictory results have emerged. Considering that there is no study in this filed from Iranian population, the present case-control study was carried out at Shiraz (south-west Iran). MATERIAL AND METHODS In this study 331 women; 121 pregnant with PE and 210 normotensive pregnant women were included. Using blood group O (for ABO blood groups) or Rh+ (for Rh blood groups) as a reference, odds ratios (ORs) and its 95% confidence intervals (95% CI) of PE risk were estimated from logistic regression analysis. RESULTS Although the A (OR = 0.67, 95% CI = 0.39-1.17, P = 0.165), B (OR = 0.86, 95% CI = 0.48-1.53, P = 0.615) and AB (OR = 1.14, 95% CI = 0.37-3.45, P = 0.812) phenotypes showed lower risks compared with the O blood group, statistical analysis indicated that there was no significant association between ABO phenotypes and risk of PE. The frequency of Rh- phenotype was higher among PE patients compared with the control group. However, the association was not significant (OR = 1.79, 95% CI = 0.69-4.65, P = 0.229). Adjusted ORs for age of participants and parity did not change the above-mentioned associations. CONCLUSION Our present findings indicate that there is no association between ABO and Rh blood groups and risk of PE in Iranian population.
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Affiliation(s)
| | - Mostafa Saadat
- Department of Biology, College of Sciences, Shiraz University, Shiraz 71467-13565, Iran
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28
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Sanabria-Salas MC, Hernández-Suárez G, Umaña-Pérez A, Rawlik K, Tenesa A, Serrano-López ML, Sánchez de Gómez M, Rojas MP, Bravo LE, Albis R, Plata JL, Green H, Borgovan T, Li L, Majumdar S, Garai J, Lee E, Ashktorab H, Brim H, Li L, Margolin D, Fejerman L, Zabaleta J. IL1B-CGTC haplotype is associated with colorectal cancer in admixed individuals with increased African ancestry. Sci Rep 2017; 7:41920. [PMID: 28157220 PMCID: PMC5291207 DOI: 10.1038/srep41920] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2016] [Accepted: 01/03/2017] [Indexed: 02/07/2023] Open
Abstract
Single-nucleotide polymorphisms (SNPs) in cytokine genes can affect gene expression and thereby modulate inflammation and carcinogenesis. However, the data on the association between SNPs in the interleukin 1 beta gene (IL1B) and colorectal cancer (CRC) are conflicting. We found an association between a 4-SNP haplotype block of the IL1B (-3737C/-1464G/-511T/-31C) and CRC risk, and this association was exclusively observed in individuals with a higher proportion of African ancestry, such as individuals from the Coastal Colombian region (odds ratio, OR 2.06; 95% CI 1.31-3.25; p < 0.01). Moreover, a significant interaction between this CRC risk haplotype and local African ancestry dosage was identified in locus 2q14 (p = 0.03). We conclude that Colombian individuals with high African ancestry proportions at locus 2q14 harbour more IL1B-CGTC copies and are consequently at an increased risk of CRC. This haplotype has been previously found to increase the IL1B promoter activity and is the most frequent haplotype in African Americans. Despite of limitations in the number of samples and the lack of functional analysis to examine the effect of these haplotypes on CRC cell lines, our results suggest that inflammation and ethnicity play a major role in the modulation of CRC risk.
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Affiliation(s)
- María Carolina Sanabria-Salas
- Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia
- Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia
| | - Gustavo Hernández-Suárez
- Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia
| | - Adriana Umaña-Pérez
- Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia
| | - Konrad Rawlik
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK
| | - Albert Tenesa
- The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, UK
- MRC-Human Genetics Unit, University of Edinburgh, UK
| | - Martha Lucía Serrano-López
- Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia
- Departamento de Química, Universidad Nacional de Colombia, Bogotá D.C., Colombia
| | | | - Martha Patricia Rojas
- Subdirección de Investigaciones, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia
| | | | - Rosario Albis
- Servicio de Gastroenterología, Instituto Nacional de Cancerología de Colombia, Bogotá D.C., Colombia
| | | | | | | | - Li Li
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US
| | - Sumana Majumdar
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US
| | - Jone Garai
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US
| | - Edward Lee
- Department of Pathology & Cancer Center, Howard University College of Medicine, Washington, D.C., US
| | - Hassan Ashktorab
- Department of Pathology & Cancer Center, Howard University College of Medicine, Washington, D.C., US
| | - Hassan Brim
- Department of Pathology & Cancer Center, Howard University College of Medicine, Washington, D.C., US
| | - Li Li
- Ochsner Clinic Foundation, New Orleans, LA, US
| | | | - Laura Fejerman
- Department of Medicine, Division of General Internal Medicine, Institute for Human Genetics and Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, US
| | - Jovanny Zabaleta
- Stanley S. Scott Cancer Center, Louisiana State University Health Sciences Center, New Orleans, LA, US
- Department of Pediatrics, Louisiana State University Health Sciences Center, New Orleans, LA, US
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Wang H, Hua M, Wang S, Yu J, Chen C, Zhao X, Zhang C, Zhong C, Wang R, He N, Hou M, Ma D. Genetic polymorphisms of IL-18 rs1946518 and IL-1β rs16944 are associated with prognosis and survival of acute myeloid leukemia. Inflamm Res 2016; 66:249-258. [PMID: 27928589 DOI: 10.1007/s00011-016-1012-4] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2016] [Revised: 11/16/2016] [Accepted: 11/22/2016] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML. METHODS AND RESULTS We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB -94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival. CONCLUSION IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.
