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

Abstract

Objective: Previous studies have reported that Ras-associated domain family 1A (RASSF1A), the most commonly silenced tumor suppressor via promoter methylation, played vital roles in the development of carcinogenesis. The purpose of this meta-analysis was to determine whether RASSF1A promoter methylation increased the risk of thyroid cancer.

Methods: PubMed, Embase, ISI Web of Knowledge, and Chinese National Knowledge Infrastructure databases were searched to obtain eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate the strength of the associations, using Stata 12.0 software. The methodological quality of included studies was evaluated using Newcastle-Ottawa scale table. Egger's test and Begg's test were applied to detect publication biases. TSA 0.9 software was used to calculate the required information size and whether the result was conclusive.

Results: A total of 10 articles with 12 studies that included 422 thyroid cancer patients, identifying the association of RASSF1A promoter methylation with thyroid cancer risk, were collected in this meta-analysis. Overall, RASSF1A promoter methylation significantly increased the risk of thyroid cancer (total, OR=8.27, CI=4.38-15.62, P<0.05; Caucasian, OR=9.25, CI=3.97-21.56, P<0.05; Asian, OR=7.01, CI=2.68-18.38, P<0.05). In the subgroup analysis based on sample type, a significant association between thyroid cancer group and control group was found (normal tissue, OR=9.55, CI=4.21-21.67, P<0.05; adjacent tissue, OR=6.80, CI=2.49-18.56, P<0.05). The frequency of RASSF1A promoter methylation in follicular thyroid carcinoma was higher than in control group (OR=11.88, CI=5.80-24.32, P<0.05). In addition, the results indicated that the RASSF1A promoter methylation was correlated with papillary thyroid carcinoma in Caucasians and Asians (total, OR=8.07, CI=3.54-18.41, P<0.05; Caucasian, OR=11.35, CI=2.39-53.98, P<0.05; Asian, OR=6.67, CI=2.53-17.64, P<0.05). On the basis of the trial sequential analysis, the significant association of RASSF1A promoter methylation with thyroid cancer risk was found, and there was no need to perform further studies.

Conclusion: This meta-analysis confirms that RASSF1A promoter methylation is a risk factor for thyroid tumor.

Keywords: RASSF1A; meta-analysis; methylation; thyroid neoplasms.

Figure 1

Flow chart of study selection procedure.

Figure 2

Forest plot for the association between Ras-associated domain family 1A promoter methylation and risk of thyroid cancer. Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 3

Forest plot for the association between Ras-associated domain family 1A promoter methylation and risk of follicular thyroid carcinoma. Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 4

Forest plot for the association between Ras-associated domain family 1A promoter methylation and risk of papillary thyroid carcinoma. Abbreviations: CI, confidence interval; OR, odds ratio.

Figure 5

Funnel plot of publication biases on the association between Ras-associated domain family 1A promoter methylation and thyroid cancer risk.

Figure 6

Funnel plot of publication biases on the association between Ras-associated domain family 1A promoter methylation and follicular thyroid carcinoma risk.

Figure 7

Funnel plot of publication biases on the association between Ras-associated domain family 1A promoter methylation and papillary thyroid carcinoma risk.

Figure 8

Trial sequential analysis comparing the Ras-associated domain family 1A promoter methylation frequency of control group and thyroid cancer group. Abbreviation: RIS, required information size.