Association between RASSF1A Promoter Methylation and Ovarian Cancer: A Meta-Analysis

Abstract

BackgroundThe RAS association domain family protein 1a gene (RASSF1A) is one of the tumor suppressor genes (TSG). Inactivation of RASSF1A is critical to the pathogenesis of cancer. Aberrant TSG methylation was considered an important epigenetic silencing mechanism in the progression of ovarian cancer. A number of studies have discussed association between RASSF1A promoter methylation and ovarian cancer. However, they were mostly based on a small number of samples and showed inconsist results, Therefore, we conducted a meta-analysis to better identify the association.MethodsEligible studies were identified by searching the PubMed, EMBASE, Web of Science, and CNKI databases using a systematic searching strategy. We pooled the odds ratio (ORs) from individual studies using a fixed-effects model. We performed heterogeneity and publication bias analysis simultaneously.ResultsThirteen studies, with 763 ovarian cancer patients and 438 controls were included in the meta-analysis. The frequencies of RASSF1A promoter methylation ranged from 30% to 58% (median is 48%) in the cancer group and 0 to 21% (median is 0) in the control group. The frequencies of RASSF1A promoter methylation in the cancer group were significantly higher than those in the control group. The pooled odds ratio was 11.17 (95% CI = 7.51–16.61) in the cancer group versus the corresponding control group under the fixed-effects model.ConclusionThe results suggested that RASSF1A promoter methylation had a strong association with ovarian cancer.

Relationship between RAS Association Domain Family Protein 1A Promoter Methylation and the Clinicopathological Characteristics in Patients with Ovarian Cancer: A Systematic Meta-Analysis

“…RASSF1A promoter methylation may play a crucial role in ovarian cancer carcinogenesis in the comparison of ovarian cancer and nonmalignant tissues [20, 52]. However, the correlation of RASSF1A promoter methylation between ovarian cancer and LMP tumors remains to be evaluated.…”

“…Previous meta-analysis only evaluated the relationship between RASSF1A promoter methylation and ovarian cancer in cancer versus nonmalignant controls [20]. Borderline ovarian tumors, also called tumors of low malignant potential (LMP), are defined histologically by proliferation of atypical cells [21].…”

Molecular Epigenetics in the Management of Ovarian Cancer: Are We Investigating a Rational Clinical Promise?

“…The promoter methylation of RASSF1A is highly associated with ovarian cancer (34). RASSF1A binds to tubulin and promotes microtubule polymerization and stabilization (102, 103).…”

Development of a multiplex MethyLight assay for the detection of DAPK1 and SOX1 methylation in epithelial ovarian cancer in a north Indian population

“…Aberrant DNA methylation is a very stable repressive mark of DNA which is commonly associated with the loss of gene function (Antiquera and Bird, 1999). Numerous reports indicate that methylation at CpG islands in the promoter region is the major cause of silencing of many tumor suppressor genes, such as RASSF1A, DAPK1, p16 and GBGT1, in various cancers (Collins et al, 2006;Bammidi et al, 2012;Matoo et al, 2013;Shi et al, 2013;Bhagat et al, 2014;Jacob et al, Edited by Rimantas Kodzius2014). Its high stability and sensitivity of detection make DNA methylation an attractive clinical tool for the diagnosis of different cancers, prediction of potential malignancy progression and metastasis/recurrence of cancer.…”