FOXE1 association with differentiated thyroid cancer and its progression

Thyroid. 2014 May;24(5):845-51. doi: 10.1089/thy.2013.0274. Epub 2014 Jan 29.


Background: Single nucleotide polymorphisms (SNPs) near thyroid transcription factor genes (FOXE1 rs965513/NKX2-1 rs944289) have been shown to be associated with differentiated thyroid cancer (DTC) in Caucasoid populations. We investigated the role of those SNPs in German patients with DTC and also extended our analysis to tumor stages and lymphocytic infiltration of the tumors (ITL).

Methods: Patients with DTC (n=243; papillary, PTC; follicular, FTC) and healthy controls (HC; n=270) were analyzed for the rs965513 and rs944289 SNPs.

Results: The case-control analysis for rs965513 SNP showed that the genotypes "AA," "AG," and minor allele "A" were more frequent in patients with DTC than in HC (pronounced in PTC p(genotype)=0.000084, p(allele)=0.006 than FTC p(genotype)=0.29 and p(allele)=0.06). Furthermore, subgroup analysis of the DTC patients stratified for primary tumor stage (T1-T2, T3-T4), the absence or presence of regional lymph node metastases (N0, N1), for distant metastases (M0, M1), as well as for ITL, showed an association of rs965513 with stages T1-T2, T1-T3, N1, and absence of ITL. The NKX2-1 SNP rs944289, however, was not associated with DTC.

Conclusion: Our results confirm that the FOXE1 rs965513 SNP confers an increased risk for DTC in the German population, particularly allele "A" and the genotypes "AA" and "AG" for PTC. This increased risk was also observed in advanced tumor stages and absence of ITL, which may reflect the course of a more aggressive disease. The NKX2-1 rs944289 SNP, however, appears to play a secondary role in the development of DTC in the German population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular / genetics
  • Adenocarcinoma, Follicular / immunology
  • Adenocarcinoma, Follicular / pathology
  • Adenocarcinoma, Follicular / secondary
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma / genetics
  • Carcinoma / immunology
  • Carcinoma / pathology
  • Carcinoma / secondary
  • Carcinoma, Papillary
  • Case-Control Studies
  • Cell Transformation, Neoplastic
  • Female
  • Forkhead Transcription Factors / genetics*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Germany
  • Hospitals, University
  • Humans
  • Lymphatic Metastasis
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Polymorphism, Single Nucleotide*
  • Thyroid Cancer, Papillary
  • Thyroid Gland / immunology
  • Thyroid Gland / pathology
  • Thyroid Neoplasms / genetics*
  • Thyroid Neoplasms / immunology
  • Thyroid Neoplasms / pathology
  • Thyroid Neoplasms / secondary
  • Young Adult


  • FOXE1 protein, human
  • Forkhead Transcription Factors

Supplementary concepts

  • Thyroid cancer, follicular