title: FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility.
abstract: OBJECTIVE
  FOXE1 is a transcription factor required for thyroid differentiation and function. FOXE1 locus polymorphisms (chromosome 9q22.33) were recently associated with increased sporadic thyroid cancer risk. In this study, we aimed to investigate the association of FOXE1 variants with nonmedullary thyroid cancer (NMTC), in both sporadic and familial (FNMTC) cases from the Portuguese population.
  
  
  METHODS
  Nine variants located at the FOXE1 locus were sequenced in genomic DNA from 60 FNMTC probands and 80 patients with sporadic NMTC. Alleles were tested for association with thyroid cancer, against 130 healthy matched Portuguese controls.
  
  
  RESULTS
  All variants were significantly associated with increased thyroid cancer risk when combining familial and sporadic cases (OR range = 1·62-2·58). In particular, two reported risk variants were associated with the disease: rs965513 (allele A) with familial (OR = 2·30, 95% CI = 1·48-3·59, P = 0·0002) and sporadic (OR = 2·81, 95% CI = 1·87-4·22, P < 0·0001) NMTC and rs1867277 (allele A) with the sporadic (OR = 1·76, 95% CI = 1·18-2·62, P = 0·0052) and combined NMTC cases (OR = 1·70, 95% CI = 1·21-2·40, P = 0·0022). Interestingly, we also identified association of FOXE1 polyalanine tract expansions (>14 alanines) with thyroid cancer risk, in both familial (OR = 2·56, 95% CI = 1·64-4·01, P < 0·0001) and sporadic (OR = 2·44, 95% CI = 1·61-3·68, P < 0·0001) cases.
  
  
  CONCLUSIONS
  We found compelling evidence of association between FOXE1 variants and thyroid cancer risk in the Portuguese population. To our knowledge, this is the first study supporting the association of this locus with both sporadic and familial NMTC susceptibility.
authors.affiliation: Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal.
authors.forename: Rute A
authors.initials: RA
authors.lastname: Tomaz
authors.forename: Inês
authors.initials: I
authors.lastname: Sousa
authors.forename: Joana G
authors.initials: JG
authors.lastname: Silva
authors.forename: Catarina
authors.initials: C
authors.lastname: Santos
authors.forename: Manuel R
authors.initials: MR
authors.lastname: Teixeira
authors.forename: Valeriano
authors.initials: V
authors.lastname: Leite
authors.forename: Branca M
authors.initials: BM
authors.lastname: Cavaco
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000453:epidemiology / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D051858:Forkhead Transcription Factors / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D015810:Linkage Disequilibrium; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors