Roles of E-cadherin (CDH1) genetic variations in cancer risk: a meta-analysis.

Qi-Wen Deng,Shu-Kui Wang,Hui-Ling Sun,Yu-Qin Pan,Ye-Qiong Xu,Tian-Yi Gao,Bang-Shun He,Rui Li,Guo-Qi Song

doi:10.7314/apjcp.2014.15.8.3705

Abstract

E-Cadherin (CDH1) genetic variations may be involved in invasion and metastasis of various cancers by altering gene transcriptional activity of epithelial cells. However, published studies on the association of CDH1 gene polymorphisms and cancer risk remain contradictory, owing to differences in living habits and genetic backgrounds. To derive a more better and comprehensive conclusion, the present meta-analysis was performed including 57 eligible studies of the association between polymorphisms of CDH1 gene promoter -160 C>A, -347 G>GA and 3'-UTR +54 C>T and cancer risk. Results showed that these three polymorphisms of CDH1 were significantly associated with cancer risk. For -160 C>A polymorphism, -160A allele carriers (CA and CA+AA) had an increased risk of cancer compared with the homozygotes (CC), and the similar result was discovered for the -160A allele in the overall analyses. In the subgroup analyses, obvious elevated risk was found with -160A allele carriers (AA, CA, CA+AA and A allele) for prostate cancer, while a decreased colorectal cancer risk was shown with the AA genotype. For the -347 G>GA polymorphism, the GAGA genotype was associated with increased cancer risk in the overall analysis with homozygous and recessive models. In addition, results of subgroup analysis indicated that the elevated risks were observed in colorectal cancer and Asian descendants. For +54 C>T polymorphism, a decreased risk of cancer was found in heterozygous, dominant and allele models. Moreover, +54T allele carriers (CT, CT+TT genotype and T allele) showed a potential protective factor in gastric cancer and Asian descendants.

Highlights

Cancer is one of serious diseases threatening public health, and is becoming more prevalent worldwide, due to the aging and growth of the population
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 a stratified analysis by cancer type, a statistically significant association was observed for prostate cancer, but we found that there was a significant decreased risk between –C160A polymorphism and colorectal cancer risk

Summary

Introduction

Cancer is one of serious diseases threatening public health, and is becoming more prevalent worldwide, due to the aging and growth of the population. Evidence from epidemiological and genetic studies provides more focus on the inherited susceptibility to cancer. Among these genetic factors, the E-cadherin (CDH1) gene, consists of a large extracellular domain composed of smaller transmembrane and cytoplasmic domains and five repeat domains (Ringwald et al, 1987). Abnormal expression of CDH1 is often occurred in a number of human epithelial cancers (Ghadimi et al, 1999). The emerging numbers of studies showed that three genetic variations within E-Cadherin gene have been proven to be involved in oncogenesis and development (Li et al, 2000; Shin et al, 2004; Li et al, 2011)

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Conclusion