title: Association of FOXE1 polyalanine repeat region with thyroid cancer is dependent on tumour size.
abstract: OBJECTIVE
  Polymorphisms in the thyroid transcription factor forkhead factor E1 (FOXE1) gene have been implicated in the genetic susceptibility to differentiated thyroid cancer, but little is known about their effect on tumour characteristics. The objective of this study was to determine the contribution of the FOXE1 polyalanine repeat region to the susceptibility to thyroid cancer and to its clinical characteristics.
  
  
  METHODS
  A total of 500 patients with sporadic thyroid cancer (440 papillary and 60 follicular thyroid carcinoma) and 502 healthy controls were included in this case-control association study. The number of FOXE1 alanine repeats in each subject was determined by PCR and multiplex fragment analysis by capillary electrophoresis. FOXE1 genotype and allele frequencies among groups were compared by logistic regression and adjusted for sex and age at diagnosis. Data were analysed according to cancer subtype, tumour size and the presence of lymph node or distant metastasis.
  
  
  RESULTS
  FOXE1 alleles with 16 or more alanine repeats were more frequent in patients with tumour size > 1 cm compared to tumour size ≤ 1 cm (adjusted OR 1·44; 95% CI 1·05-1·88; P = 0·019). Genotypes containing at least one allele with 16 or more alanine repeats were associated with larger tumour size (adjusted OR 1·71; 95% CI 1·15-2·57; P = 0·009). No significant differences were observed between cancer subtypes or the presence/absence of metastasis.
  
  
  CONCLUSIONS
  FOXE1 polyalanine repeat polymorphisms are associated with thyroid cancer, but only for tumours larger than 1 cm, suggesting a role in disease progression.
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Joana
authors.initials: J
authors.lastname: Raimundo
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Maria I
authors.initials: MI
authors.lastname: Alvelos
authors.affiliation: Endocrinology Service, Portuguese Institute of Oncology of Coimbra, Coimbra, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Azevedo
authors.affiliation: Endocrinology Service, Portuguese Institute of Oncology of Coimbra, Coimbra, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Martins
authors.affiliation: Endocrinology Service, Portuguese Institute of Oncology of Coimbra, Coimbra, Portugal.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Rodrigues
authors.affiliation: CICS-UBI, Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
authors.forename: Manuel C
authors.initials: MC
authors.lastname: Lemos
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D018450:Disease Progression; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides; D012091:Repetitive Sequences, Nucleic Acid; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology; D047368:Tumor Burden / Q000235:genetics
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D010455:Peptides; C019529:polyalanine