Zhang X-F, Wang Y-M, Ge H, Cao Y-Y, Chen Z-F, Wen D-G, Guo W, Wang N, Li Y, Zhang J-H
Hebei Cancer Institute and the Fourth Affiliated Hospital, Hebei Medical University, Shijiazhuang Hebei Province, China.
Dis Esophagus. 2008;21(1):21-9. doi: 10.1111/j.1442-2050.2007.00724.x.
E-cadherin (CDH1) is a tumor suppressor involved in epithelial cell-cell interactions. Single nucleotide polymorphisms (SNP) in the CDH1 gene, -160C/A and -347G/GA in the 5'-promoter region and +54C/T in the 3'-untranslated region (UTR) have been shown to be associated with tumor development and progression via modifying transcriptional activity, mRNA stability or protein expression. To investigate the influence of CDH1 SNP on susceptibility to esophageal squamous cell carcinomas (ESCC) and gastric cardia adenocarcinomas (GCA), a case-control study was conducted among 333 ESCC patients, 239 GCA patients and 343 controls from a northern Chinese population. CDH1 polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis. The results showed that; (i) genotypes with the +54C allele (C/C or C/T) significantly increased the risk of developing both ESCC and GCA compared to the +54T/T genotype (age and gender adjusted odds ratio [OR] = 1.45 and 2.28, 95% confidence interval [CI] = 1.06-1.99 and 1.58-3.30, respectively), and this association was significant only among non-smokers (OR = 1.68 and 2.64, 95% CI = 1.01-2.80 and 1.43-4.87 for ESCC and GCA, respectively), and individuals without a family history of upper gastrointestinal cancer (OR = 2.63 and 2.97, 95% CI = 1.36-5.10 and 95% CI = 1.32-6.68 for ESCC and GCA, respectively); (ii) compared with the -347G/G genotype, the -347GA and GA/GA genotypes significantly increased the risk of developing GCA (OR = 1.45, 95 % CI = 1.03-2.04); (iii) there was a significant association of CDH1-160C/-347G/+54C and -160C/-347GA/+54C haplotypes with the development of GCA, compared with the -160C/-347G/+54T haplotype (OR = 1.80 and 2.21, 95% CI = 1.33-2.44 and 1.43-3.42, respectively); and (iv) the influence of CDH1 SNP on the depth of tumor invasion and lymphatic metastasis in ESCC and GCA patients was not observed in this study. The present study indicates that CDH1 polymorphisms might modify susceptibility to ESCC and/or GCA.
E-钙黏蛋白（CDH1）是一种参与上皮细胞间相互作用的肿瘤抑制因子。CDH1基因5'-启动子区域的单核苷酸多态性（SNP），即-160C/A和-347G/GA，以及3'-非翻译区（UTR）的+54C/T，已被证明可通过改变转录活性、mRNA稳定性或蛋白质表达与肿瘤的发生发展相关。为了研究CDH1 SNP对食管鳞状细胞癌（ESCC）和胃贲门腺癌（GCA）易感性的影响，在中国北方人群的333例ESCC患者、239例GCA患者和343例对照中进行了一项病例对照研究。通过聚合酶链反应-限制性片段长度多态性分析对CDH1多态性进行基因分型。结果显示：（i）与+54T/T基因型相比，携带+54C等位基因（C/C或C/T）的基因型显著增加了患ESCC和GCA的风险（年龄和性别校正优势比[OR]=1.45和2.28，95%置信区间[CI]=1.06-1.99和1.58-3.30），且这种关联仅在非吸烟者中显著（ESCC和GCA的OR分别为1.68和2.64，95%CI分别为1.01-2.80和1.43-4.87），以及在上消化道癌症无家族史的个体中显著（ESCC和GCA的OR分别为2.63和2.97，95%CI分别为1.36-5.10和1.32-6.68）；（ii）与-347G/G基因型相比，-347GA和GA/GA基因型显著增加了患GCA的风险（OR = 1.45，95%CI = 1.03-2.04）；（iii）与-160C/-347G/+54T单倍型相比，CDH1 -160C/-347G/+54C和-160C/-347GA/+54C单倍型与GCA的发生显著相关（OR分别为1.80和2.21，95%CI分别为1.33-2.44和1.43-3.42）；（iv）本研究未观察到CDH1 SNP对ESCC和GCA患者肿瘤浸润深度和淋巴转移的影响。本研究表明，CDH1多态性可能会改变对ESCC和/或GCA的易感性。
