title: Association of single nucleotide polymorphisms in the prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A₂ group IIA (PLA2G2A) genes with susceptibility to esophageal squamous cell carcinoma.
abstract: BACKGROUND
  The prostaglandin-endoperoxide synthase 2 (PTGS2) and phospholipase A2 group IIA (PLA2G2A) genes encode enzymes that are involved in arachidonic acid and prostaglandin biosynthesis. Dysregulation of both genes is associated with inflammation and carcinogenesis, including esophageal squamous cell carcinoma (ESCC). We therefore hypothesized that there is an association between single nucleotide polymorphisms (SNPs) in these genes and susceptibility to ESCC.
  
  
  METHODS
  We performed a gene-wide tag SNP-based association study to examine the association of SNPs in PTGS2 and PLA2G2A with ESCC in 269 patients and 269 healthy controls from Taihangshan Mountain, Henan and Hebei Provinces, the rural area of China which has the highest incidence of esophageal cancer in the world. Thirteen tag SNPs in PLA2G2A and 4 functional SNPs in PTGS2 were selected and genotyped using a high-throughput Mass Array genotyping platform.
  
  
  RESULTS
  We found a modest increased risk of ESCC in subjects with the PTGS2 rs12042763 AA genotype (OR=1.23; 95% CI, 1.00- 3.04) compared with genotype GG. For PLA2G2A, a decreased risk of ESCC was observed in subjects with the rs11677 CT (OR=0.51, 95%CI, 0.29-0.85) or TT genotype (OR=0.51, 95%CI, 0.17-0.96) or the T carriers (CT+TT) (OR=0.52, 95%CI, 0.31-0.85) when compared with the CC genotype. Also for PLA2G2A, rs2236771 C allele carriers were more frequent in the control group (P=0.02). Subjects with the GC (OR=0.55, 95%CI, 0.33-0.93) or CC genotype (OR=0.38, 95% CI, 0.16-0.94) or the C carriers (GC+CC) (OR=0.52, 95%CI, 0.32- 0.85) showed a negative association with ESCC susceptibility.
  
  
  CONCLUSIONS
  Our results suggest that PTGS2 and PLA2G2A gene polymorphisms may modify the risk of ESCC development.
authors.affiliation: Department of Epidemiology and Health Statistics, School of Public Health, Capital Medical University, Beijing, China E-mail : yanhe118@sina.com.
authors.forename: Fen
authors.initials: F
authors.lastname: Liu
authors.forename: Wen-Qiang
authors.initials: WQ
authors.lastname: Wei
authors.forename: Robert T
authors.initials: RT
authors.lastname: Cormier
authors.forename: Shu-Tian
authors.initials: ST
authors.lastname: Zhang
authors.forename: You-Lin
authors.initials: YL
authors.lastname: Qiao
authors.forename: Xin-Qing
authors.initials: XQ
authors.lastname: Li
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Zhu
authors.forename: Yan-Chun
authors.initials: YC
authors.lastname: Zhai
authors.forename: Xiao-Xia
authors.initials: XX
authors.lastname: Peng
authors.forename: Yu-Xiang
authors.initials: YX
authors.lastname: Yan
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Wu
authors.forename: Dian
authors.initials: D
authors.lastname: He
authors.forename: Yan
authors.initials: Y
authors.lastname: He
mesh_terms: D001483:Base Sequence; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D054501:Group II Phospholipases A2 / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D017422:Sequence Analysis, DNA
chemical_list: D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D054501:Group II Phospholipases A2; C516287:PLA2G2A protein, human