Contribution of the -160C/A polymorphism in the E-cadherin promoter to cancer risk: a meta-analysis of 47 case-control studies.
BACKGROUND
The -160C/A polymorphism (rs16260) of E-cadherin, a tumor repressor gene, has been shown to be a tumor susceptibility allele for various types of cancers. Because the significance of this polymorphism to cancer risk has been recognized, there are increasing studies investigating -160C/A in different types of cancers and ethnic populations. However, there is still uncertainty about the level of risk for a variety of cancers.


METHODS
To resolve the controversial question raised by these studies as of March 2012 and provide more statistical power for detecting the significance of -160C/A, we performed a meta-analysis of 47 case-control studies in 16 types of cancers (18,194 cases and 20,207 controls). A meta-regression model and subgroup analysis were employed to identify the source of heterogeneity. Publication bias was evaluated, and sensitivity analysis and cumulative evidence assessment were also performed.


RESULTS
Using fixed- and random-effects models, the -160AA homozygote was more susceptible to urothelial cancer compared with the -160CA heterozygote. Additionally, the -160A allele is an ethnicity-dependent risk factor for prostate and colorectal cancers. Carriers of the -160A allele in Asians and Europeans were more susceptible to prostate cancer, whereas their North American counterparts seemed tolerant. The -160AA homozygote plays a protective role for Europeans who develop colorectal cancer. The stability of these observations was confirmed by a one-way sensitivity analysis. However, the cumulative evidence for all cancer types was considered 'weak' using the Venice guidelines.


CONCLUSIONS
A meta-analysis indicated that the -160A allele of E-cadherin provides a higher risk for the development of prostate and urothelial cancers and a protective role for colorectal cancer in an ethnicity-dependent manner.
Endocrinology Department, Shanghai East Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Science and Technology, Tongji University, Shanghai, People's Republic of China.
Lin
L
Wang
Guiying
G
Wang
Chenqi
C
Lu
Bo
B
Feng
Jiuhong
J
Kang
D000483:Alleles; D015820:Cadherins / Q000235:genetics*; D016022:Case-Control Studies; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
D015820:Cadherins