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

• Published in: PloS one 2017-09, Vol.12 (9), p.e0184892
• Main Authors: Khatami, Fatemeh, Larijani, Bagher, Heshmat, Ramin, Keshtkar, Abbasali, Mohammadamoli, Mahsa, Teimoori-Toolabi, Ladan, Nasiri, Shirzad, Tavangar, Seyed Mohammad
• Format: Article
• Language: English
• Subjects: Bias; Biology and Life Sciences; Cadherins - genetics; Cancer; Carcinogenesis; Carcinogens; Confidence intervals; Databases, Factual; DNA Methylation; E-cadherin; Genes; Genes, Tumor Suppressor; Health risks; Humans; Medical ethics; Medicine and Health Sciences; Meta-analysis; Methylation; Mutation; Odds Ratio; Pathology; Physical Sciences; Promoter Regions, Genetic; PTEN Phosphohydrolase - genetics; PTEN protein; Research and Analysis Methods; Risk; Science Policy; Sensitivity analysis; Studies; Thyroid; Thyroid cancer; Thyroid Neoplasms - etiology; Thyroid Neoplasms - genetics; Thyroid-stimulating hormone receptors; Tumor suppressor genes; Tumor Suppressor Proteins - genetics
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184892

Promoter methylation in a number of tumor-suppressor genes (TSGs) can play crucial roles in the development of thyroid carcinogenesis. The focus of the current meta-analysis was to determine the impact of promoter methylation of eight selected candidate TSGs on thyroid cancer and to identify the most important molecules in this carcinogenesis pathway. A comprehensive search was performed using Pub Med, Scopus, and ISI Web of Knowledge databases, and eligible studies were included. The methodological quality of the included studies was evaluated according to the Newcastle Ottawa scale table and pooled odds ratios (ORs); 95% confidence intervals (CIs) were used to estimate the strength of the associations with Stata 12.0 software. Egger's and Begg's tests were applied to detect publication bias, in addition to the "Metatrim" method. A total of 55 articles were selected, and 135 genes with altered promoter methylation were found. Finally, we included eight TSGs that were found in more than four studies (RASSF1, TSHR, PTEN, SLC5A, DAPK, P16, RARβ2, and CDH1). The order of the pooled ORs for these eight TSGs from more to less significant was CDH1 (OR = 6.73), SLC5 (OR = 6.15), RASSF1 (OR = 4.16), PTEN (OR = 3.61), DAPK (OR = 3.51), P16 (OR = 3.31), TSHR (OR = 2.93), and RARβ2 (OR = 1.50). Analyses of publication bias and sensitivity confirmed that there was very little bias. Thus, our findings showed that CDH1 and SCL5A8 genes were associated with the risk of thyroid tumor genesis.