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

	HCTA + HCTN	HCTC
Number [N] (%)	68 (56.2)	53 (43.8)
Median age [years] (range )	49.5 (38.5–57.8)	62 (45.5–70.5)
Gender F/M [N] (%)	58/10 (85.3/14.7)	37/16 (69.8/30.2)
Median tumor diameter [mm] (range )	26.0 (16.0–34.8)	40.0 (25.5–65.0)
Metastasis (%)	/	20 (37.7)
Recurrence (%)	/	16 (30.2)
Concomitant disease N (%)	16 (23.5)	20 (37.7)
Hashimoto thyroiditis	11 (16.2)	12 (22.6)
Diabetes mellitus	1 (1.5)	7 (13.2)
Graves’ disease	2 (2.9)	3 (5.7)
Non-thyroid Malignancy	2 (2.9)	2 (3.8)

F= female; HCTA = Hurthle cell thyroid adenoma; HCTC = Hurthle cell thyroid carcinoma; HCTN = Hurthle cell thyroid nodule; M = male

Table 2

Association of clinical and demographic characteristics with Hurthle cell thyroid neoplasms, metastatic disease and recurrent disease

	HCTA+HCTN versus HCTC		Metastatic disease		Recurrent disease
	OR (95% CI)	pa	OR (95% CI)	pa	OR (95% CI)	pa
Gender	2.51 (1.03–6.12)	0.043	2.08 (0.63–6.90)	0.230	2.42 (0.70–8.37)	0.163
Age	1.04 (1.01–1.06)	0.004	1.07 (1.02–1.12)	0.005	1.05 (1.01–1.10)	0.026
Tumor diameter	1.05 (1.02–1.07)	< 0.001	1.09 (1.04–1.14)	< 0.001	1.04 (1.01–1.07)	0.005
Concomitant disease	1.97 (0.90–4.34)	0.092	0.83 (0.26–2.63)	0.749	0.83 (0.26–2.63)	0.523

CI = confidence interval; HCTA = Hurthle cell thyroid adenoma; HCTC = Hurthle cell thyroid carcinoma; HCTN = Hurthle cell thyroid nodule; OR = odds ratio;

a = p less than 0.05 was considered statistically significant

Table 3

Genotype frequencies in patients with Hurthle cell neoplasms

Gene	Polymorphism	Genotype	All patients (%)	P_HWE	HCTA+HCTN (%)	HCTC (%)
SOD2	rs4880; c.47C>T; p.Val16Ala	CC	26 (21.7)	0.903	12 (17.9)	14 (26.4)
		CT	59 (49.2)		34 (50.7)	25 (47.2)
		TT	35 (29.2)		21 (31.3)	14 (26.4)
CAT	rs1001179; c.-262C>T; c.-262G>A	CC	70 (58.3)	0.907	35 (52.2)	35 (66.0)
		CT	43 (35.8)		30 (44.8)	13 (24.5)
		TT	7 (5.8)		2 (3)	5 (9.4)
GPX1	rs1050450; c.599C>T; p.Pro200Leu	CC	63 (52.1)	0.424	35 (51.5)	28 (52.8)
		CT	51 (42.1)		32 (47.1)	19 (35.8)
		TT	7 (5.8)		1 (1.5)	6 (11.3)
GSTP1	rs1695; c.341C>T; p.Ile105Val	CC	54 (44.6)	0.653	28 (41.2)	26 (49.1)
		CT	52 (43.0)		32 (47.1)	20 (37.7)
		TT	15 (12.4)		8 (11.8)	7 (13.2)
GSTP1	rs1138272; c.313A>G; p.Ala114Val	AA	103 (85.1)	0.159	58 (85.3)	45 (84.9)
		AG	16 (13.2)		8 (11.8)	8 (15.1)
		GG	2 (1.7)		2 (2.9)	0 (0)
GSTM1	Gene deletion	Wild type	55 (50.9)	/a	33 (50.8)	22 (51.2)
GSTM1	Gene deletion	Gene deletion	53 (49.1)		32 (49.2)	21 (48.8)
GSTT1	Gene deletion	Wild type	93 (86.1)	/a	54 (83.1)	39 (90.7)
GSTT1	Gene deletion	Gene deletion	15 (13.9)		11 (16.9)	4 (9.3)

HCTA = Hurthle cell thyroid adenoma; HCTC = Hurthle cell thyroid carcinoma; HCTN = Hurthle cell thyroid nodule; HWE = Hardy-Weinberg equilibrium

a HWE could not be evaluated for GSTM1 and GSTT1 as we were not able to distinguish between carriers of one or two copies of each gene.

