Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm – An association of GPX1 polymorphism and recurrent Hurthle cell carcinoma

Blaz Krhin; Katja Goričar; Barbara Gazić; Vita Dolžan; Nikola Bešić

Blaz Krhin Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana
Katja Goričar Pharmacogenetics Laboratory Institute of Biochemistry Faculty of Medicine University of Ljubljana Vrazov trg 2, 1000 Ljubljana
Barbara Gazić Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana
Vita Dolžan Pharmacogenetics Laboratory Institute of Biochemistry Faculty of Medicine University of Ljubljana Vrazov trg 2, 1000 Ljubljana
Nikola Bešić Institute of Oncology Ljubljana, Zaloška 2, 1000 Ljubljana

Abstract

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 carcinoma (HCC).

Methods. A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCC, Hurthle cell adenoma (HCA) or Hurthle cell nodule (HCN) 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. HCC, HCA and HCN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCC were diagnosed in 20 and 16 HCC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCC, HCA and HCN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCA and HCN group was compared to the HCC group for diagnosis of HCC 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 HCC.