title: CDH1 polymorphisms and haplotypes in sporadic diffuse and intestinal gastric cancer: a case-control study based on direct sequencing analysis.
abstract: BACKGROUND
  Findings related to the influence of the -160C → A promoter polymorphism and haplotypes of the E-cadherin (CDH1) gene have not been consistent in previous studies regarding the risk for sporadic gastric cancer. Investigators in most previous studies detected those genotypes using restriction fragment length polymorphism analysis. Therefore, we conducted a case-control study to investigate the association of the CDH1 - 160C → A promoter polymorphism and haplotypes for cancer risk related to sporadic diffuse and intestinal gastric cancer by direct sequencing analysis.
  
  
  METHODS
  We included 107 diffuse gastric cancer cases, 60 intestinal gastric cancer cases and 134 controls. The genotypic polymorphisms in the -160 promoter region, exons and intron-exon boundaries of CDH1 were detected by direct sequencing analysis. Genotype frequencies were compared. The CDH1 - 160C → A promoter polymorphism and four polymorphisms (48 + 6 T → C, 2076C → T, 2253C → T and 1937-13 T → C) were included in the haplotype analyses, which were estimated using the expectation-maximization algorithm.
  
  
  RESULTS
  Compared to controls, the frequency of the -160A allele was significantly higher in diffuse gastric cancer cases (P = 0.005), but it was not significantly different in intestinal gastric cancer cases (P = 0.119). Two sets of three-marker haplotypes (-160C → A, 48 + 6 T → C, 2076C → T and -160C → A, 1937-13 T → C, 2253C → T) were associated with the risk of diffuse gastric cancer (P = 0.011 and P = 0.042, respectively).
  
  
  CONCLUSIONS
  Based on direct sequencing analysis, our findings suggest that the CDH1 - 160C → A promoter polymorphism and haplotypes play significant roles in cancer risk for sporadic diffuse gastric cancer, but not for intestinal gastric cancer, in a Taiwanese population.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Chu
authors.forename: Cheng-Jueng
authors.initials: CJ
authors.lastname: Chen
authors.forename: De-Chuan
authors.initials: DC
authors.lastname: Chan
authors.forename: Hurng-Sheng
authors.initials: HS
authors.lastname: Wu
authors.affiliation: Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, No, 325, Sec, 2, Cheng-Kung Road, Neihu, Taipei 11490, Taiwan. dlyaochi@gmail.com.
authors.forename: Yao-Chi
authors.initials: YC
authors.lastname: Liu
authors.forename: Chen-Yang
authors.initials: CY
authors.lastname: Shen
authors.forename: Tzu-Ming
authors.initials: TM
authors.lastname: Chang
authors.forename: Jyh-Cherng
authors.initials: JC
authors.lastname: Yu
authors.forename: Horng-Jyh
authors.initials: HJ
authors.lastname: Harn
authors.forename: Cheng-Ping
authors.initials: CP
authors.lastname: Yu
authors.forename: Ming-Hsin
authors.initials: MH
authors.lastname: Yang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics*; D015820:Cadherins / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007124:Immunoenzyme Techniques; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics; D017422:Sequence Analysis, DNA; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins