title: Genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma in Chinese populations.
abstract: Frequent mutations and loss of expression of E-cadherin have been reported in a number of cancers. E-cadherin germ line mutations lead to a high risk of familial diffused gastric carcinoma. In the present study, to evaluate the effect of genetic polymorphisms in the E-cadherin promoter on the risk of sporadic gastric carcinoma (SGC), a comprehensive study was conducted in two populations with high and low risk of SGC in China, respectively. Five hundred seventy-two SGC cases and 625 controls from low-risk area and 589 individuals enrolled in a long-term follow-up survey in high-risk area were studied. Polymorphisms of E-cadherin around transcription start site (-437 to +314) were analyzed by sequencing. Five variations of -347del>A, -160C>A, -73A>C, +178T>C, and +234 13N ins>del were linked tightly. The -347del/del and its strongly linked +178T/T, +234 13N ins/ins genotypes increased male SGC risk in the high-risk area significantly [odds ratio (OR), 2.22; 95% confidence intervals (95% CI), 1.10-4.46] and correlated with the severity of gastric lesions. A synergetic effect was also observed between -347del/del genotype and Helicobacter pylori infection (OR, 4.93; 95% CI, 1.65-14.71). Compared with -347del-containing haplotypes, the -347A-containing haplotype [A((-347))-C((-160))-A((-73))-C((+178))-13N del((+234))] decreased the risk of SGC among male subjects (OR, 0.61; 95% CI, 0.37-1.01). Such correlation could not be observed among subjects from the low-risk area. The present data suggest that the -347del allele of E-cadherin strongly links with the +178T and +234 13N ins alleles. The -347del/del genotype may increase the susceptibility of SGC among males in the high-risk area of China.
authors.affiliation: Department of Etiology, Peking University School of Oncology, Beijing Cancer Hospital/Institute, Beijing 100036, China.
authors.forename: Baozhen
authors.initials: B
authors.lastname: Zhang
authors.forename: Kaifeng
authors.initials: K
authors.lastname: Pan
authors.forename: Zhaojun
authors.initials: Z
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhou
authors.forename: Liankun
authors.initials: L
authors.lastname: Gu
authors.forename: Jiafu
authors.initials: J
authors.lastname: Ji
authors.forename: Junling
authors.initials: J
authors.lastname: Ma
authors.forename: Wei-cheng
authors.initials: WC
authors.lastname: You
authors.forename: Dajun
authors.initials: D
authors.lastname: Deng