Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinoma.
BACKGROUND
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 paraffin-embedded 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.
Institute of Oncology Ljubljana, Slovenia.
Blaz
B
Krhin
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia.
Katja
K
Goricar
Institute of Oncology Ljubljana, Slovenia.
Barbara
B
Gazic
Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Slovenia.
Vita
V
Dolzan
Institute of Oncology Ljubljana, Slovenia.
Nikola
N
Besic
Hurthle cell neoplasm; Hurthle cell thyroid carcinoma; antioxidant genes; oxidative stress; thyroid
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