title: Genetic polymorphism at codon 546 of the human RAD17 contributes to the risk for esophageal squamous cell carcinoma.
abstract: Human RAD17, a human homolog of the Schizosaccharomyces pombe cell cycle checkpoint gene RAD17, plays a significant role in activating checkpoint signals in response to DNA damage. We evaluated the association of hRAD17 Leu546Arg (rs1045051), a missense single nucleotide polymorphism, with the risk of esophageal squamous cell carcinoma in relation to smoking and alcohol consumption history in 154 esophageal squamous cell carcinoma male patients and 695 cancer-free male controls by a case-control study conducted in Japan. The results showed that the hRAD17 Arg/Arg genotype compared to the Leu/Leu and Leu/Arg genotypes was significantly associated with the risk of the esophageal squamous cell carcinoma with an adjusted odds ratios of 2.22 (95% CI: 1.19-4.16 P=0.013). In stratified studies, the risk of esophageal squamous cell carcinoma was markedly higher in light drinkers (less than 23 g ethanol/day) with the Arg/Arg genotype than in heavy drinkers (excess of 23 g ethanol/day) with the Arg/Arg genotype (OR=2.83, 95% CI: 1.05-7.61, P=0.04). We concluded that the genetic variant of hRAD17 Leu546Arg polymorphism exerts a significant effect on esophageal squamous cell carcinoma risk among Japanese men.
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Yasuda
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Sakai
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Sachio
authors.initials: S
authors.lastname: Ito
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Mita
authors.affiliation: Department of Gastroenterology and Hepatology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Sonoyama
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Tanabe
authors.affiliation: Department of Gastroenterological Surgery, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shirakawa
authors.affiliation: Department of General Surgery, Kawasaki Medical School Kawasaki Hospital Okayama 700-8505, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Naomoto
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Katayama
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Okayama 700-8558, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Shimizu
keywords: DNA damage; Esophageal squamous cell carcinoma; human RAD17; single nucleotide polymorphism