Helicobacter pylori infection in relation to E-cadherin gene promoter polymorphism and hypermethylation in sporadic gastric carcinomas.
OBJECTIVE
To study Helicobacter pylori (H. pylori) infection in relation to E-cadherin (E-cad) promoter polymorphism and hypermethylation in GCs.


METHODS
Specimens were taken from representative cancerous lesions and adjacent non-cancerous epithelia of 67 resected GCs. H. pylori was detected by real-time PCR of the cagA gene from non-neoplastic epithelium. E-cad promoter polymorphism and hypermethylation were determined by restriction fragment length polymorphism analysis and methylation-specific PCR, respectively. Expression of E-cad protein was determined by immunohistochemistry.


RESULTS
H. pylori was found in 57% of patients with GC. H. pylori infection was more frequently found in tumors with the -160C/C genotype than those with the -160C/A and -160A/A genotypes (74% vs 47%, P = 0.02). H. pylori infection was associated with E-cad methylation in non-neoplastic epithelium; however, no significant difference in H. pylori was observed between methylated and unmethylated cancerous lesions.


CONCLUSIONS
Patients with the -160C/C genotype might require H. pylori infection to promote the inactivation of CDH1, suggesting that H. pylori infection might affect GC in an initial stage because polymorphism is germ line. Mechanism of hypermethylation of CDH1 promoter in GC is complex, and H. pylori infection might affect it in an initial stage.
Liu
Yao-Chi
YC
Division of General Surgery, Tri-Service General Hospital, No. 325, Sec. 2, Cheng-Kung Road, Neihu 114, Taipei, Taiwan, China. dlyaochi@yahoo.com.tw
Shen
Chen-Yang
CY
Wu
Hurng-Sheng
HS
Chan
De-Chuan
DC
Chen
Cheng-Jueng
CJ
Yu
Jyh-Cherng
JC
Yu
Cheng-Ping
CP
Harn
Horng-Jyh
HJ
Shyu
Rong-Yaun
RY
Shih
Yu-Lueng
YL
Hsieh
Chung-Bao
CB
Hsu
Huan-Mieng
HM
D015820:Cadherins / Q000235:genetics*; D002277:Carcinoma / Q000150:complications*; D019175:DNA Methylation; D016481:Helicobacter Infections / Q000150:complications*; D016480:Helicobacter pylori; D006801:Humans; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000150:complications*
D015820:Cadherins