Background The 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. Methods Eligible 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. Results Thirteen 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. Conclusion The results suggested that RASSF1A promoter methylation had a strong association with ovarian cancer.
Barnholtz-Sloan JS, Schwartz AG, Qureshi F, Jacques S, Malone J, et al. (2003) Ovarian cancer: changes in patterns at diagnosis and relative survival over the last three decades. Am J Obstet Gynecol 189: 1120–1127.
Bondurant AE, Huang Z, Whitaker RS, Simel LR, Berchuck A, et al. (2011) Quantitative detection of RASSF1A DNA promoter methylation in tumors and serum of patients with serous epithelial ovarian cancer. Gynecol Oncol 123: 581–587.
Imura M, Yamashita S, Cai LY, Furuta J, Wakabayashi M, et al. (2006) Methylation and expression analysis of 15 genes and three normally-methylated genes in 13 Ovarian cancer cell lines. Cancer Lett 241: 213–220.
Wu Q, Lothe RA, Ahlquist T, Silins I, Trope CG, et al. (2007) DNA methylation profiling of ovarian carcinomas and their in vitro models identifies HOXA9, HOXB5, SCGB3A1, and CRABP1 as novel targets. Mol Cancer 6: 45.
Ibanez de Caceres I, Battagli C, Esteller M, Herman JG, Dulaimi E, et al. (2004) Tumor cell-specific BRCA1 and RASSF1A hypermethylation in serum, plasma, and peritoneal fluid from ovarian cancer patients. Cancer Res 64: 6476–6481.
Shen WJ, Dai DQ, Guo KJ, Li XM (2008) RASSF1A and BRCA1 and p16 gene aberrant methylation detection and its clinical significance in epithelial ovarian cancer. Chinese Journal of Cancer Prevention and Treatment 15: 530–533.
Burbee DG, Forgacs E, Zochbauer-Muller S, Shivakumar L, Fong K, et al. (2001) Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst 93: 691–699.
Kuroki T, Trapasso F, Yendamuri S, Matsuyama A, Alder H, et al. (2003) Allele loss and promoter hypermethylation of VHL, RAR-beta, RASSF1A, and FHIT tumor suppressor genes on chromosome 3 p in esophageal squamous cell carcinoma. Cancer Res 63: 3724–3728.