Genetic Polymorphisms of the E-Cadherin Promoter and Risk of Sporadic Gastric Carcinoma in Chinese Populations

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. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2402–8)

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