Yamada Hidetaka, Shinmura Kazuya, Ikeda Shinobu, Tao Hong, Otani Tetsuya, Hanaoka Tomoyuki, Tsuneyoshi Toshihiro, Tsugane Shoichiro, Sugimura Haruhiko
First Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.
Scand J Gastroenterol. 2007 Dec;42(12):1479-85. doi: 10.1080/00365520701478436.
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.
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.
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).
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.
E-钙黏蛋白（CDH1）基因启动子区域的一个c.-285C＞A单核苷酸多态性（SNP），该基因在胃癌（GC）中是一种肿瘤抑制基因，已被证明会降低基因转录，但关于该SNP的GC病例对照研究结果存在争议。一项针对意大利人群的单倍型研究表明，基于包括c.-285C＞A在内的三个SNP的单倍型与GC易感性相关。因此，本研究的目的是在一项日本病例对照研究中，使用单倍型标签SNP（htSNP）对CDH1进行更全面的基因分析，以确定与日本人群GC易感性相关的CDH1单倍型。
首先，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）分析对30名健康个体的CDH1基因中的11个SNP进行基因分型。采用期望最大化算法估计单倍型频率，确定了CDH1基因7种常见单倍型，其频率至少为3.3%。接下来，在一项基于医院的病例对照研究中，对148例GC患者和292名年龄及性别匹配的健康对照进行了5个htSNP（c.-285C＞A、c.48+6T＞C、c.164-3159T＞C、c.2076C＞T和c.2296-616G＞C）的基因分型，并估计了基于这5个htSNP的单倍型频率。
虽然这5个htSNP均与GC的总体风险无关，但在GC病例中，ATCTG和CTTTG单倍型的频率分别显著高于和低于对照组（p＜0.05）。
这些结果表明，在日本人群中，ATCTG和CTTTG CDH1单倍型可能分别与GC风险增加和降低有关。
