title: Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer: Meta-analysis using Mendelian randomization.
abstract: OBJECTIVE
  To undertake a systematic meta-analysis of all variants in the gene encoding receptor for advanced glycation end products (RAGE) to summarize their associations with cancer risk and changes in the levels of circulating soluble RAGE (sRAGE), with the aim of determining possible causality between circulating sRAGE and cancer risk.
  
  
  METHODS
  Articles written in English were retrieved from MEDLINE® and EMBASE® databases. Two researchers independently identified eligible articles and extracted the data (analysed using STATA® software version 12.0).
  
  
  RESULTS
  Fifteen articles qualified for inclusion in the meta-analysis of the RAGE-cancer association and three examined the RAGE-sRAGE relationship. The 82Ser/82Ser genotype was significantly associated with overall cancer risk compared with the 82Gly/Gly genotype (odds ratio 1.75, 95% confidence interval [CI] 1.46, 2.10). Carriers of the 82Ser/82Ser genotype had significantly reduced circulating sRAGE concentrations compared with the 82Gly/82Gly genotype. Mendelian randomization analysis demonstrated that a reduction of 100, 200 and 300 pg/ml in circulating sRAGE concentrations was associated with a 1.11-fold (95% CI 1.06, 1.25), 1.24-fold (95% CI 1.11, 1.57) and 1.38-fold (95% CI 1.18, 1.96) increased risk of developing cancer, respectively.
  
  
  CONCLUSIONS
  Genetically lowered concentrations of circulating sRAGE might cause an increased risk of cancer.
authors: Department of Gastroenterology, Yantai Yuhuangding Hospital, Yantai, Shandong Province, China.
authors: Qingxian
authors: Q
authors: Huang
authors: Medicine and Pharmacy Research Centre, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Jia
authors: J
authors: Mi
authors: Imaging Centre, The Affiliated Hospital of Weifang Medical University, Weifang, Shandong Province, China.
authors: Xizhen
authors: X
authors: Wang
authors: Medicine and Pharmacy Research Centre, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Fang
authors: F
authors: Liu
authors: Medicine and Pharmacy Research Centre, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Dan
authors: D
authors: Wang
authors: Medicine and Pharmacy Research Centre, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Dong
authors: D
authors: Yan
authors: Institute of Molecular Imaging, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Bin
authors: B
authors: Wang
authors: Institute of Pharmacology, Binzhou Medical University, Yantai, Shandong Province, China.
authors: Shuping
authors: S
authors: Zhang
authors: Medicine and Pharmacy Research Centre, Binzhou Medical University, Yantai, Shandong Province, China tiangengshandong@yeah.net.
authors: Geng
authors: G
authors: Tian
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics*; D005260:Female; D015870:Gene Expression; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D057182:Mendelian Randomization Analysis; D009369:Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood / Q000235:genetics*; D012306:Risk
chemical_list: C000593871:AGER protein, human; D014408:Biomarkers, Tumor; D000067759:Receptor for Advanced Glycation End Products
keywords: Mendelian randomization; Receptor for advanced glycation end products (RAGE); cancer; meta-analysis