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Affiliation(s)
- Hong Wang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China.,Department of Hematology, Zibo Central Hospital, Zibo, Shandong, People's Republic of China
| | - Mingqiang Hua
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Shukang Wang
- Department of Epidemiology and Biostatistics, School of Public Health, Shandong University, Jinan, People's Republic of China
| | - Jie Yu
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chen Chen
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Xueyun Zhao
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chen Zhang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Chaoqin Zhong
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Ruiqing Wang
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Na He
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Ming Hou
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China
| | - Daoxin Ma
- Department of Hematology, Qilu Hospital, Shandong University, 107 West Wenhua Rd, Jinan, 250012, People's Republic of China.
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30
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Hugen S, Thomas RE, German AJ, Burgener IA, Mandigers PJJ. Gastric carcinoma in canines and humans, a review. Vet Comp Oncol 2016; 15:692-705. [PMID: 27549077 DOI: 10.1111/vco.12249] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2015] [Revised: 05/06/2016] [Accepted: 05/20/2016] [Indexed: 02/06/2023]
Abstract
Gastric carcinoma (GC) is the most common neoplasm in the stomach of dogs. Although incidence in the general population is reported to be low, breed-specific GC has a high incidence. Median age at presentation ranges from 8 to approximately 10 years. The disease is mostly located in the lesser curvature and antropyloric region of the stomach. Unfortunately, diagnosis is usually made when the disease is at an advanced stage and, therefore, prognosis is poor. Due to similarities in clinical presentation, diagnosis, histology and prognosis, canine GC may serve as a valuable model for human GC. Extensive pedigrees of canine gastric carcinoma cases could reveal insights for human gastric carcinoma. Putative species differences include the role of Helicobacter in pathogenesis, the wide array of genetic data and screening available for humans, and treatment protocols that are available for human GC.
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Affiliation(s)
- S Hugen
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - R E Thomas
- Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - A J German
- School of Veterinary Science, University of Liverpool, Neston, UK
| | - I A Burgener
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
| | - P J J Mandigers
- Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands
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Skierucha M, Milne ANA, Offerhaus GJA, Polkowski WP, Maciejewski R, Sitarz R. Molecular alterations in gastric cancer with special reference to the early-onset subtype. World J Gastroenterol 2016; 22:2460-2474. [PMID: 26937134 PMCID: PMC4768192 DOI: 10.3748/wjg.v22.i8.2460] [Citation(s) in RCA: 44] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2015] [Revised: 11/06/2015] [Accepted: 12/30/2015] [Indexed: 02/06/2023] Open
Abstract
Currently, gastric cancer (GC) is one of the most frequently diagnosed neoplasms, with a global burden of 723000 deaths in 2012. It is the third leading cause of cancer-related death worldwide. There are numerous possible factors that stimulate the pro-carcinogenic activity of important genes. These factors include genetic susceptibility expressed in a single-nucleotide polymorphism, various acquired mutations (chromosomal instability, microsatellite instability, somatic gene mutations, epigenetic alterations) and environmental circumstances (e.g., Helicobcter pylori infection, EBV infection, diet, and smoking). Most of the aforementioned pathways overlap, and authors agree that a clear-cut pathway for GC may not exist. Thus, the categorization of carcinogenic events is complicated. Lately, it has been claimed that research on early-onset gastric carcinoma (EOGC) and hereditary GC may contribute towards unravelling some part of the mystery of the GC molecular pattern because young patients are less exposed to environmental carcinogens and because carcinogenesis in this setting may be more dependent on genetic factors. The comparison of various aspects that differ and coexist in EOGCs and conventional GCs might enable scientists to: distinguish which features in the pathway of gastric carcinogenesis are modifiable, discover specific GC markers and identify a specific target. This review provides a summary of the data published thus far concerning the molecular characteristics of GC and highlights the outstanding features of EOGC.
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Abstract
Viral and bacterial infections are involved in the development of human cancers, such as liver, nasopharyngeal, cervical, head and neck, and gastric cancers. Aberrant DNA methylation is frequently present in these cancers, and some of the aberrantly methylated genes are causally involved in cancer development and progression. Notably, aberrant DNA methylation can be present even in non-cancerous or precancerous tissues, and its levels correlate with the risk of cancer development, producing a so-called 'epigenetic field for cancerization'. Mechanistically, most viral or bacterial infections induce DNA methylation indirectly via chronic inflammation, but recent studies have indicated that some viruses have direct effects on the epigenetic machinery of host cells. From a translational viewpoint, a recent multicenter prospective cohort study demonstrated that assessment of the extent of alterations in DNA methylation in non-cancerous tissues can be used to predict cancer risk. Furthermore, suppression of aberrant DNA methylation was shown to be a useful strategy for cancer prevention in an animal model. Here, we review the involvement of aberrant DNA methylation in various types of infection-associated cancers, along with individual induction mechanisms, and we discuss the application of these findings for cancer prevention, diagnosis, and therapy.
