American Journal of Epidemiology Advance Access originally published online on October 29, 2007
American Journal of Epidemiology 2008 167(1):7-14; doi:10.1093/aje/kwm264
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The E-cadherin Gene Polymorphism –160C
A and Cancer Risk: A HuGE Review and Meta-Analysis of 26 Case-Control Studies
1 Laboratory of Population and Quantitative Genetics, Institute of Genetics and Biostatistics, School of Life Sciences, Fudan University, Shanghai, People's Republic of China
2 School of Biosciences, University of Birmingham, Edgbaston, Birmingham, United Kingdom
Correspondence to Professor Z. W. Luo, School of Biosciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, United Kingdom (e-mail: z.luo{at}bham.ac.uk or zwluo{at}fudan.edu.cn).
Received for publication April 9, 2007. Accepted for publication August 13, 2007.
A single nucleotide polymorphism, –160C
A, has been identified in the promoter region of the E-cadherin gene and has been shown to alter its transcriptional activity. To assess susceptibility of –160A allele carriers to seven types of cancers, the authors conducted a comprehensive meta-analysis, up to November 2006, of 26 case-control studies comprising 7,042 cases and 7,011 controls. Pooled odds ratios and 95% confidence intervals were calculated by using the random-effects model. Publication bias, subgroup, and sensitivity analyses were also performed, which showed that –160A allele carriers, compared with noncarriers, had about a 17–19% increased risk of several invasive/metastatic tumors. Analyses of various types of cancers revealed that, in Europeans, the –160AA homozygote was associated with an increased risk of urothelial cancer, carriers of –160A were at increased risk of lung and prostate cancers, and carriers of –160A with gastric cancer were found to suffer a significantly increased risk, whereas their Asian counterparts seemed to be tolerant. No evidence was found that the –160A allele predisposed its carriers to breast, colorectal, or esophageal cancers. These findings indicate that –160A of the E-cadherin gene is emerging as a low-penetrance tumor susceptibility allele for the development of gastric, lung, prostate, and urothelial cancers.
E-cadherin; epidemiology; meta-analysis; mutation; neoplasms
Abbreviations: CI, confidence interval; OR, odds ratio
Editor's note: This article also appears on the website of the Human Genome Epidemiology Network (http://www.cdc.gov/genomics/hugenet/default.htm).
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