title: Association of EPAS1 gene rs4953354 polymorphism with susceptibility to lung adenocarcinoma in female Japanese non-smokers.
abstract: BACKGROUND
  Hypoxia-inducible factor-2α (also called endothelial periodic acid-Schiff domain protein 1 [EPAS1]) seems to play an important role in some carcinogenesis, though there is no information on the relationship between single nucleotide polymorphism of EPAS1 and lung cancer development. The aim of this study was to explore a possible association of the EPAS1 gene rs4953354 polymorphism with susceptibility to lung cancer.
  
  
  METHODS
  A case-control study of 346 patients with non-small-cell lung carcinoma (adenocarcinoma = 249, squamous cell carcinoma = 97) and 247 healthy control subjects was carried out. A/G polymorphism within an intron 2 of the EPAS1 (rs4953354) was determined by direct sequencing.
  
  
  RESULTS
  A frequency of lung adenocarcinoma patients with a minor allele G (A/G or G/G genotype) at the rs4953354 was much higher than that of controls (odds ratio, 1.800; 95% confidence interval, 1.161-2.791; p = 0.008). This association was more evident when analyzed using female never-smokers (odds ratio, 3.31; 95% confidence interval, 1.21-9.01; p = 0.017). Mutations in epidermal growth factor receptor tended to be frequent in patients with G allele at the rs4953354, compared with those with other genotypes.
  
  
  CONCLUSIONS
  The EPAS1 rs4953354 may be a potentially susceptible marker for development of lung adenocarcinoma, especially in female never-smokers.
authors.affiliation: *Division of Medical Oncology & Respiratory Medicine, Department of Internal Medicine, Shimane University Faculty of Medicine, Shimane, Japan; †Research Institute for Radiation Biology and Medicine, Department of Radiation Medicine, Hiroshima University, Hiroshima, Japan; ‡Natural Science Center for Basic Research and Development, Hiroshima University, Hiroshima, Japan; §Higashihiroshima Medical Center, Department of Respiratory Medicine, Hiroshima, Japan; and ‖Division of Translational Research, Research Center for Genomic Medicine, Saitama Medical University, Saitama, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Iwamoto
authors.forename: Keiji
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Yumi
authors.initials: Y
authors.lastname: Nishio
authors.forename: Andika Chandra
authors.initials: AC
authors.lastname: Putra
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fuchita
authors.forename: Miki
authors.initials: M
authors.lastname: Ohe
authors.forename: Akihisa
authors.initials: A
authors.lastname: Sutani
authors.forename: Takashige
authors.initials: T
authors.lastname: Kuraki
authors.forename: Keiko
authors.initials: K
authors.lastname: Hiyama
authors.forename: Isao
authors.initials: I
authors.lastname: Murakami
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Eguchi
authors.forename: Takeshi
authors.initials: T
authors.lastname: Isobe
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000077192:Adenocarcinoma of Lung; D044466:Asian People / Q000235:genetics*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D000099162:Endothelial PAS Domain-Containing Protein 1