Association of HOTAIR, MIR155HG, TERC, miR-155,-196a2, and-146a Genes Polymorphisms with Papillary Thyroid Cancer Susceptibility and Prognosis

Simple Summary Although papillary thyroid carcinoma (PTC) has a relatively indolent behavior, the clinical course in patients with recurrent or metastatic disease is still unfavorable. Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in PTC. Thus, we evaluated the association of HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 polymorphisms with the PTC risk and prognosis, in 102 PTC patients and 106 controls. Our results showed that the HOTAIR rs920778 polymorphism is associated with an increased PTC risk, as well as with lymph node metastasis, recurrence, and progression-free survival. Multivariate Cox regression revealed that ATA risk and HOTAIR rs920778 polymorphism are independent prognostic factors in PTC. In addition, we observed a novel association of the MIR155HG rs1893650 polymorphism with the reduced PTC risk. Polymorphisms in HOTAIR and MIR155HG genes could potentially be new biomarkers for risk assessment and prognosis in PTC patients.Abstract Polymorphisms in long non-coding RNA and microRNA genes may play a significant role in the susceptibility and progression of papillary thyroid carcinoma (PTC). The current study investigates the polymorphisms HOTAIR rs920778, MIR155HG rs1893650, TERC rs10936599, miR-155 rs767649, miR-196a2 rs11614913 and miR-146a rs2910164 in 102 PTC patients and 106 age- and sex-matched controls of the Caucasian Serbian population, using real-time PCR. We observed differences in genotype distributions of the HOTAIR rs920778 (p = 0.016) and MIR155HG rs1893650 (p = 0.0002) polymorphisms between PTC patients and controls. HOTAIR rs920778 was associated with increased PTC susceptibility (adjusted OR = 1.497, p = 0.021), with the TT variant genotype increasing the risk compared to the CC genotype (OR = 2.466, p = 0.012) and C allele carriers (CC + CT) (OR = 1.585, p = 0.006). The HOTAIR rs920778 TT genotype was associated with lymph node metastasis (p = 0.022), tumor recurrence (p = 0.016), and progression-free survival (p = 0.010) compared to C allele carriers. Multivariate Cox regression revealed that ATA risk (HR = 14.210, p = 0.000004) and HOTAIR rs920778 (HR = 2.811, p = 0.010) emerged as independent prognostic factors in PTC. A novel polymorphism, MIR155HG rs1893650, was negatively correlated with susceptibility to PTC, with TC heterozygotes exerting a protective effect (OR = 0.268, p = 0.0001). These results suggest that the polymorphisms HOTAIR rs920778 and MIR155HG rs1893650 could be potential prognostic and risk biomarkers in papillary thyroid carcinomas.