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

Departments of ¹ Etiology, ² Cancer Epidemiology, and ³ Surgery, Peking University School of Oncology, Beijing Cancer Hospital/Institute

Requests for reprints: Dajun Deng, Department of Etiology, Peking University School of Oncology, Beijing Cancer Hospital/Institute, No. 52 Fu-Cheng Road, Beijing 100036, China. Phone: 86-10-8819-6752; Fax: 86-10-8812-2437. E-mail: dengdajun{at}bjmu.edu.cn

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)