<abstract xmlns="http://www.w3.org/1999/xhtml"><sec><h3>Background</h3><p>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.</p></sec><sec><h3>Patients and methods</h3><p>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 <italic>SOD2</italic> p.Ala16Val, <italic>CAT</italic> c.-262C>T, <italic>GPX1</italic> p.Pro200Leu, <italic>GSTP1</italic> p.Ile105Val, <italic>GSTP1</italic> p.Ala114Val and <italic>GSTM1</italic> and <italic>GSTT1</italic> deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model.</p></sec><sec><h3>Results</h3><p>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.</p></sec><sec><h3>Conclusions</h3><p>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.</p></sec></abstract>

BackgroundThyroid 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.Patients and methodsIn 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.ResultsBetween 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.ConclusionsWe 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.

Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence

Radiology and Oncology

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BackgroundThyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive...

SNP	OR (95% CI)	p
GPX1 (rs1050450)	0.43 (0.07-1.88)	0.344
SOD2 data missing for 2 controls (rs4880)	1.50 (0.36-7.23)	0.754
CAT (rs 1001179)	1.00 (0.27-3.74)	1.000
GSTP1 (rs1695)	1.40 (0.38-5.59)	0.774
GSTP1 (rs 1138272)	1.25 (0.27-6.30)	1.000
GSTM1 (gene deletion) data missing for 1 control	0.43 (0.07-1.88)	0.344
GSTT1 (gene deletion) data missing for 1 control	2.00 (0.29-22.11)	0.687

SNP	Genotype	All patients N (%)	Cases N (%)	Controls N (%)	P_HWE controls
GPX1 rs1050450 p. Pro200Leu	CC	28 (58.3)	16 (66.7)	12 (50)	0.967
	CT	17 (35.4)	7 (29.2)	10 (41.7)
	TT	3 (6.3)	1 (4.2)	2 (8.3)
SOD2 data missing for 2 controls rs4880 p.Val16Ala	GG	10 (21.7)	4 (16.7)	6 (27.3)	0.338
	GA	31 (67.4)	18 (75)	13 (59.1)
	AA	5 (10.9)	2 (8.3)	3 (13.6)
CAT rs1001179 c.-262G>A	GG	32 (66.7)	16 (66.7)	16 (66.7)	0.834
	GA	14 (29.2)	7 (29.2)	7 (29.2)
	AA	2 (4.2)	1 (4.2)	1 (4.2)
GSTP1 rs1695 p.Ile105Val	AA	22 (45.8)	10 (41.7)	12 (50)	0.432
	AG	23 (47.9)	12 (50)	11 (45.8)
	GG	3 (6.3)	2 (8.3)	1 (4.2)
GSTP1 rs1138272 p.Ala114Val	CC	39 (81.3)	19 (79.2)	20 (83.3)	0.106
	CT	8 (16.7)	5 (20.8)	3 (12.5)
	TT	1 (2.1)	/	1 (4.2)
GSTM1b data missing for 1 control gene deletion	non-null	23 (48.9)	14 (58.3)	9 (39.1)
GSTM1b data missing for 1 control gene deletion	null	24 (51.1)	10 (41.7)	14 (60.9)
GSTT1b data missing for 1 control gene deletion	non-null	39 (83)	19 (79.2)	20 (87)
GSTT1b data missing for 1 control gene deletion	null	8 (17)	5 (20.8)	3 (13)

Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence

Article Category: Research Article

Published Online: Feb 16, 2016

Page range: 80 - 86

Received: Feb 02, 2015

Accepted: Feb 23, 2015

DOI: https://doi.org/10.1515/raon-2015-0026

Keywords
secondary thyroid cancer, antioxidant genes, genetic polymorphism

© 2016 Radiol Oncol

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Influence of selected polymorphisms on the risk for secondary thyroid cancer

Genotype frequencies of the antioxidant defence-related genes

Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence

Article Category: Research Article

Published Online: Feb 16, 2016

Page range: 80 - 86

Received: Feb 02, 2015

Accepted: Feb 23, 2015

DOI: https://doi.org/10.1515/raon-2015-0026

Keywordssecondary thyroid cancer, antioxidant genes, genetic polymorphism

© 2016 Radiol Oncol

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Influence of selected polymorphisms on the risk for secondary thyroid cancer

Genotype frequencies of the antioxidant defence-related genes

Keywords
secondary thyroid cancer, antioxidant genes, genetic polymorphism