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Affiliation(s)
- Naoko Hattori
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan
| | - Toshikazu Ushijima
- Division of Epigenomics, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
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Figura N, Marano L, Moretti E, Ponzetto A. Helicobacter pylori infection and gastric carcinoma: Not all the strains and patients are alike. World J Gastrointest Oncol 2016; 8:40-54. [PMID: 26798436 PMCID: PMC4714145 DOI: 10.4251/wjgo.v8.i1.40] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2015] [Revised: 10/06/2015] [Accepted: 11/03/2015] [Indexed: 02/05/2023] Open
Abstract
Gastric carcinoma (GC) develops in only 1%-3% of Helicobacter pylori (H. pylori) infected people. The role in GC formation of the bacterial genotypes, gene polymorphisms and host's factors may therefore be important. The risk of GC is enhanced when individuals are infected by strains expressing the oncoprotein CagA, in particular if CagA has a high number of repeats containing the EPIYA sequence in its C'-terminal variable region or particular amino acid sequences flank the EPIYA motifs. H. pylori infection triggers an inflammatory response characterised by an increased secretion of some chemokines by immunocytes and colonised gastric epithelial cells; these molecules are especially constituted by proteins composing the interleukin-1beta (IL-1β) group and tumour necrosis factor-alpha (TNF-α). Polymorphisms in the promoter regions of genes encoding these molecules, could account for high concentrations of IL-1β and TNF-α in the gastric mucosa, which may cause hypochlorhydria and eventually GC. Inconsistent results have been attained with other haplotypes of inflammatory and anti-inflammatory cytokines. Genomic mechanisms of GC development are mainly based on chromosomal or microsatellite instability (MSI) and deregulation of signalling transduction pathways. H. pylori infection may induce DNA instability and breaks of double-strand DNA in gastric mucocytes. Different H. pylori strains seem to differently increase the risk of cancer development run by the host. Certain H. pylori genotypes (such as the cagA positive) induce high degrees of chronic inflammation and determine an increase of mutagenesis rate, oxidative-stress, mismatch repair mechanisms, down-regulation of base excision and genetic instability, as well as generation of reactive oxygen species that modulate apoptosis; these phenomena may end to trigger or concur to GC development.
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Saify K, Saadat M. Susceptibility to methamphetamine dependence associated with high transcriptional activity alleles of VNTR polymorphism in the promoter region of monoamine oxidase A (MAOA). EGYPTIAN JOURNAL OF MEDICAL HUMAN GENETICS 2016. [DOI: 10.1016/j.ejmhg.2015.08.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022] Open
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Di Ciaula A. Increased deaths from gastric cancer in communities living close to waste landfills. INTERNATIONAL JOURNAL OF ENVIRONMENTAL HEALTH RESEARCH 2015; 26:281-290. [PMID: 26540187 DOI: 10.1080/09603123.2015.1109069] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Municipal waste landfills (MWLs) have been linked with some malignancies, but data about gastric cancer (GC) are still uncertain. METHODS Number of deaths from GC, death rates, and odds ratios (ORs) were calculated considering all residents in the 258 towns in the Apulia Region (4,099,547 subjects, years 2006-2009), living within 3 km from each of the 16 regional MWLs (n = 716,404) or in control areas (n = 3,383,143). RESULTS Males living close to MWLs showed a higher death rate for GC, a twofold higher mean number of GC deaths and higher adjusted ORs of GC, compared with controls areas. CONCLUSIONS In a large population and over a wide time period, an increased risk of death from GC has been shown in males living in communities close to MWLs. Primary prevention policies acting through more sustainable waste management might probably partially reduce deaths from GC in areas with MWLs.
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Affiliation(s)
- Agostino Di Ciaula
- a Division of Internal Medicine, Hospital of Bisceglie (BAT) Italy ; International Society of Doctors for Environment (ISDE) , Arezzo , Italy
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Tan P, Yeoh KG. Genetics and Molecular Pathogenesis of Gastric Adenocarcinoma. Gastroenterology 2015; 149:1153-1162.e3. [PMID: 26073375 DOI: 10.1053/j.gastro.2015.05.059] [Citation(s) in RCA: 357] [Impact Index Per Article: 35.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2015] [Revised: 05/18/2015] [Accepted: 05/20/2015] [Indexed: 02/07/2023]
Abstract
Gastric cancer (GC) is globally the fifth most common cancer and third leading cause of cancer death. A complex disease arising from the interaction of environmental and host-associated factors, key contributors to GC's high mortality include its silent nature, late clinical presentation, and underlying biological and genetic heterogeneity. Achieving a detailed molecular understanding of the various genomic aberrations associated with GC will be critical to improving patient outcomes. The recent years has seen considerable progress in deciphering the genomic landscape of GC, identifying new molecular components such as ARID1A and RHOA, cellular pathways, and tissue populations associated with gastric malignancy and progression. The Cancer Genome Atlas (TCGA) project is a landmark in the molecular characterization of GC. Key challenges for the future will involve the translation of these molecular findings to clinical utility, by enabling novel strategies for early GC detection, and precision therapies for individual GC patients.
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Affiliation(s)
- Patrick Tan
- Cancer and Stem Cell Biology Program, Duke-National University of Singapore Graduate Medical School, Singapore; Genome Institute of Singapore, Agency for Science, Technology, and Research, Singapore; Cancer Science Institute of Singapore, National University of Singapore, Singapore; Cellular and Molecular Research, National Cancer Centre Singapore, Singapore; Singapore Gastric Cancer Consortium, Singapore.
| | - Khay-Guan Yeoh
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore; Department of Gastroenterology and Hepatology, National University Health System, Singapore; Singapore Gastric Cancer Consortium, Singapore.
