title: The common genetic variant rs944289 on chromosome 14q13.3 associates with risk of both malignant and benign thyroid tumors in the Japanese population.
abstract: BACKGROUND
  Several single nucleotide polymorphisms (SNP) have been identified to be associated with the risk for differentiated thyroid cancer in populations of distinct ethnic background. The relationship of these genetic markers to a benign tumor of the thyroid, follicular adenoma (FA), is not well established.
  
  
  METHODS
  In a multicenter retrospective case-control study, five thyroid cancer-related SNPs-rs966513 (9q22.33, FOXE1), rs944289 (14q13.3, PTCSC3), rs2439302 (8p12, NRG1), rs1867277 (9q22.23, FOXE1), and rs6983267 (8q24, POU5F1B)-were genotyped in 959 cases of histologically verified FA, 535 papillary thyroid carcinomas (PTC), and 2766 population controls.
  
  
  RESULTS
  A significant association was found between FA and rs944289 (p=0.002; OR 1.176 [CI 1.064-1.316]), and suggestively with rs2439302 (p=0.033; OR 1.149 [CI 1.010-1.315]). In PTC, significant associations were confirmed for rs965513 (p=4.21E-04; OR 1.587 [CI 1.235-2.000]) and rs944289 (p=0.003; OR 1.234 [CI 1.075-1.408]), newly found for rs2439302 (p=0.003; OR 1.266 [CI 1.087-1.493]) and rs1867277 (p=1.17E-04; OR 1.492 [CI 1.235-1.818]), and was not replicated for rs6983267 (p=0.082; OR 1.136 [CI 0.980-1.316]) in this series. A significant correlation between rs2439302 genotype and relative expression of NRG1 was detected in normal and tumor counterparts of PTC (about 10% decrease per each risk allele). NRG1 expression also significantly correlated with that of PTCSC3.
  
  
  CONCLUSIONS
  Association of rs944289, which was previously known to confer risk for thyroid cancer, with FA, and the correlation between PTCSC3 and NRG1 expression demonstrates that predisposing genetic factors are partly common for benign and malignant thyroid tumors, and imply broader roles of the pathways they underlie in thyroid tumorigenesis, not limited to carcinogenesis.
authors.affiliation: 1 Department of Global Health, Medicine, and Welfare, Nagasaki University , Nagasaki, Japan .
authors.forename: Tatiana I
authors.initials: TI
authors.lastname: Rogounovitch
authors.forename: Andrey
authors.initials: A
authors.lastname: Bychkov
authors.forename: Meiko
authors.initials: M
authors.lastname: Takahashi
authors.forename: Norisato
authors.initials: N
authors.lastname: Mitsutake
authors.forename: Masahiro
authors.initials: M
authors.lastname: Nakashima
authors.forename: Alyaksandr V
authors.initials: AV
authors.lastname: Nikitski
authors.forename: Tomayoshi
authors.initials: T
authors.lastname: Hayashi
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Hirokawa
authors.forename: Katsu
authors.initials: K
authors.lastname: Ishigaki
authors.forename: Kazuto
authors.initials: K
authors.lastname: Shigematsu
authors.forename: Tetiana
authors.initials: T
authors.lastname: Bogdanova
authors.forename: Michiko
authors.initials: M
authors.lastname: Matsuse
authors.forename: Eijun
authors.initials: E
authors.lastname: Nishihara
authors.forename: Shigeki
authors.initials: S
authors.lastname: Minami
authors.forename: Kosho
authors.initials: K
authors.lastname: Yamanouchi
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ito
authors.forename: Takahisa
authors.initials: T
authors.lastname: Kawaguchi
authors.forename: Hisayoshi
authors.initials: H
authors.lastname: Kondo
authors.forename: Noboru
authors.initials: N
authors.lastname: Takamura
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ito
authors.forename: Akira
authors.initials: A
authors.lastname: Miyauchi
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Shunichi
authors.initials: S
authors.lastname: Yamashita
authors.forename: Vladimir A
authors.initials: VA
authors.lastname: Saenko
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D002874:Chromosome Mapping; D002875:Chromosomes / Q000648:ultrastructure; D015331:Cohort Studies; D005260:Female; D005786:Gene Expression Regulation; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D020890:Neuregulin-1 / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors; D017422:Sequence Analysis, DNA; D013964:Thyroid Neoplasms / Q000235:genetics*; D055815:Young Adult
chemical_list: C094131:NRG1 protein, human; D020890:Neuregulin-1; C000603517:Ptcsc3 untranslated RNA, human; D022661:RNA, Untranslated