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

Authors Shou FY, Xu F, Li G, Zhao ZH, Mao Y, Yang FF, Wang HM, Guo HY

Received 11 October 2016

Accepted for publication 8 November 2016

Published 9 January 2017 Volume 2017:10 Pages 247—257

DOI https://doi.org/10.2147/OTT.S124417

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 2

Editor who approved publication: Dr Ingrid Espinoza

Feiyan Shou,1,* Feng Xu,2,* Gang Li,1 Zhenhua Zhao,3 Ying Mao,4 Fangfang Yang,5 Hongming Wang,6 Hangyuan Guo5

1Department of General Practice, 2Department of Breast and Thyroid Surgery, 3Department of Radiology, 4Department of Special Inspection Section, 5Department of Cardiovascular Diseases, 6Department of Acupuncture and Moxibustion, Shaoxing People’s Hospital, Shaoxing, People’s Republic of China

*These authors contributed equally to this work

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, methylation, thyroid neoplasms, meta-analysis

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