Table 4

Association of SOD2, CAT, GPX1 and GST polymorphisms with diagnosis of Hurthle cell neoplasm, presence of metastatic disease and occurrence of recurrent disease

Gene	Genotype	Diagnosis (HCTA+HCTN vs. HCTC)				Metastatic disease				Recurrent disease
Gene	Genotype	OR (95% CI)	pa	OR-adjb (95% CI)	p-adjb	OR (95% CI)	pa	OR-adjb (95% CI)	p-adjb	OR (95% CI)	pa	OR-adjb (95% CI)	p-adjb
SOD2	CC	0.61	0.264	0.65	0.373	1.12	0.856	0.72	0.706	1.11	0.878	0.82	0.788
rs4880	CT+TT	(0.25–1.46)	0.264	(0.25–1.67)	0.373	(0.32–4.00)	0.856	(0.12–4.09)	0.706	(0.29–4.26)	0.878	(0.18–3.62)	0.788
CAT	CC	0.56	0.129	0.81	0.600	0.34	0.102	0.57	0.499	1.25	0.721	2.95	0.155
rs1001179	CT+TT	(0.27–1.18)	0.129	(0.36–1.81)	0.600	(0.09–1.24)	0.102	(0.11–2.91)	0.499	(0.37–4.25)	0.721	(0.66–13.1)	0.155
GPX1	CC	0.95	0.882	1.02	0.962	0.63	0.417	0.72	0.682	0.25	0.040	0.19	0.036
rs1050450	CT+TT	(0.46–1.94)	0.882	(0.46–2.24)	0.962	(0.20–1.93)	0.417	(0.15–3.52)	0.682	(0.07–0.94)	0.040	(0.04–0.89)	0.036
GSTP1	CC	0.73	0.388	0.82	0.628	1.30	0.646	2.40	0.291	0.46	0.202	0.49	0.300
rs1695	CT+TT	(0.35–1.50)	0.388	(0.37–1.82)	0.628	(0.43–3.96)	0.646	(0.47–12.13)	0.291	(0.14–1.52)	0.202	(0.13–1.89)	0.300
GSTP1	AA	1.03	0.952	1.15	0.800	0.99	0.988	1.24	0.836	0.29	0.261	0.24	0.244
rs1138272	AG+GG	(0.38–2.83)	0.952	(0.39–3.45)	0.800	(0.21–4.67)	0.988	(0.17–9.19)	0.836	(0.03–2.54)	0.261	(0.02–2.64)	0.244
GSTM1	Wild type Gene deletion	0.98 (0.46–2.13)	0.968	0.91 (0.39–2.12)	0.819	1.59 (0.47–5.39)	0.456	1.40 (0.23–8.57)	0.716	1.32 (0.38–4.64)	0.666	1.24 (0.28–5.41)	0.774
GSTT1	Wild type Gene deletion	0.50 (0.15–1.70)	0.269	0.44 (0.11–1.82)	0.257	1.44 (0.18–11.29)	0.730	0.83 (0.02–39.34)	0.923	2.00 (0.25–15.85)	0.512	1.42 (0.1–20.98)	0.798

CI = confidence interval; HCTA = Hurthle cell thyroid adenoma; HCTC = Hurthle cell thyroid carcinoma; HCTN = Hurthle cell thyroid nodule; OR = odds ratio;

a = p less than 0.05 was considered statistically significant;

b = adjusted for tumor diameter

a = p less than 0.05 was considered statistically significant;

b = adjusted for tumor diameter

a = p less than 0.05 was considered statistically significant;

b = adjusted for tumor diameter

Table 5

Association of GSTP1 haplotypes and diagnosis of Hurthle cell neoplasm, presence of metastatic disease and occurrence of recurrent disease

Haplotype	Estimated frequency	Diagnosis (HCTA+HCTN vs. HCTC)		Metastatic disease		Recurrent disease
Haplotype	Estimated frequency	OR (95% CI)	pa	OR (95% CI)	pa	OR (95% CI)	pa
AC	0.68	Reference		Reference		Reference
GC	0.25	0.88 (0.49–1.60)	0.686	1.04 (0.38–2.86)	0.935	0.45 (0.13–1.64)	0.230
GT	0.07	0.83 (0.33–2.13)	0.704	0.99 (0.21–4.72)	0.988	028 (0.03–2.89)	0.288

CI = confidence interval.; HCTC = Hurthle cell thyroid carcinoma; HCTA = Hurthle cell thyroid adenoma; HCTN = Hurthle cell thyroid nodule; OR = odds ratio

a - p less than 0.05 was considered statistically significant

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DOI: https://doi.org/10.1515/raon-2016-0031 | Journal eISSN: 1581-3207 | Journal ISSN: 1318-2099

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Language: English

Page range: 289 - 296

Submitted on: Jan 4, 2016

Accepted on: May 2, 2016

Published on: Jul 19, 2016

Published by: Association of Radiology and Oncology

In partnership with: Paradigm Publishing Services

Publication frequency: 4 issues per year

Keywords:

Hurthle cell thyroid carcinoma,

Hurthle cell neoplasm,

thyroid,

Related subjects:

© 2016 Blaz Krhin, Katja Goricar, Barbara Gazic, Vita Dolzan, Nikola Besic, published by Association of Radiology and Oncology
This work is licensed under the Creative Commons License.

Volume 50 (2016): Issue 3 (September 2016)