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Pabalan N, Jarjanazi H, Ozcelik H. Associations of the Insertion/Deletion Polymorphism in the ACE Gene and Risk of Gastric Cancer: A Meta-Analysis. J Gastrointest Cancer 2015; 46:370-9. [PMID: 26307111 DOI: 10.1007/s12029-015-9754-8] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
BACKGROUND Reported associations of ACE polymorphisms with gastric cancer have been inconsistent, prompting a meta-analysis of 12 published case-control studies where we estimated risk (odds ratio [OR]). METHODS We searched MEDLINE through PubMed and EMBASE for suitable articles that had case-control design with gastric cancer as outcome. In this meta-analysis, our overall findings were subjected to modifier analyses (outlier and sensitivity treatments). We also performed subgroup analysis based on ethnicity (German and Japanese) and histological subtype (intestinal and diffuse). RESULTS Significance of the protective effects among homozygote carriers of the II genotype (OR 0.54-0.63, P = 0.01-0.02) disappeared with outlier analysis (OR 0.81-0.88, P = 0.12-0.14). Among DD homozygotes, this treatment altered the direction of association from weak protection (OR 0.95-0.96, P = 0.79-0.82) to increased risk (OR 1.13-1.19, P = 0.14-0.16). No significant associations were observed among ID genotype carriers (OR 0.91-0.94, P = 0.69-0.72). Japanese pooled effects varied across the genotype comparisons (OR 0.93-1.06, P = 0.54-0.72). Sensitivity treatment demonstrated robustness of the II genotype, but not the other two, both in overall and subgroup analyses. Histological subtype analysis yielded protection from intestinal cancer across the comparisons (OR 0.38-0.71, P = 0.15-0.50) but variable results for the diffuse type (OR 0.59-1.32, P = 0.19-0.92). CONCLUSION In summary, carriers of the ACE II genotype appear to be protected from gastric cancer, regardless of ethnicity or tumor type.
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Affiliation(s)
- Noel Pabalan
- Center for Research and Development, Angeles University Foundation, 2009, Angeles City, Philippines
| | - Hamdi Jarjanazi
- Environmental Monitoring and Reporting Branch, Ontario Ministry of the Environment and Climate Change, 125 Resources Road, Toronto, ON, M9P 3V6, Canada.
| | - Hilmi Ozcelik
- Fred A. Litwin Centre for Cancer Genetics, Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 60 Murray St. Room L6-303, Box 29, Toronto, ON, M5T 3L9, Canada
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Mocellin S, Verdi D, Pooley KA, Nitti D. Genetic variation and gastric cancer risk: a field synopsis and meta-analysis. Gut 2015; 64:1209-19. [PMID: 25731870 DOI: 10.1136/gutjnl-2015-309168] [Citation(s) in RCA: 135] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Accepted: 02/06/2015] [Indexed: 12/19/2022]
Abstract
BACKGROUND Data on genetic susceptibility to sporadic gastric carcinoma have been published at a growing pace, but to date no comprehensive overview and quantitative summary has been available. METHODS We conducted a systematic review and meta-analysis of the evidence on the association between DNA variation and risk of developing stomach cancer. To assess result credibility, summary evidence was graded according to the Venice criteria and false positive report probability (FPRP) was calculated to further validate result noteworthiness. Meta-analysis was also conducted for subgroups, which were defined by ethnicity (Asian vs Caucasian), tumour histology (intestinal vs diffuse), tumour site (cardia vs non-cardia) and Helicobacter pylori infection status (positive vs negative). RESULTS Literature search identified 824 eligible studies comprising 2 530 706 subjects (cases: 261 386 (10.3%)) and investigating 2841 polymorphisms involving 952 distinct genes. Overall, we performed 456 primary and subgroup meta-analyses on 156 variants involving 101 genes. We identified 11 variants significantly associated with disease risk and assessed to have a high level of summary evidence: MUC1 rs2070803 at 1q22 (diffuse carcinoma subgroup), MTX1 rs2075570 at 1q22 (diffuse), PSCA rs2294008 at 8q24.2 (non-cardia), PRKAA1 rs13361707 5p13 (non-cardia), PLCE1 rs2274223 10q23 (cardia), TGFBR2 rs3087465 3p22 (Asian), PKLR rs3762272 1q22 (diffuse), PSCA rs2976392 (intestinal), GSTP1 rs1695 11q13 (Asian), CASP8 rs3834129 2q33 (mixed) and TNF rs1799724 6p21.3 (mixed), with the first nine variants characterised by a low FPRP. We also identified polymorphisms with lower quality significant associations (n=110). CONCLUSIONS We have identified several high-quality biomarkers of gastric cancer susceptibility. These data will form the backbone of an annually updated online resource that will be integral to the study of gastric carcinoma genetics and may inform future screening programmes.
