title: Selenoprotein S (SEPS1) gene -105G>A promoter polymorphism influences the susceptibility to gastric cancer in the Japanese population.
abstract: BACKGROUND
  Inflammation is a key factor in the process of carcinogenesis from chronic gastritis induced by Helicobacter pylori. Selenoprotein S (SEPS1) is involved in the control of the inflammatory response in the endoplasmic reticulum (ER). Recently the -105G>A polymorphism in the promoter of SEPS1 was shown to increase pro-inflammatory cytokine expression. We examined the association between this polymorphism and the risk of gastric cancer.
  
  
  METHODS
  We took stomach biopsies during endoscopies of 268 Japanese gastric cancer patients (193 males and 75 females, average age 65.3), and 306 control patients (184 males and 122 females, average age 62.7) and extracted the DNA from the biopsy specimens. All subjects provided written informed consent. For the genotyping of the SEPS1 promoter polymorphism at position -105G>A, PCR-RFLP methods were used and the PCR products were digested with PspGI. Logistic-regression analysis was used to estimate odds ratios (OR) and 95% confidence intervals (CI), adjusting for age, sex, and H. pylori infection status.
  
  
  RESULTS
  Among cases, the distribution of genotypes was as follows: 88.4% were GG, 11.2% were GA, and 0.4% were AA. Among controls, the distribution was as follows: 92.5% were GG, 7.2% were GA, and 0.3% were AA. Among males, carrying the A allele was associated with an increased odds of gastric cancer, compared with the GG genotype (OR: 2.0, 95% CI 1.0-4.1, p = 0.07). Compared with the GG genotype, carrying the A allele was significantly associated with increased risks of intestinal type gastric cancer (OR: 2.0, 95%CI 1.0-3.9, p < 0.05) as well as of gastric cancer located in the middle third of the stomach (OR: 2.0, 95%CI 1.0-3.9, p < 0.05).
  
  
  CONCLUSIONS
  The -105G>A promoter polymorphism of SEPS1 was associated with the intestinal type of gastric cancer. This polymorphism may influence the inflammatory conditions of gastric mucosa. Larger population-based studies are needed for clarifying the relation between inflammatory responses and SEPS1 polymorphism.
authors.affiliation: Department of Gastroenterology, Fujita Health University, School of Medicine, Toyoake, Japan. shibat03@fujita-hu.ac.jp
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Shibata
authors.forename: Tomiyasu
authors.initials: T
authors.lastname: Arisawa
authors.forename: Tomomitsu
authors.initials: T
authors.lastname: Tahara
authors.forename: Masaaki
authors.initials: M
authors.lastname: Ohkubo
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshioka
authors.forename: Naoko
authors.initials: N
authors.lastname: Maruyama
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fujita
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kamiya
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Nakamura
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Nagasaka
authors.forename: Masami
authors.initials: M
authors.lastname: Iwata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takahama
authors.forename: Makoto
authors.initials: M
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Hirata
mesh_terms: D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005753:Gastric Mucosa / Q000382:microbiology / Q000473:pathology; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000235:genetics / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D007564:Japan; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D051140:Selenoproteins / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000382:microbiology / Q000473:pathology
chemical_list: D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins