title: Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence.
abstract: BACKGROUND
  Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence.
  
  
  METHODS
  In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model.
  
  
  RESULTS
  Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer.
  
  
  CONCLUSIONS
  We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.
authors.affiliation: Department of Radiation Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Ana Lina
authors.initials: AL
authors.lastname: Vodusek
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Katja
authors.initials: K
authors.lastname: Goricar
authors.affiliation: Department of Pathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia.
authors.forename: Barbara
authors.initials: B
authors.lastname: Gazic
authors.affiliation: Pharmacogenetics Laboratory, Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia.
authors.forename: Vita
authors.initials: V
authors.lastname: Dolzan
authors.affiliation: Department of Hematology and Oncology, University Children's Hospital, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Jazbec
keywords: antioxidant genes; genetic polymorphism; secondary thyroid cancer