title: 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.
  
  
  CONCLUSIONS
  This meta-analysis confirms that RASSF1A promoter methylation is a risk factor for thyroid tumor.
authors.affiliation: Department of General Practice.
authors.forename: Feiyan
authors.initials: F
authors.lastname: Shou
authors.affiliation: Department of Breast and Thyroid Surgery.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of General Practice.
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.affiliation: Department of Radiology.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Special Inspection Section.
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.affiliation: Department of Cardiovascular Diseases.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Yang
authors.affiliation: Department of Acupuncture and Moxibustion, Shaoxing People's Hospital, Shaoxing, People's Republic of China.
authors.forename: Hongming
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Diseases.
authors.forename: Hangyuan
authors.initials: H
authors.lastname: Guo
keywords: RASSF1A; meta-analysis; methylation; thyroid neoplasms