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.
Highlights
Ovarian cancer is the fifth most common cause of cancer deaths in women and accounts for the highest tumor-related mortality of gynecologic malignancies
Hypermethylation of the tumor suppressor gene (TSG) promoter can lead to gene inactivation, which is critical to the pathogenesis of cancers, and occurs always in the early stage of cancer development in many types of cancer including ovarian cancer [5,6]
A study included in the meta-analysis had to meet the following criteria: 1) studies which evaluated the association of RAS association domain family protein 1a gene (RASSF1A) methylation with ovarian cancer, 2) a case-control study or one including case and control populations, 3) a study reporting the RASSF1A methylation frequency in case and control groups, 4) sample type limited to tissues
Summary
Ovarian cancer is the fifth most common cause of cancer deaths in women and accounts for the highest tumor-related mortality of gynecologic malignancies. Hypermethylation of the tumor suppressor gene (TSG) promoter can lead to gene inactivation, which is critical to the pathogenesis of cancers, and occurs always in the early stage of cancer development in many types of cancer including ovarian cancer [5,6]. Some studies showed that methylation of TSG was detected in tumor tissue and was associated with clinical features [7,8]. The RAS association domain family protein 1a gene (RASSF1A) is one of the tumor suppressor genes (TSG). A number of studies have discussed association between RASSF1A promoter methylation and ovarian cancer. They were mostly based on a small number of samples and showed inconsist results, we conducted a meta-analysis to better identify the association
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