Adomas Bunevicius1,2,3, Edward R Laws4,5, Ausra Saudargiene6, Arimantas Tamasauskas6, Giorgio Iervasi7, Vytenis Deltuva6, Timothy R Smith4,5, Robertas Bunevicius8. 1. Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania. a.bunevicius@yahoo.com. 2. Brigham and Women's Hospital, Boston, MA, USA. a.bunevicius@yahoo.com. 3. Harvard University, Boston, MA, USA. a.bunevicius@yahoo.com. 4. Brigham and Women's Hospital, Boston, MA, USA. 5. Harvard University, Boston, MA, USA. 6. Neuroscience Institute, Lithuanian University of Health Sciences, Kaunas, Lithuania. 7. CNR - Institute of Clinical Physiology, Pisa, Italy. 8. Lithuanian University of Health Sciences, Kaunas, Lithuania.
Abstract
BACKGROUND: Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumor patients. METHODS: Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017. RESULTS: In glioblastoma patients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13-0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20-8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningioma patients, indicating greater T4 to T3 conversion. CONCLUSIONS: SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastoma patients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.
BACKGROUND: Thyroid hormone (TH) metabolism can have prognostic significance in brain tumors. We studied the association of common variations in three deiodinase gene single-nucleotide polymorphisms (SNPs) with circulating TH concentrations and prognosis of brain tumorpatients. METHODS:Patients admitted for glioma and meningioma surgery between January, 2010 and September, 2011 were evaluated for functional status (Barthel Index or BI) and circulating free tri-iodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) concentrations. Ten common SNPs in the DIO1 gene; five SNPs in the DIO2 gene; and one SNP in the DIO3 gene were genotyped. Follow-up continued until November, 2017. RESULTS: In glioblastomapatients, the DIO1 SNP rs2235544 CC genotype was associated with significantly lower risk of death at 2 years when compared to AA + CA genotypes after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, and extent of resection (HR = 0.34, 95% CI: 0.13-0.84, p = 0.019). The TT genotype vs. CC + TC genotypes of the DI02 SNP rs12885300 was associated with increased mortality risk after adjusting for patient gender, age, pre-operative functional status, adjuvant therapy, extent of resection, and FT3/FT4 (HR = 3.13, 95% CI: 1.20-8.16, p < 0.019). The C-allele of the DI01 SNP rs2235544 was related to increased circulating free T3/ free T4 ratio in glioma and meningiomapatients, indicating greater T4 to T3 conversion. CONCLUSIONS: SNPs of DIO1 gene (rs2235544) and DIO2 gene (rs12885300) have independent prognostic significance in glioblastomapatients. The C-allele of the DIO1 (rs2235544) is associated with greater T4 to T3 conversion.
Authors: Adomas Bunevicius; Vytenis Pranas Deltuva; Sarunas Tamasauskas; Timothy Smith; Edward R Laws; Robertas Bunevicius; Giorgio Iervasi; Arimantas Tamasauskas Journal: Oncotarget Date: 2017-01-31