Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer

Academic Article


  • Truncating mutations in the gene for the cell to cell adhesion protein E-cadherin are the most consistent genetic alterations observed in sporadic and hereditary diffuse gastric cancer (DGC). In addition to these inactivating mutations, a CDH1 promoter polymorphism at position -160 has been reported to lead to transcriptional downregulation of the gene in vitro. We therefore performed a case-control study to investigate whether this variant is associated with an increased susceptibility to DGC. The frequency of the -160A allele was significantly higher (P<0.005) in 53 diffuse gastric cancer cases compared to 70 matched controls. The odds ratio associated with the A-allele was 2.27 for CA-heterozygotes (95%CI 1.16-4.44) and 7.84 for AA-homozygotes (95%CI 2.89-21.24). Two additional polymorphisms (the 48+6T→C and the 2076C→T variant) were genotyped and shown to be equally distributed among cases and controls. Haplotype analysis with the three polymorphisms confirmed an association with disease (P<0.004). However, this analysis suggested the -160C→A CDH1 promoter polymorphism may be in linkage disequilibrium with a distinct aetiological locus or acts in combination with other functional variants in or near the CDH1 region.
  • Authors

    Published In

  • Oncogene  Journal
  • Digital Object Identifier (doi)

    Author List

  • Humar B; Graziano F; Cascinu S; Catalano V; Ruzzo AM; Magnani M; Toro T; Burchill T; Futschik ME; Merriman T
  • Start Page

  • 8192
  • End Page

  • 8195
  • Volume

  • 21
  • Issue

  • 53