title: An Updated and Comprehensive Meta-Analysis of Association Between Seven Hot Loci Polymorphisms from Eight GWAS and Glioma Risk.
abstract: Eight genome-wide association studies (GWASs) found that seven loci (rs2736100, rs4295627, rs4977756, rs498872, rs11979158, rs2252586, rs6010620) polymorphisms could elevate the risk of glioma, one of the most common types of primary brain cancer in adults. However, the replication studies about these seven loci obtained inconsistent results. In order to derive a more accurate estimation about the relationship between the selected single-nucleotide polymorphism (SNP) and susceptibility to glioma, we conducted a meta-analysis containing all eligible published case control studies to evaluate the association. An overall literature search was conducted using the database of PubMed, Science Direct, China national knowledge infrastructure (CNKI), and Embase. Seventeen articles with 25 studies were included in the meta-analysis. Glioma risk (odds ratio, OR; 95 % confidential interval, 95 %CI) was estimated with the random-effect model or the fixed-effects model. STATA 12.0 was applied to analyze all statistical data. Results showed that seven hot loci were all associated with increased risk of glioma (rs2736100, OR = 1.28, 95 %CI = 1.23-1.32; rs4295627, OR = 1.34, 95 %CI = 1.21-1.47; rs4977756, OR = 1.24, 95 %CI = 1.20-1.28; rs498872, OR = 1.24, 95 %CI = 1.15-1.33; rs6010620, OR = 1.29, 95 %CI = 1.24-1.35; rs11979158: OR = 1.18, 95 %CI = 1.10-1.25; rs2252586: OR = 1.18, 95 %CI = 1.10-1.25). Additionally, subgroup analysis by stages of glioma found that variation of rs11979158 had stronger relationship with high-grade (OR = 1.32, 95 %CI = 1.19-1.45) than low-grade glioma (OR = 1.12, 95 % CI = 1.03-1.21). Similarly, stratified analysis of rs2252586 by stages revealed the similar trend, with OR of 1.26 (95 %CI = 1.17-1.35) in high-grade glioma and OR of 1.15 (95 %CI = 1.08-1.22) in low-grade glioma. In summary, the present study showed that mutations of the seven loci could elevate the risk of glioma significantly. However, more other factors that could be related with glioma should be considered in further studies.
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Fifth People's Hospital, Fudan University, Minhang District, No. 801 Heqing Road, Shanghai, 200240, China. bbmcwq@163.com.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Division of Human Genetics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, 45229, USA.
authors.forename: Xiaotao
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000483:Alleles; D001932:Brain Neoplasms / Q000235:genetics*; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005910:Glioma / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D011110:Polymorphism, Genetic; D017594:Publication Bias; D012307:Risk Factors
keywords: CCDC26; CDKN2A/B; EGFR; GWAS; Glioma; Meta-analysis; PHLDB1; RTEL1; Single-nucleotide polymorphism; TERT