Genetic polymorphisms of the E-cadherin promoter and risk of sporadic gastric carcinoma in Chinese populations

作者：Zhang, Baozhen; Pan, Kaifeng; Liu, Zhaojun; Zhou, Jing; Gu, Liankun; Ji, Jiafu; Ma, Junling; You, Wei-cheng; Deng, Dajun^*

来源：Cancer Epidemiology Biomarkers & Prevention, 2008, 17(9): 2402-2408.

DOI：10.1158/1055-9965.EPI-08-0315

• SINGLE NUCLEOTIDE POLYMORPHISM
• INVASION-SUPPRESSOR GENE
• HELICOBACTER-PYLORI
• PROSTATE-CANCER
• STOMACH-CANCER
• BREAST-CANCER
• HIGH-GRADE
• EXPRESSION
• MUTATIONS
• ASSOCIATION

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 -347de/> 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% CD, 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.

• 出版日期2008-9
• 单位北京大学; 北京市肿瘤防治研究所