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Affiliation(s)
- Simone Mocellin
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Daunia Verdi
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Karen A Pooley
- Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge, UK
| | - Donato Nitti
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
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RAD51 G135C genetic polymorphism and their potential role in gastric cancer induced by Helicobacter pylori infection in Bhutan. Epidemiol Infect 2015; 144:234-40. [PMID: 26119522 DOI: 10.1017/s0950268815001430] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
In order to evaluate the role of the RAD51 G135C genetic polymorphism on the risk of gastric cancer induced by Helicobacter pylori infection, we determined allele frequency and genotype distribution of this polymorphism in Bhutan--a population documented with high prevalence of gastric cancer and extremely high prevalence of H. pylori infection. The status of RAD51 G135C was examined by restriction fragment length polymorphism analysis of PCR amplified fragments and sequencing. Histological scores were evaluated according to the updated Sydney system. G135C carriers showed significantly higher scores for intestinal metaplasia in the antrum than G135G carriers [mean (median) 0·33 (0) vs. 0·08 (0), P = 0·008]. Higher scores for intestinal metaplasia of G135C carriers compared to those of G135G carriers were also observed in H. pylori-positive patients [0·3 (0) vs. 0·1 (0), P = 0·002] and H. pylori-positive patients with gastritis [0·4 (0) vs. 0·1 (0), P = 0·002] but were not found in H. pylori-negative patients. Our findings revealed that a combination of H. pylori infection and RAD51 G135C genotype of the host showed an increasing score for intestinal metaplasia. Therefore, RAD51 G135C might be the important predictor for gastric cancer of H. pylori-infected patients.
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40
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Zhou CJ, Zhang LW, Gao F, Zhang B, Wang Y, Chen DF, Jia YB. Association analysis of common genetic variations in MUC5AC gene with the risk of non-cardia gastric cancer in a Chinese population. Asian Pac J Cancer Prev 2015; 15:4207-10. [PMID: 24935372 DOI: 10.7314/apjcp.2014.15.10.4207] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/10/2022] Open
Abstract
Several lines of evidence suggest that genetic variation in MUC5AC gene might contribute to the risk of gastric cancer. We conducted a case-control study to evaluate the relationship between common genetic variations in MUC5AC gene and non-cardia gastric cancer using an LD-based tagSNP approach in Baotou, north-western China. We genotyped 12 tagSNPs by TaqMan method among 288 cases with non-cardia gastric cancer and 281 normal controls. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for non-cardia gastric cancer risk in association with alleles, genotypes and haplotypes. We observed that the frequencies of rs3793964 C allele and rs11040869 A allele were significantly lower in cases than in controls. Meanwhile, minor allele homozygotes of rs3793964 and rs11040869 were significantly associated with a decreased risk of non-cardia gastric cancer when compared with their major allele homozygotes. Furthermore, a statistically significantly protective effect of rs885454 genotypes on non-cardia gastric cancer was also observed (for CT vs. CC: OR=0.581, 95%CI=0.408-0.829; for CT/TT vs. CC: OR=0.623, 95%CI=0.451-0.884). Our results indicated that some common genetic variations in the MUC5AC gene might have effects on the risk of non-cardia gastric cancer in our studied population.
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Affiliation(s)
- Cheng-Jiang Zhou
- School of Basic Medicine, Baotou Medical College, Baotou, China E-mail :
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Wei XL, Qiu MZ, Jin Y, Huang YX, Wang RY, Chen WW, Wang DS, Wang F, Luo HY, Zhang DS, Wang FH, Li YH, Xu RH. Hepatitis B virus infection is associated with gastric cancer in China: an endemic area of both diseases. Br J Cancer 2015; 112:1283-90. [PMID: 25695484 PMCID: PMC4385949 DOI: 10.1038/bjc.2014.406] [Citation(s) in RCA: 45] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2014] [Revised: 06/17/2014] [Accepted: 06/22/2014] [Indexed: 02/07/2023] Open
Abstract
Background: Hepatitis B virus (HBV) infection was demonstrated to be a risk factor of several cancers of the digestive system. In addition, liver cirrhosis, which could possibly result from chronic HBV infection, was associated with a higher risk of gastric cancer. However, the association of HBV infection and gastric cancer has not been investigated. Methods: A retrospective case–control study with 580 cases and 580 controls matched for age, sex and year of diagnosis was conducted. The associations between gastric cancer and HBV infection were explored with univariate and multivariate unconditional logistic regression analysis. Results: Hepatitis B surface antigen (HBsAg) was positively associated with gastric cancer (AOR (95% CI): 1.49 (1.06–2.10)). This association remained significant in patients without family history of gastric cancer (AOR (95% CI): (1.06–2.11)). For HBsAg-negative population, being anti-HBc positive/anti-HBs negative, which possibly indicated occult HBV infection, was also found to have some associations with gastric cancer. In addition, some synergistic effects between HBV infection and blood type A in gastric cancer were identified. Conclusions: The HBV infection was positively related with gastric cancer, especially for patients without family history of gastric cancer. Further prospective studies are warranted to confirm this relationship.
