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.
Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer / B., Humar; F., Graziano; Cascinu, Stefano; V., Catalano; A. M., Ruzzo; M., Magnani; T., Toro; T., Burchill; M. E., Futschik; T., Merriman; P., Guilford. - In: ONCOGENE. - ISSN 0950-9232. - 21:(2002), pp. 8192-8195. [10.1038/sj.onc.1205921]
Association of CDH1 haplotypes with susceptibility to sporadic diffuse gastric cancer.
CASCINU, Stefano;
2002-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.