Association of CDH1 single nucleotide polymorphisms with susceptibility to esophageal squamous cell carcinomas and gastric cardia carcinomas

Abstract

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.

Association between the CDH1-472delA and -160C>A polymorphisms and diffuse and intestinal gastric cancer in a Mexican population

“…The CDH1 -472delA polymorphism was not associated with either histological type of GC studied; this result was similar to that previously reported in Brazilian (46 cases and 53 controls) (Borges et al, 2010) and Chinese (239 cases and 343 controls) populations (Zhang et al, 2008b).…”

Roles of E-Cadherin (CDH1) Genetic Variations in Cancer Risk: a Meta-analysis

“…For -160 C>A polymorphism, six studies (Wu et al, 2002;Pookot et al, 2006;Grünhage et al, 2007;Pittman et al, 2009;Chien et al, 2011;Corso et al, 2012) were the main origin of heterogeneity, which the heterogeneity was obviously decreased after exclusion of these studies (CA+AA vs. CC: P h =0.056). For +54 C>T polymorphism, the results indicated that Zhang et al (2007) and Jacobs et al (2011) were the main origin of heterogeneity. By removed these two studies, the heterogeneity was decreased (CT+TT vs. CC: P h =0.067).…”

“…For -160 C>A, only 39 studies with available data were enrolled in the pooled analysis, which two papers with two cancer types presented two separate studies individually (Nakamura et al, 2002;Zhang et al, 2007) and a publication with five cancer types provided five independent studies (Cattaneo et al, 2006). Breast cancer (3 studies), gastric cancer (13 studies), colorectal cancer (7 studies), prostate cancer (7 studies) and the others were included in the pooled analysis.…”

“…For CDH1 -347 G>GA polymorphism, seven publications with nine studies were chose for eligibility, which were classified into esophageal cancer (Nakamura et al, 2002;Zhang et al 2007), colorectal cancer (Nakamura et al, 2002;Shin et al 2004) and the others in the Asian and Caucasian population. In addition, the controls of five studies were hospital-based and only four were population-based (Table 1).…”

“…For +54 C>T polymorphism, 9 studies provided casecontrol studies with available data, which consisted of China (7 studies), other countries (2 studies) related to gastric cancer (Al-Moundhri, 2010;Li et al, 2011;Zhang et al, 2007), esophageal cancer (Zhang et al, 2007; and other cancers in the Asian and Caucasian population. Moreover, the controls of all studies were hospital-based (Table 1).…”