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

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 17; no. 9; pp. 2402 - 2408
• Main Authors: Zhang, Baozhen, Pan, Kaifeng, Liu, Zhaojun, Zhou, Jing, Gu, Liankun, Ji, Jiafu, Ma, Junling, You, Wei-cheng, Deng, Dajun
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.09.2008
• Subjects: Asian Continental Ancestry Group - genetics; Biological and medical sciences; Cadherins - genetics; Case-Control Studies; Chi-Square Distribution; China - epidemiology; E-cadherin; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genotype; haplotype; Humans; Incidence; Logistic Models; Male; Medical sciences; Polymerase Chain Reaction; Polymorphism, Genetic; Polymorphism, Restriction Fragment Length; polymorphisms; promoter; Promoter Regions, Genetic - genetics; Risk; sporadic gastric carcinoma; Stomach Neoplasms - epidemiology; Stomach Neoplasms - genetics; Stomach Neoplasms - pathology; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Tumors; Asia; China; Human; Genetic variability; Sporadic; Cell adhesion molecule; Genotype; Risk; Malignant tumor; Stomach cancer; Promoter; Stomach carcinoma; Cancerology; Risk factor; Digestive diseases; E Cadherin; Cancer; Gastric disease; Polymorphism
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-08-0315

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 −347 del >A, −160C>A, −73A>C, +178T>C, and +234 13N ins > del were linked tightly. The −347 del/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 −347 del/del genotype and Helicobacter pylori infection (OR, 4.93; 95% CI, 1.65-14.71). Compared with −347 del -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 −347 del allele of E-cadherin strongly links with the +178T and +234 13N ins alleles. The −347 del/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)