Promoter methylation of p16 and RASSF1A genes may contribute to the risk of papillary thyroid cancer: A meta-analysis

Abstract

The aim of the present meta-analysis was to investigate the correlation of promoter methylation of the p16 and Ras association domain family 1 isoform A (RASSF1A) genes with the risk of the development of papillary thyroid cancer (PTC). A number of electronic databases were searched without language restrictions as follows: Medline (1966-2013), the Cochrane Library database (Issue 12, 2013), Embase (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013). A meta-analysis was performed with the use of Stata statistical software. The odds ratios (ORs), ratio differences (RDs) and 95% confidence intervals (95% CIs) were calculated. In the present meta-analysis, eleven clinical cohort studies with a total of 734 patients with PTC were included. The results of the current meta-analysis indicated that the frequency of promoter methylation of p16 in cancer tissues was significantly higher compared with that in normal, adjacent and benign tissues (cancer tissues vs. normal tissues: OR=7.14; 95% CI, 3.30-15.47; P<0.001; cancer tissues vs. adjacent tissues: OR=11.90; 95% CI, 5.55-25.52; P<0.001; cancer tissues vs. benign tissues: OR=2.25; 95% CI, 1.67-3.03; P<0.001, respectively). The results also suggest that RASSF1A promoter methylation may be implicated in the pathogenesis of PTC (cancer tissues vs. normal tissues: RD=0.53; 95% CI, 0.42-0.64; P<0.001; cancer tissues vs. adjacent tissues: RD=0.39; 95% CI, 0.31-0.48; P<0.001; cancer tissues vs. benign tissues: RD=0.39; 95% CI, 0.31-0.47; P<0.001; respectively). Thus, the present meta-analysis indicates that aberrant promoter methylation of p16 and RASSF1A genes may play a crucial role in the pathogenesis of PTC.

Meta-analysis of promoter methylation in eight tumor-suppressor genes and its association with the risk of thyroid cancer

“…The hypermethylation of TSG promoter suppresses genes expression by inhibiting transcription, thereby affecting cell signaling pathways. Two previous meta-analyses demonstrated the association between RASSF1A promoter methylation and PTC risk [ 31 , 41 ]. In the current report, a comprehensive review was carried out to determine the relationship between thyroid cancer susceptibility and gene methylation.…”

“…In some studies, RASSF1 promoter inactivation has been detected in more than 30% of thyroid tumors, representing the most and frequent event in thyroid cancers [ 72 , 73 ]; however, in some reports, no significant correlation between RASSF1 methylation and thyroid cancer risk was detected [ 68 , 74 – 78 ]. In two prior meta-analyses, researchers only examined the association between RASSF1 promoter methylation and PTC risk [ 31 , 41 ]. Although the results of these prior meta-analyses demonstrated that the frequency of RASSF1 promoter methylation was significantly associated with increased risk of thyroid cancer, our study showed that the influence of RASSF1 promoter methylation was lower than those of CDH1 and SLC5A8 promoter methylation.…”

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

“…Thus, it is necessary to conduct a meta-analysis to determine the strength of association between RASSF1A promoter methylation and thyroid cancer. In the literature retrieval, a previous meta-analysis was found 45. However, the meta-analysis only explored the association between RASSF1A promoter methylation and PTC risk, and no clinical information was included.…”

Research Progress of DNA Methylation in Thyroid Cancer

“…Studies indicated RASSF1A methylation differed in PTC compared with normal thyroid and was correlated with extracapsular invasion inversely. It suggested that RASSF1A has a potential role as a molecular marker for characterization of PTC histopathology [11][12][13][14][15]. It is shown that hypermethylation of RASSF1A promoter region is 20-32% in PTC.…”