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. Material and 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.