Common genetic variants in pituitary-thyroid axis genes and the risk of differentiated thyroid cancer
Pastor, Susana (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Akdi, Abdelmounaim (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
González, Eddy R. (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Castell-Conesa, Joan (Hospital Universitari Vall d'Hebron)
Biarnés, Josefina (Hospital Universitari de Girona Doctor Josep Trueta)
Marcos Dauder, Ricardo (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
Velázquez, Antonia (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date:	2012
Abstract:	Thyroid hormone receptors, THRA and THRB, together with the TSH receptor, TSHR, are key regulators of thyroid function. Alterations in the genes of these receptors (THRA, THRB and TSHR) have been related to thyroid diseases, including thyroid cancer. Moreover, there is evidence suggesting that predisposition to differentiated thyroid cancer (DTC) is related to common genetic variants with low penetrance that interact with each other and with environmental factors. In this study, we investigated the association of single nucleotide polymorphisms (SNPs) in the THRA (one SNP), THRB (three SNPs) and TSHR (two SNPs) genes with DTC risk. A case-control association study was conducted with 398 patients with sporadic DTC and 479 healthy controls from a Spanish population. Among the polymorphisms studied, only THRA -rs939348 was found to be associated with an increased risk of DTC (recessive model, odds ratio=1. 80, 95% confidence interval=1. 03-3. 14, P =0. 037). Gene-gene interaction analysis using the genotype data of this study together with our previous genotype data on TG and TRHR indicated a combined effect of the pairwises: THRB - TG (P =0. 014, THRB -rs3752874 with TG -rs2076740; P =0. 099, THRB -rs844107 with TG -rs2076740) and THRB - TRHR (P =0. 0024, THRB -rs3752874 with TRHR -rs4129682) for DTC risk in a Spanish population. Our results confirm that THRA is a risk factor for DTC, and we show for the first time the combined effect of THRB and TG or TRHR on DTC susceptibility, supporting the importance of gene-gene interaction in thyroid cancer risk.
Grants:	Ministerio de Educación y Ciencia SAF2007-6338 Agència de Gestió d'Ajuts Universitaris i de Recerca 2009-SGR-725
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Thyroid-function genes ; Association ; Thyroid cancer risk ; Cancer susceptibility
Published in:	Endocrine Connections, Vol. 1, Núm. 1 (august 2012) , p. 68-77, ISSN 2049-3614

DOI: 10.1530/EC-12-0017
PMID: 23781307

10 p, 208.5 KB

The record appears in these collections:
Articles > Research articles
Articles > Published articles