Abstract
BackgroundThis study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene and postoperative recurrence in patients with thyroid carcinoma (TC).MethodsA total of 312 patients diagnosed with TC were chosen for the study and categorized into recurrence (n = 75) and non-recurrence (n = 237) groups. The hTERT rs2736100 and rs2736098 polymorphisms were detected by performing polymerase chain reaction-restriction fragment length polymorphism. DNA methylation in the promoter region of hTERT gene was evaluated by pyrosequencing. A telephonic and/or outpatient follow-up was conducted for all patients. The correlations of DNA methylation and polymorphisms in the promoter region of hTERT with postoperative recurrence of TC patients underwent analysis.ResultsThe patient in the recurrence group showed evidently different pathological types and tumor stages in comparison to the non-recurrence group. The GG genotype of hTERT rs2736100 might increase the recurrence risk of TC patients. No correlations between hTERT rs2736098 polymorphisms and recurrence risk were observed. Compared to the TT + TG genotype frequency, the rs2736100 GG genotype frequency increased in patients without multicentricity, patients with extrathyroidal invasion, patients with lymph node metastasis, patients with undifferentiated carcinoma, and patients in the III + IV stage. The recurrence group showed significantly higher DNA methylation level compared to the non-recurrence group. The DNA methylation level was closely associated to tumor stage and lymph node metastasis of TC patients in the recurrence group.ConclusionsThe DNA methylation and rs2736100 polymorphisms in the promoter region of hTERT gene might be in correlation to postoperative recurrence of TC patients.
Highlights
This study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase gene and postoperative recurrence in patients with thyroid carcinoma (TC)
The pathological type and tumor stage of the recurrence group were different in comparison to the nonrecurrence group, which indicated that the postoperative recurrence of TC might be associated to the pathological type and tumor stage
Our findings have provided evidence that rs2736100 polymorphism and DNA methylation in the promoter region of the human telomerase reverse transcriptase (hTERT) gene is correlated to the prognosis of TC after surgery
Summary
This study aims at exploring the correlations between DNA methylation and polymorphisms in the promoter region of the human telomerase reverse transcriptase (hTERT) gene and postoperative recurrence in patients with thyroid carcinoma (TC). Thyroid carcinoma (TC) is an uncommon form of carcinoma but is one of the most common malignancies in the human endocrine system [1]. It accounts for about 2% of newly diagnosed carcinoma cases and a majority of deaths related to human endocrine carcinoma every year [2]. A neck dissection is usually a safe therapeutic treatment for TC patients but can induce some complications [5]. The increasing evidence suggested that the common variant in the DNA sequence, especially single-nucleotide polymorphisms (SNPs), is commonly associated to the efficacy of surgical treatment [7]
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