Author/Editor     Krhin, Blaž; Goričar, Katja; Gazić, Barbara; Dolžan, Vita; Bešić, Nikola
Title     Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma
Type     članek
Publication year     2016
Volume     str. [1-8]
ISSN     1318-2099 - Radiology and oncology
Language     eng
Abstract     Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). Methods. A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffinembedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. Results. HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). Conclusions. GPX1 polymorphism may influence the risk for recurrent disease in HCTC.Za Huerthlejeve celice ščitnice je značilno veliko število mitohondrijev in oksidativnih encimov. Ker povečan oksidativni metabolizem lahko vodi v povečan oksidativni stres oziroma ga lahko povezujemo z večjo verjetnostjo razvoja raka, smo v naši raziskavi preverjali, ali obstaja povezava med funkcionalnimi polimorfizmi antioksidativnih genov (SOD2, CAT, GPX, GSTP1, GSTM1 in GSTT1) in nastankom ali kliničnim potekom raka Huerthlejevih celic ščitnice (HCTC). Bolniki in metode. Retrospektivno raziskavo smo izvedli pri 139 bolnikih, pri katerih smo zaradi suma na neoplazmo Huerthlejevih celic ščitnice opravili operacijo ščitnice. Diagnozo HCTC, adenoma Huerthlejevih celic ščitnice (HCTA) ali gomolja Huerthlejevih celic ščitnice (HCTN) smo postavili s histopatomorfološko analizo. DNA smo izolirali iz stebričkov histološko potrjenega zdravega dela ščitnice, pridobljenega iz arhiviranih parafinskih blokov tumorjev, fiksiranih v formalinu. S postopki genotipizacije smo določali prisotnost polimorfizmov v antioksidativnih genih. Z logistično regresijo pa smo primerjali porazdelitve posameznih genotipov med različnimi skupinami bolnikov. Rezultati. HCTC smo ugotovili pri 53, HCTA pri 47 in HCTN pri 21 bolnikih. Pri 20 bolnikih s HCTC smo ugotovili prisotnost zasevkov, pri 16 pa ponovitev bolezni. Pri skupinah bolnikov s HCTC, HCTA in HCTN frekvence genotipov in alelov preučevanih polimorfizmov niso odstopale od Hardy-Weinbergovega ravnotežja. Dominantni genetski model ni pokazal povezave med porazdelitvijo frekvenc genotipov preučevanih polimorfizmov in prisotnostjo HCTC v primerjavi s HCTA in HCTN, prav tako ni bilo povezave s prisotnostjo zasevkov pri HCTC. Ugotovili pa smo povezavo med polimorfizmom GPX1 in ponovitvijo HCTC (p = 0,040). Polimorfizem GPX1 lahko vpliva na možnost ponovitve HCTC.
Keywords     rak Huerthlejevih celic ščitnice
neoplazma Huerthlejevih celic
ščitnica
oksidativni stres
Hurthle cell thyroid carcinoma
Hurthle cell neoplasm
thyroid
oxidative stress