Association between Ras association domain family 1A promoter methylation and esophageal squamous cell carcinoma: a meta-analysis.

Jian-Zhou Yang,Zhong-Yi Chen,Ai-Fang Ji,Shi Wu Wen,Jin-Sheng Wang

doi:10.7314/apjcp.2014.15.9.3921

Abstract

RASSF1A has been reported to be a candidate tumor suppressor in esophageal squamous cell carcinoma (ESCC). However, the association between RASSF1A promoter methylation and ESCC remains unclear. Eligible studies were identified through searching PubMed, Medline, Web of Science, and the China National Knowledge Infrastucture database. Studies were pooled and odds ratios (ORs) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also performed to evaluate publication bias. Twelve studies involving 859 cases and 675 controls were included in this meta-analysis. A significant association was observed between RASSF1A methylation and ESCC overall (OR = 11.7, 95% CI: 6.59-20.9, z=8.36, P<0.00001). Subgroup analysis showed that the OR for heterogeneous tissues was 5.35 (95% CI = 2.95-9.71) while for autologous tissues it was 16.0 (8.31-30.96). For patient sample size, the OR for the <50 subgroup was 9.92 (95% CI = 2.88-34.2) and for the 50 case group was 13.1 (95% CI = 6.59-25.91). The OR for a relationship between RASSF1A methylation and TNM stages was 0.27 (95% CI=0.10-0.77), whereas there were no significant differences in RASSF1A methylation in relation to gender and differentiation among ESCC cases. This meta-analysis suggests a significant association between RASSF1A methylation and ESCC.

Highlights

Esophageal carcinoma is the eighth most common cancer in the world and the seventh leading cause of cancer death worldwide (Jemal et al, 2011)
The frequencies of RASSF1A promoter methylation ranged from 14.89% to 67.50% in esophageal squamous cell carcinoma (ESCC) tissues and 0.0% to 16.13% in normal tissues, respectively
The pooled odds ratios (ORs) for RASSF1A methylation in cancer tissues compared with normal tissues was 11.73 (95%confidence intervals (CIs) 6.5920.89, z=8.36, P

Summary

Introduction

Esophageal carcinoma is the eighth most common cancer in the world and the seventh leading cause of cancer death worldwide (Jemal et al, 2011). Esophageal cancer may be divided into two major histological subtypes: esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EADC). ESCC is the predominant histological subtype, comprising 70% of esophageal cancer in the world and this tumor type is especially prevalent in East Asia, South Asia and South Africa (Parkin et al, 2000). DNA methylation of tumor suppressor gene (TSG) leading to transcriptional inactivation has been identified as an important mechanism in many carcinogenesis including ESCC. The results of some studies indicated that methylation of TSG was detected in tumor tissue and was associated with clinical features (Teodoridis et al, 2005; Bondurant et al., 2011). Some studies have reported differences in the methylation frequencies of RASSF1A between ESCC cancer tissues and non-

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Conclusion