Association between CDH1 haplotypes and gastric cancer risk in a Japanese population.
OBJECTIVE
A c. -285C >A single nucleotide polymorphism (SNP) in the promoter region of the E-cadherin (CDH1) gene, which is a tumor suppressor in gastric cancer (GC), has been shown to decrease gene transcription, but GC case-control studies of this SNP have yielded controversial results. A haplotype study in an Italian population showed that haplotypes based on three SNPs, including the c. -285C >A, are associated with susceptibility to GC. Hence, the purpose of the present study was to carry out a more comprehensive genetic analysis of CDH1 using haplotype-tagging SNPs (htSNPs) in a Japanese case-control study to identify the CDH1 haplotype associated with susceptibility to GC in a Japanese population.


METHODS
First, 11 SNPs in the CDH1 gene were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis in 30 healthy individuals. Haplotype frequencies were estimated with the expectation-maximization algorithm, and 7 common haplotypes of the CDH1 gene whose frequency was at least 3.3% were identified. Next, 5 htSNPs (c. -285C >A, c.48+6T >C, c.164 -3159T >C, c.2076C >T, and c.2296 -616G >C) were genotyped in a hospital-based case-control study of 148 GC patients and 292 age- and gender-matched healthy controls, and haplotype frequencies based on the 5 htSNPs were estimated.


RESULTS
Although none of the 5 htSNPs was related to an overall risk of GC, frequencies of the ATCTG and CTTTG haplotypes were significantly higher and lower, respectively, in the GC cases than in the controls (p<0.05).


CONCLUSIONS
These results suggest that the ATCTG and CTTTG CDH1 haplotypes may be associated with an increased risk and decreased risk, respectively, of GC in the Japanese population.
Yamada
Hidetaka
H
First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Shinmura
Kazuya
K
Ikeda
Shinobu
S
Tao
Hong
H
Otani
Tetsuya
T
Hanaoka
Tomoyuki
T
Tsuneyoshi
Toshihiro
T
Tsugane
Shoichiro
S
Sugimura
Haruhiko
H
D000328:Adult; D000368:Aged; D000465:Algorithms; D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007564:Japan / Q000453:epidemiology; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012306:Risk; D013274:Stomach Neoplasms / Q000235:genetics*
D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins