Objective: FOXE1 is an intronless gene on chromosome 9 which plays a significant role in thyroid morphogenesis. Mutations in FOXE1 are associated with thyroid phenotypes including congenital hypothyroidism, thyroid dysgenesis and thyroid cancer. This study aims to investigate the frequency and impact of a single nucleotide polymorphism(rs965513, G>A) at 9q22.23 in a Western European cohort of patients with differentiated thyroid cancer(DTC), compared to controls.
Design: This is a candidate gene case control study.
Methods: 277 patients with histologically confirmed DTC were recruited from tertiary referral centres in Ireland and France. 309 cancer-free controls were recruited from the community. DNA was extracted from buccal swabs or whole blood of control subjects and patients with DTC. Allelic and genotypic frequencies among patients were compared with controls, to assess the risk for disease conferred by homozygous and heterozygous carriers compared to wild-type genotypes. Genotyping was performed using Taqman-based PCR.
Results: 277 patients with confirmed DTC and 309 non-cancer controls were genotyped. The frequency of the minor allele among cases was 0.45 compared to 0.34 among controls. The genotypic odds ratio for heterozygotes was 1.66(CI 1.16-2.39, p=0.00555), increasing to 2.93(CI 1.70-5.05, p=0.00007) for rare homozygotes. All subjects were in Hardy-Weinberg equilibrium(X2, p=0.09, p=0.07 respectively).
Conclusions: This FOXE1 polymorphism is a low penetrance variant associated with DTC susceptibility in this cohort. The minor allele was identified among patients with thyroid cancer significantly more frequently than controls. An allele dosage effect was observed, with rare homozygous genotypes conferring greater risk than heterozygotes.