Association Between Tissue Inhibitor of Metalloproteinase-3 Gene Methylation and Gastric Cancer Risk: A Meta-Analysis.
BACKGROUND
The tumor suppressor gene tissue inhibitor of metalloproteinase-3 (TIMP-3) has been reported to be frequently and significantly downregulated in gastric cancer, and its downregulation is correlated with hypermethylation in its promoter region. However, the association between TIMP-3 methylation and gastric cancer risk remains unclear.


OBJECTIVE
In this study, we assessed the relationship between TIMP-3 promoter methylation and gastric cancer risk by performance of a meta-analysis.


METHODS
Relevant studies were identified in a comprehensive literature search using PubMed, Embase, and Web of Science databases. The strength of the association between TIMP-3 methylation and the risk of gastric cancer was assessed by odds ratio (OR) with the corresponding 95% confidence interval (CI). The heterogeneity among studies was tested using the Q-statistics and I(2) metric. The publication bias was examined by Begg's funnel plots and Egger's linear regression test.


RESULTS
A total of 1096 subjects from eight studies were included in the present meta-analysis. Overall, a significant association between TIMP-3 methylation and gastric cancer risk was observed (OR = 8.65; 95% CI 4.31-17.37; p < 0.001). Stratified analyses by ethnicity, sample materials, and detection methods also revealed increased gastric cancer risk in individuals harboring methylated TIMP-3. Moreover, no publication bias was detected in the present meta-analysis.


CONCLUSIONS
Our results show a positive correlation between TIMP-3 promoter methylation and gastric cancer risk and indicated that TIMP-3 promoter methylation may be used as a molecular marker for gastric cancer.
1 Department of Internal Medicine, Binzhou Medical University , Yantai, People's Republic of China .
Jinghua
J
Cao
2 State-Owned Asset Management Department, Binzhou Medical University , Yantai, People's Republic of China .
Zhenfeng
Z
Li
3 Laboratory of Oncology, the Affiliated Hospital of Binzhou Medical University , Binzhou, People's Republic of China .
Lijuan
L
Yang
4 Department of Digestive Medicine, the Affiliated Hospital of Binzhou Medical University , Binzhou, People's Republic of China .
Chengxia
C
Liu
5 Department of Immunology, Binzhou Medical University , Yantai, People's Republic of China .
Xiying
X
Luan
D000328:Adult; D016022:Case-Control Studies; D019175:DNA Methylation; D005006:Ethnicity / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013274:Stomach Neoplasms / Q000208:ethnology / Q000235:genetics*; D019717:Tissue Inhibitor of Metalloproteinase-3 / Q000235:genetics* / Q000378:metabolism
C088390:TIMP3 protein, human; D019717:Tissue Inhibitor of Metalloproteinase-3