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      Genetic polymorphisms and gastric cancer risk: a comprehensive review synopsis from meta-analysis and genome-wide association studies

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          Abstract

          Objective

          In the past few decades, more than 500 reports have been published on the relationship between single nucleotide polymorphisms (SNPs) on candidate genes and gastric cancer (GC) risk. Previous findings have been disputed and are controversial. Therefore, we performed this article to summarize and assess the credibility and strength of genetic polymorphisms on the risk of GC.

          Methods

          We used Web of Science, PubMed, and Medline to identify meta-analyses published before July 30th, 2018 that assessed associations between variants on candidate genes and the risk of GC. Cumulative epidemiological evidence of statistical associations was assessed combining Venice criteria and a false-positive report probability (FPRP) test.

          Results

          Sixty-one variants demonstrated a significant association with GC risk, whereas 29 demonstrated no association. Nine variants on nine genes were rated as presenting strong cumulative epidemiological evidence for a nominally significant association with GC risk, including APE1 (rs1760944), DNMT1 (rs16999593), ERCC5 (rs751402), GSTT1 (null/presence), MDM2 (rs2278744), PPARG (rs1801282), TLR4 (rs4986790), IL-17F (rs763780), and CASP8 (rs3834129). Eleven SNPs were rated as moderate, and 33 SNPs were rated as weak. We also used the FPRP test to identify 13 noteworthy SNPs in five genome-wide association studies.

          Conclusions

          Sixty-one variants are significantly associated with GC risk, and 29 variants are not associated with GC risk; however, five variants on five genes presented strong evidence for an association upgraded from moderate. Further study of these variants may be needed in the future. Our study also provides referenced information for the genetic predisposition to GC.

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          Chapter 11: Genome-Wide Association Studies

          Genome-wide association studies (GWAS) have evolved over the last ten years into a powerful tool for investigating the genetic architecture of human disease. In this work, we review the key concepts underlying GWAS, including the architecture of common diseases, the structure of common human genetic variation, technologies for capturing genetic information, study designs, and the statistical methods used for data analysis. We also look forward to the future beyond GWAS.
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            Genome-wide association studies of gastric adenocarcinoma and esophageal squamous cell carcinoma identify a shared susceptibility locus in PLCE1 at 10q23

            We conducted a genome-wide association study of gastric cancer (GC) and esophageal squamous cell carcinoma (ESCC) in ethnic Chinese subjects in which we genotyped 551,152 single nucleotide polymorphisms (SNPs). We report a combined analysis of 2,240 GC cases, 2,115 ESCC cases, and 3,302 controls drawn from five studies. In logistic regression models adjusted for age, sex, and study, multiple variants at 10q23 had genome-wide significance for GC and ESCC independently. A notable signal was rs2274223, a nonsynonymous SNP located in PLCE1, for GC (P=8.40×10−9; per allele odds ratio (OR) = 1.31) and ESCC (P=3.85×10−9; OR = 1.34). The association with GC differed by anatomic subsite. For tumors located in the cardia the association was stronger (P=4.19 × 10−15; OR= 1.57) and for those located in the noncardia stomach it was absent (P=0.44; OR=1.05). Our findings at 10q23 could provide insight into the high incidence rates of both cancers in China.
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              Genomewide association studies and human disease.

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                Author and article information

                Contributors
                Journal
                Cancer Biol Med
                Cancer Biol Med
                CBM
                Cancer Biology & Medicine
                Chinese Anti-Cancer Association (Tianjing China )
                2095-3941
                May 2019
                : 16
                : 2
                : 361-389
                Affiliations
                [1] Department of Cardiothoracic Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China
                Author notes
                Huanwen Chen, E-mail: cyfyyxxwkchw@ 123456126.com

                *These authors contributed equally to this work.

                Article
                cbm-16-2-361
                10.20892/j.issn.2095-3941.2018.0290
                6713634
                31516756
                795804a4-999d-4b16-af4d-6ecde5083f45
                Copyright 2019 Cancer Biology & Medicine

                This work is licensed under a Creative Commons Attribution-NonCommercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

                History
                : 25 August 2018
                : 30 October 2018
                Categories
                Original Article

                gastric cancer,genetic variants,susceptibility,meta-analysis,genome-wide association study

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