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Affiliation(s)
- X-L Wei
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - M-Z Qiu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - Y Jin
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - Y-X Huang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - R-Y Wang
- Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China
| | - W-W Chen
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - D-S Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - F Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - H-Y Luo
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - D-S Zhang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - F-H Wang
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - Y-H Li
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
| | - R-H Xu
- Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 651 Dongfeng Road East, Guangzhou 510060, China
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Belbasis L, Panagiotou OA, Dosis V, Evangelou E. A systematic appraisal of field synopses in genetic epidemiology: a HuGE review. Am J Epidemiol 2015; 181:1-16. [PMID: 25504025 DOI: 10.1093/aje/kwu249] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Evidence from genetic association studies is accumulating rapidly. Field synopses have recently arisen as an unbiased way of systematically synthesizing this evidence. We performed a systematic review and appraisal of published field synopses in genetic epidemiology and assessed their main findings and methodological characteristics. We identified 61 eligible field synopses, published between January 1, 2007, and October 31, 2013, on 52 outcomes reporting 734 significant associations at the P < 0.05 level. The median odds ratio for these associations was 1.25 (interquartile range, 1.15-1.43). Egger's test was the most common method (n = 30 synopses) of assessing publication bias. Only 12 synopses (20%) used the Venice criteria to evaluate the epidemiologic credibility of their findings (n = 449 variants). Eleven synopses (18%) were accompanied by an online database that has been regularly updated. These synopses received more citations (P = 0.01) and needed a larger research team (P = 0.02) than synopses without an online database. Overall, field synopses are becoming a valuable tool for the identification of common genetic variants, especially when researchers follow relevant methodological guidelines. Our work provides a summary of the current status of the field synopses published to date and may help interested readers efficiently identify the online resources containing the relevant genetic evidence.
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Hirbod-Mobarakeh A, Amirzargar AA, Nikbin B, Nicknam MH, Kutikhin A, Rezaei N. Immunogenetics of Cancer. CANCER IMMUNOLOGY 2015:295-341. [DOI: 10.1007/978-3-662-44006-3_17] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/04/2025]
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Espinosa-Parrilla Y, Muñoz X, Bonet C, Garcia N, Venceslá A, Yiannakouris N, Naccarati A, Sieri S, Panico S, Huerta JM, Barricarte A, Menéndez V, Sánchez-Cantalejo E, Dorronsoro M, Brennan P, Duarte-Salles T, B As Bueno-de-Mesquita H, Weiderpass E, Lund E, Clavel-Chapelon F, Boutron-Ruault MC, Racine A, Numans ME, Tumino R, Canzian F, Campa D, Sund M, Johansson M, Ohlsson B, Lindkvist B, Overvad K, Tjønneland A, Palli D, Travis RC, Khaw KT, Wareham N, Boeing H, Nesi G, Riboli E, Gonzalez CA, Sala N. Genetic association of gastric cancer with miRNA clusters including the cancer-related genes MIR29, MIR25, MIR93 and MIR106: results from the EPIC-EURGAST study. Int J Cancer 2014; 135:2065-76. [PMID: 24643999 DOI: 10.1002/ijc.28850] [Citation(s) in RCA: 46] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 01/24/2014] [Accepted: 01/28/2014] [Indexed: 12/12/2022]
Abstract
MicroRNAs (miRNAs) are post-transcriptional gene regulators involved in a wide range of biological processes including tumorigenesis. Deregulation of miRNA pathways has been associated with cancer but the contribution of their genetic variability to this disorder is poorly known. We analyzed the genetic association of gastric cancer (GC) and its anatomical and histological subtypes, with 133 single-nucleotide polymorphisms (SNPs) tagging 15 isolated miRNAs and 24 miRNA clusters potentially involved in cancer, in 365 GC cases and 1,284 matched controls within the European Prospective Investigation into Cancer and Nutrition cohort. Various SNPs were associated with GC under the log-additive model. Furthermore, several of these miRNAs passed the gene-based permutation test when analyzed according to GC subtypes: three tagSNPs of the miR-29a/miR-29b-1 cluster were associated with diffuse subtype (minimum p-value = 1.7 × 10(-4) ; odds ratio, OR = 1.72; 95% confidence interval, CI = 1.30-2.28), two tagSNPs of the miR-25/miR-93/miR-106b cluster were associated with cardia GC (minimum p-value = 5.38 × 10(-3) ; OR = 0.56, 95% CI = 0.37-0.86) and one tagSNP of the miR-363/miR-92a-2/miR-19b-2/miR-20b/miR-18b/miR-106a cluster was associated with noncardia GC (minimum p-value = 5.40 × 10(-3) ; OR = 1.41, 95% CI = 1.12-1.78). Some functionally validated target genes of these miRNAs are implicated in cancer-related processes such as methylation (DNMT3A, DNMT3B), cell cycle (E2F1, CDKN1A, CDKN1C), apoptosis (BCL2L11, MCL1), angiogenesis (VEGFA) and progression (PIK3R1, MYCN). Furthermore, we identified genetic interactions between variants tagging these miRNAs and variants in their validated target genes. Deregulation of the expression of these miRNAs in GC also supports our findings, altogether suggesting for the fist time that genetic variation in MIR29, MIR25, MIR93 and MIR106b may have a critical role in genetic susceptibility to GC and could contribute to the molecular mechanisms of gastric carcinogenesis.
