title: Common genetic variants in pituitary-thyroid axis genes and the risk of differentiated thyroid cancer.
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 interaction=0.014, THRB-rs3752874 with TG-rs2076740; P interaction=0.099, THRB-rs844107 with TG-rs2076740) and THRB-TRHR (P interaction=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.
authors.affiliation: Grup de Mutagènesi, Departament de Genètica i de Microbiologia, Facultat de Biociències Universitat Autònoma de Barcelona 08193, Cerdanyola del Vallès Barcelona Spain ; CIBER Epidemiología y Salud Pública, ISCIII Barcelona Spain.
authors.forename: Susana
authors.initials: S
authors.lastname: Pastor
authors.forename: Abdelmounaim
authors.initials: A
authors.lastname: Akdi
authors.forename: Eddy R
authors.initials: ER
authors.lastname: González
authors.forename: Juan
authors.initials: J
authors.lastname: Castell
authors.forename: Josefina
authors.initials: J
authors.lastname: Biarnés
authors.forename: Ricard
authors.initials: R
authors.lastname: Marcos
authors.forename: Antonia
authors.initials: A
authors.lastname: Velázquez
keywords: association; cancer susceptibility; thyroid cancer risk; thyroid-function genes