title: A novel diffuse gastric cancer susceptibility variant in E-cadherin (CDH1) intron 2: a case control study in an Italian population.
abstract: BACKGROUND
  Inherited genetic factors such as E-cadherin (CDH1) promoter variants are believed to influence the risk towards sporadic diffuse gastric cancer (DGC). Recently, a new regulatory region essential for CDH1 transcription has been identified in CDH1 intron 2.
  
  
  METHODS
  We genotyped all known polymorphisms located within conserved sequences of CDH1 intron 2 (rs10673765, rs9932686, rs1125557, rs9282650, rs9931853) in an Italian population consisting of 134 DGC cases and 100 healthy controls (55 patient relatives and 45 unrelated, matched individuals). The influence of individual variants on DGC risk was assessed using chi2-tests and logistic regression. The relative contribution of alleles was estimated by haplotype analysis.
  
  
  RESULTS
  We observed a significant (p < 0.0004) association of the CDH1 163+37235G>A variant (rs1125557) with DGC risk. Odds ratios were 4.55 (95%CI = 2.09-9.93) and 1.38 (95%CI = 0.75-2.55) for AA and GA carriers, respectively. When adjusted for age, sex, smoking status, alcohol intake and H. pylori infection, the risk estimates remained largely significant for AA carriers. Haplotype analysis suggested the 163+37235A-allele contributes to disease risk independently of the other variants studied.
  
  
  CONCLUSIONS
  The CDH1 163+37235G>A polymorphism may represent a novel susceptibility variant for sporadic DGC if confirmed in other populations. Considering the broad expression of E-cadherin in epithelia, this exploratory study encourages further evaluation of the 163+37235A-allele as a susceptibility variant in other carcinomas.
authors.affiliation: Cancer Genetics Laboratory, Department of Biochemistry, University of Otago, Dunedin 9054, Aotearoa New Zealand. nasso300@student.otago.ac.nz
authors.forename: Soroush
authors.initials: S
authors.lastname: Nasri
authors.forename: Helen
authors.initials: H
authors.lastname: More
authors.forename: Francesco
authors.initials: F
authors.lastname: Graziano
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ruzzo
authors.forename: Emily
authors.initials: E
authors.lastname: Wilson
authors.forename: Anita
authors.initials: A
authors.lastname: Dunbier
authors.forename: Cushla
authors.initials: C
authors.lastname: McKinney
authors.forename: Tony
authors.initials: T
authors.lastname: Merriman
authors.forename: Parry
authors.initials: P
authors.lastname: Guilford
authors.forename: Mauro
authors.initials: M
authors.lastname: Magnani
authors.forename: Bostjan
authors.initials: B
authors.lastname: Humar
mesh_terms: D000328:Adult; D000368:Aged; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D007558:Italy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D050436:Regulatory Elements, Transcriptional / Q000235:genetics; D013274:Stomach Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: D015820:Cadherins