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Affiliation(s)
- Yolanda Espinosa-Parrilla
- Institut de Biologia Evolutiva, CSIC-Universitat Pompeu Fabra, Departament de Ciències Experimentals i de la Salut, UPF, Barcelona, Spain; Programa de Genética Humana, ICBM, Facultad de Medicina, Universidad de Chile, Santiago de Chile, Chile
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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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Jing H, Dai F, Zhao C, Yang J, Li L, Kota P, Mao L, Xiang K, Zheng C, Yang J. Association of genetic variants in and promoter hypermethylation of CDH1 with gastric cancer: a meta-analysis. Medicine (Baltimore) 2014; 93:e107. [PMID: 25340495 PMCID: PMC4616322 DOI: 10.1097/md.0000000000000107] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Gastric cancer (GC) is a common cause of cancer-related death. The etiology and pathogenesis of GC remain unclear, with genetic and epigenetic factors playing an important role. Previous studies investigated the association of GC with many genetic variants in and promoter hypermethylation of E-cadherin gene (CDH1), with conflicting results reported.To clarify this inconsistency, we conducted updated meta-analyses to assess the association of genetic variants in and the promoter hypermethylation of CDH1 with GC, including C-160A (rs16260) and other less-studied genetic variants,Data sources were PubMed, Cochrane Library, Google Scholar, Web of Knowledge, and HuGE, a navigator for human genome epidemiology.Study eligibility criteria and participant details are as follows: studies were conducted on human subjects; outcomes of interest include GC; report of genotype data of individual genetic variants in (or methylation status of) CDH1 in participants with and without GC (or providing odds ratios [OR] and their variances).Study appraisal and synthesis methods included the use of OR as a measure of the association, calculated from random effects models in meta-analyses. We used I for the assessment of between-study heterogeneity, and publication bias was assessed using funnel plot and Egger test.A total of 33 studies from 30 published articles met the eligibility criteria and were included in our analyses. We found no association between C-160A and GC (OR = 0.88; 95% confidence interval [CI], 0.71-1.08; P = 0.215), assuming an additive model (reference allele C). C-160A was associated with cardia (OR = 0.21; 95% CI, 0.11-0.41; P = 2.60 × 10), intestinal (OR = 0.66; 95% CI, 0.49-0.90; P = 0.008), and diffuse GC (OR = 0.57; 95% CI, 0.40-0.82; P = 0.002). The association of C-160A with noncardia GC is of bottom line significance (OR = 0.65; 95% CI, 0.42-1.01; P = 0.054). Multiple other less-studied genetic variants in CDH1 also exhibited association with GC. Gene-based analysis indicated a significant cumulative association of genetic variants in CDH1 with GC (all Ps <10). Sensitivity analysis excluding studies not meeting Hardy-Weinberg equilibrium (HWE) yielded similar results. Analysis by ethnic groups revealed significant association of C-160A with cardia GC in both Asian and whites, significant association with noncardia GC only in Asians, and no significant association with intestinal GC in both ethnic groups. There was significant association of C160-A with diffuse GC in Asians (P = 0.011) but not in whites (P = 0.081). However, after excluding studies that violate HWE, this observed association is no longer significant (P = 0.126). We observed strong association of promoter hypermethylation of CDH1 with GC (OR = 12.23; 95% CI, 8.80-17.00; P = 1.42 × 10), suggesting that epigenetic regulation of CDH1 could play a critical role in the etiology of GC.Limitations of this study are as follows: we could not adjust for confounding factors; some meta-analyses were based on a small number of studies; sensitivity analysis was limited due to unavailability of data; we could not test publication bias for some meta-analyses due to small number of included studies.We found no significant association of the widely studied genetic variant C-160A, but identified some other genetic variants showing significant association with GC. Future studies with large sample sizes that control for confounding risk factors and/or intensively interrogate CpG sites in CDH1 are needed to validate the results found in this study and to explore additional epigenetic loci that affect GC risk.
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Affiliation(s)
- Huiquan Jing
- Institute of Social Science Survey (HJ), Peking University, Beijing; Department of Social Science (HJ), Shenyang Medical College; Emergency Department (LL); Department of Gastroenterology (CZ), Shengjing Hospital, China Medical University, Shenyang, Liaoning; Division of Gastroenterology (FD, JY, LM), Second Affiliated Hospital, Medical College of Xi'an Jiaotong University, Xi'an, Shaanxi; Department of General Surgery (KX), Third Xiangya Hospital, Central South University, Changsha, Hunan, China; Brain Tumor Center (CZ), Cancer and Blood Diseases Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH; Department of Biostatistics and Epidemiology (PK), University of Oklahoma Health Sciences Center, Oklahoma City, OK; Rush Alzheimer's Disease Center (JYY); and Department of Neurological Sciences (JYY), Rush University Medical Center, Chicago, IL
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Pinheiro DDR, Ferreira WAS, Barros MBL, Araújo MD, Rodrigues-Antunes S, Borges BDN. Perspectives on new biomarkers in gastric cancer: Diagnostic and prognostic applications. World J Gastroenterol 2014; 20:11574-11585. [PMID: 25206265 PMCID: PMC4155351 DOI: 10.3748/wjg.v20.i33.11574] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/22/2013] [Revised: 03/14/2014] [Accepted: 05/05/2014] [Indexed: 02/06/2023] Open
Abstract
Gastric cancer is considered one of the most deadly tumors worldwide. Even with the decline in its incidence, the mortality rate of this disease has remained high, mainly due to its late diagnosis and to the lack of precise prognostic markers. The main purpose of this review is to present genetic, epigenetic and proteomic molecular markers that may be used in a diagnostic and prognostic manner and to discuss the pros and cons of each type of marker for improving clinical practice. In this sense, we observed that the use of genetic markers, especially mutations and polymorphisms, should be carefully considered, as they are strongly affected by ethnicity. Proteomic-based markers show promise, but the higher costs of the associated techniques continue to make this approach expensive for routine use. Alternatively, epigenetic markers appear to be very promising, as they can be detected in bodily fluids as well as tissues. However, such markers must be used carefully because epigenetic changes may occur due to environmental factors and aging. Despite the advances in technology and its access, to date, there are few defined biomarkers of prognostic and diagnostic use for gastric tumors. Therefore, the use of a panel of several approaches (genetic, epigenetic and proteomic) should be considered the best alternative for clinical practice.
