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Open Access Highly Accessed Research article

Association between RUNX3 promoter methylation and gastric cancer: a meta-analysis

Xiao-yuan Fan1, Xin-lei Hu2, Tie-mei Han1, Na-na Wang1, Yi-miao Zhu1, Wen Hu1, Zhen-hua Ma1, Chen-jing Zhang1, Xiang Xu3, Zai-yuan Ye4, Chun-mao Han5 and Wen-sheng Pan1*

Author Affiliations

1 Department of Gastroenterology, Second Affiliated Hospital, Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, China

2 Department of Orthopaedics, Second Affiliated Hospital (Binjiang Branch), Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, China

3 Department of Pharmacy, Second Affiliated Hospital, Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, China

4 Department of General Surgery, Zhejiang Provincial People's Hospital, 158 Shangtang Road, Hangzhou, China

5 Department of Burns, Second Affiliated Hospital, Zhejiang University, School of Medicine, 88 Jiefang Road, Hangzhou, China

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BMC Gastroenterology 2011, 11:92  doi:10.1186/1471-230X-11-92

Published: 25 August 2011

Abstract

Background

Runt-related transcription factor 3 (RUNX3) is a member of the runt-domain family of transcription factors and has been reported to be a candidate tumor suppressor in gastric cancer. However, the association between RUNX3 promoter methylation and gastric cancer remains unclear.

Methods

We systematically reviewed studies of RUNX3 promoter methylation and gastric cancer published in English or Chinese from January 2000 to January 2011, and quantified the association between RUNX3 promoter methylation and gastric cancer using meta-analysis methods.

Results

A total of 1740 samples in 974 participants from seventeen studies were included in the meta-analysis. A significant association was observed between RUNX3 promoter methylation and gastric cancer, with an aggregated odds ratio (OR) of 5.63 (95%CI 3.15, 10.07). There was obvious heterogeneity among studies. Subgroup analyses (including by tissue origin, country and age), meta-regression were performed to determine the source of the heterogeneity. Meta-regression showed that the trend in ORs was inversely correlated with age. No publication bias was detected. The ORs for RUNX3 methylation in well-differentiated vs undifferentiated gastric cancers, and in intestinal-type vs diffuse-type carcinomas were 0.59 (95%CI: 0.30, 1.16) and 2.62 (95%CI: 1.33, 5.14), respectively. There were no significant differences in RUNX3 methylation in cancer tissues in relation to age, gender, TNM stage, invasion of tumors into blood vessel or lymphatic ducts, or tumor stage.

Conclusions

This meta-analysis identified a strong association between methylation of the RUNX3 promoter and gastric cancer, confirming the role of RUNX3 as a tumor suppressor gene.