title: The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid carcinoma in the Japanese population.
abstract: BACKGROUND
  FOXE1 and NKX2-1 are two known genetic risk factors for the predisposition to sporadic papillary thyroid carcinoma (PTC) in Europeans, but their association in other ethnicities is still unknown.
  
  
  OBJECTIVE
  We aim to examine the association of the two genes with Japanese sporadic PTC, which exhibits high BRAF(V600E) mutation rate.
  
  
  METHODS
  507 Japanese sporadic PTC cases and 2766 controls were genotyped for rs965513 (FOXE1) and rs944289 (NKX2-1). PTC cases were also examined for their BRAF(V600E) mutational status.
  
  
  RESULTS
  The association of both rs965513 (p=1.27×10(-4), OR=1.69, 95% CI 1.29 to 2.21) and rs944289 (p=0.0121, OR=1.21, 95% CI 1.04 to 1.39) with the risk of sporadic PTC was confirmed. Subgroup analysis based on the BRAF mutational status showed strong association of rs965513 with BRAF(V600E)-positive cases (p=2.26×10(-4), OR=1.72, 95% CI 1.29 to 2.29), but not with BRAF(V600E)-negative cases (p=0.143, OR=1.52, 95% CI 0.87 to 2.65). However, there was no difference in the observed effect size between both subgroups. For rs944289, both subgroups showed marginal association (p=0.0585, OR=1.17, 95% CI 0.99 to 1.37 for BRAF(V600E)-positive cases; p=0.0492, OR=1.35, 95% CI 1.00 to 1.81 for BRAF(V600E)-negative cases).
  
  
  CONCLUSIONS
  Both FOXE1 and NKX2-1 were associated with the increased risk of sporadic Japanese PTC. No clear associations were observed for either SNP with BRAF(V600E) status.
authors: Department of Molecular Medicine, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors: Michiko
authors: M
authors: Matsuse
authors: Meiko
authors: M
authors: Takahashi
authors: Norisato
authors: N
authors: Mitsutake
authors: Eijun
authors: E
authors: Nishihara
authors: Mitsuyoshi
authors: M
authors: Hirokawa
authors: Takahisa
authors: T
authors: Kawaguchi
authors: Tatiana
authors: T
authors: Rogounovitch
authors: Vladimir
authors: V
authors: Saenko
authors: Andrey
authors: A
authors: Bychkov
authors: Keiji
authors: K
authors: Suzuki
authors: Keitaro
authors: K
authors: Matsuo
authors: Kazuo
authors: K
authors: Tajima
authors: Akira
authors: A
authors: Miyauchi
authors: Ryo
authors: R
authors: Yamada
authors: Fumihiko
authors: F
authors: Matsuda
authors: Shunichi
authors: S
authors: Yamashita
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044466:Asian People; D002277:Carcinoma; D002291:Carcinoma, Papillary / Q000208:ethnology / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000208:ethnology / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D029961:Zebrafish Proteins
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D000090322:Homeobox Protein Nkx-2.2; D018398:Homeodomain Proteins; D014157:Transcription Factors; D029961:Zebrafish Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf