The Prognostic Role of RASSF1A Promoter Methylation in Breast Cancer: A Meta-Analysis of Published Data

Abstract

PurposeEpigenetic alterations have been investigated as prognostic indicators in breast cancer but their translation into clinical practice has been impeded by a lack of appropriate validation. We present the results of a meta-analysis of the associations between RASSF1A promoter methylation status and both disease free survival (DFS) and overall survival (OS) in female breast cancer.MethodsEligible studies were identified through searching the PubMed, Web of Science and Embase databases. Studies were pooled and summary hazard ratios (HR) with corresponding confidence intervals (CIs) were calculated. Funnel plots were also carried out to evaluate publication bias.ResultsA total of 1795 patients from eight studies were included in the meta-analysis. There are eight studies which investigated DFS in 1795 cases. The relative hazard estimates ranged from 1.77–5.64 with a combined HR of 2.75 (95%CI 1.96–3.84). The HR of RASSF1A promoter methylation on DFS adjusted for other potential prognostic factors was 2.54 (95%CI 1.77–3.66). There has been five trials which analyzed the associations of RASSF1A promoter methylation status with OS in 1439 patients. The hazard estimates ranged from 1.21–6.90 with a combined random-effects estimates of 3.47 (95%CI 1.44–8.34). OS reported in multivariate analysis was evaluated in four series comprising 1346 cases and the summarized random-effects HR estimate was 3.35 (95%CI 1.14–9.85). Additionally, no publication bias was detected for both OS and DFS.ConclusionThe results of this meta-analysis suggest that RASSF1A promoter hypermethylation confers a higher risk of relapse and a worse survival in patients with breast cancer. Large prospective studies are now needed to establish the clinical utility of RASSF1A promoter methylation.

Association Between RASSF1A Promoter Methylation and Testicular Germ Cell Tumor: A Meta-analysis and a Cohort Study

“…Several meta-analysis studies showed an association between RASSF1A promoter hypermethylation and different types of tumors as well as biomarker value of the RASSF1A methylation status (47)(48)(49). This study represents the first meta-analysis of published studies to evaluate the association of RASSF1A promoter hypermethylation with testicular cancer.…”

RASSF1A promoter methylation is associated with increased risk of thyroid cancer: a meta-analysis

“…It has been reported that the CpG methylation of RASSF1A promoter can lead to the loss-of-expression of RASSF1A 14. Previous studies have found that the RASSF1A promoter methylation can increase the risk of lung cancer, breast cancer, prostate cancer, ovarian cancer, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and gastric cancer 17–24. Furthermore, these results indicated that the RASSF1A promoter methylation may be a significant prognostic factor for many human cancers.…”

Lung cancer early detection and health disparities: the intersection of epigenetics and ethnicity

“…Of these genes Cyclin D2 exhibited a stark contrast in frequency between AAs (64%) and Caucasians (19%). While some of these genes may not be linked to prognosis, hypermethylation of Cyclin D2 and RASSF1A are both associated with higher relapse rates and poor overall survival (91)(92)(93).…”