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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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Chiurillo MA. Role of gene polymorphisms in gastric cancer and its precursor lesions: Current knowledge and perspectives in Latin American countries. World J Gastroenterol 2014; 20:4503-4515. [PMID: 24782603 PMCID: PMC4000487 DOI: 10.3748/wjg.v20.i16.4503] [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: 10/29/2013] [Revised: 12/23/2013] [Accepted: 03/13/2014] [Indexed: 02/07/2023] Open
Abstract
Latin America shows one of the highest incidence rates of gastric cancer in the world, with variations in mortality rates among nations or even within countries belonging to this region. Gastric cancer is the result of a multifactorial complex process, for which a multistep model of carcinogenesis is currently accepted. Additionally to the infection with Helicobacter pylori, that plays a major role, environmental factors as well as genetic susceptibility factors are significant players at different stages in the gastric cancer process. The differences in population origin, demographic structure, socio-economic development, and the impact of globalization lifestyles experienced in Latin America in the last decades, all together offer opportunities for studying in this context the influence of genetic polymorphisms in the susceptibility to gastric cancer. The aim of this article is to discuss current trends on gastric cancer in Latin American countries and to review the available published information about studies of association of gene polymorphisms involved in gastric cancer susceptibility from this region of the world. A total of 40 genes or genomic regions and 69 genetic variants, 58% representing markers involved in inflammatory response, have been used in a number of studies in which predominates a low number of individuals (cases and controls) included. Polymorphisms of IL-1B (-511 C/T, 14 studies; -31 T/C, 10 studies) and IL-1RN (variable number of tandem repeats, 17 studies) are the most represented ones in the reviewed studies. Other genetic variants recently evaluated in large meta-analyses and associated with gastric cancer risk were also analyzed in a few studies [e.g., prostate stem cell antigen (PSCA), CDH1, Survivin]. Further and better analysis centered in gene polymorphisms linked to other covariates, epidemiological studies and the information provided by meta-analyses and genome-wide association studies should help to improve our understanding of gastric cancer etiology in order to develop appropriate health programs in Latin America.
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50
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Pan XF, Wen Y, Loh M, Wen YY, Yang SJ, Zhao ZM, Tian Z, Huang H, Lan H, Chen F, Soong R, Yang CX. Interleukin-4 and -8 gene polymorphisms and risk of gastric cancer in a population in Southwestern China. Asian Pac J Cancer Prev 2014; 15:2951-2957. [PMID: 24815430 DOI: 10.7314/apjcp.2014.15.7.2951] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2025] Open
Abstract
BACKGROUND Gastric carcinogenesis is a complicated process that involves environmental and genetic factors like interleukin-4 (IL-4) and IL-8. Single nucleotide polymorphisms in their genes are associated with changed levels of gene expression. Here, we investigated the association between IL4-590 C>T and IL8-251T>A and gastric cancer (GC) risk in Sichuan of Southwestern China. MATERIALS AND METHODS We surveyed the research subjects using a self-designed questionnaire with questions on demographic factors and putative risk factors. Approximately 2-5ml of whole blood was collected after field survey to analyze IL4-590 C>T and IL8-251T>A genotypes using MALDI-TOF MS. RESULTS Our study recruited 308 pairs of GC patients and controls, including 224 (72.7%) men and 84 (27.3%) women in each group. There were 99 cardia and 176 noncardia GC patients in the case group. The case and control groups had an average age of 57.7±10.6 (mean±SD) and 57.6±11.1 years. GC patients reported a significantly greater proportion of family history of cancer (29.9% vs 10.7%, p<0.01) and drinking (54.6% vs 43.2%, p<0.01) than did controls. Variant genotypes of IL-4-590 C>T and IL-8-251 T>A were not associated with overall GC risk (adjusted OR, 0.89; 95%CI, 0.61-1.28 for CT or CC vs TT; adjusted OR, 1.14; 95%CI, 0.86-1.79 for TA or AA vs TT). Stratification analysis of two SNPs for risk by subsites only found that variant IL-8-251 TA or AA genotype was associated with increased noncardia GC risk (adjusted OR, 2.58; 95%CI, 1.19-5.57). We did not observe interactions between the IL-8-251 T>A genotype and smoking (adjusted OR, 0.38; 95%CI, 0.08-1.79) or drinking (adjusted OR, 0.36; 95%CI, 0.08-1.65) for risk of noncardia GC. CONCLUSIONS Our data indicate no association between the two SNPs of IL-4-590 and IL-8-251 with overall GC risk, while the IL-8-251 TA or AA genotype conferred risk of cardia GC. Our findings contribute to the evidence body for risk of SNPs associated with the development of gastric cancer in this region.
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Affiliation(s)
- Xiong-Fei Pan
- Department of Epidemiology, West China School of Public Health, Sichuan University, Chengdu, China E-mail :
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