title: The HABP2 G534E variant is an unlikely cause of familial non-medullary thyroid cancer.
abstract: A recent study reported the non-synonymous G534E (rs7080536, allele A) variant in the HABP2 gene as causal in familial non-medullary thyroid cancer (NMTC).
  
  
  
  The objective of this study was to evaluate the causality of HABP2 G534E in the TCUKIN study, a multi-center population based study of NMTC cases from the British Isles.
  
  
  
  A case-control analysis of rs7080536 genotypes was performed using 2,105 TCUKIN cases and 5,172 UK controls.
  
  
  
  Cases comprised 2,105 NMTC cases. Patients sub-groups with papillary (N=1,056), follicular (N=691) and Hurthle cell (N=86) TC cases were studied separately. Controls comprised 5,172 individuals from the 1958 Birth Cohort (58C) and the National Blood Donor Service (NBS) study. The controls had previously been genotyped using genome-wide SNP arrays by the Wellcome Trust Case Control Consortium study.
  
  
  
  Measures: Association between HABP2 G534E (rs7080536A) and NMTC risk was evaluated using logistic regression.
  
  
  
  The frequency of HABP2 G534E was 4.2% in cases and 4.6% in controls. We did not detect an association between this variant and NMTC risk (OR=0.896, 95% CI: 0.746-1.071, P=0.233). We also failed to detect an association between HABP2 G534E and cases with papillary (1056 cases, G534E frequency= 3.5%, OR=0.74, P=0.017), follicular (691 cases, G534E frequency= 4.7%, OR=1.00, P=1.000) or Hurthle cell (86 cases, G534E frequency= 6.3%, OR=1.40, P=0.279) histology.
  
  
  
  We found that HABP2 G534E is a low-to-moderate frequency variant in the British Isles and failed to detect an association with NMTC risk, independent of histological type. Hence, our study does not implicate HABP2 G534E or a correlated polymorphism in familial NMTC and additional data are required before using this variant in NMTC risk assessment.
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.
authors.forename: Ruta
authors.initials: R
authors.lastname: Sahasrabudhe
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.
authors.forename: Jacob
authors.initials: J
authors.lastname: Stultz
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.
authors.forename: John
authors.initials: J
authors.lastname: Williamson
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Lott
authors.affiliation: Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.
authors.forename: Ana
authors.initials: A
authors.lastname: Estrada
authors.affiliation: Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.
authors.forename: Mabel
authors.initials: M
authors.lastname: Bohorquez
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Claire
authors.initials: C
authors.lastname: Palles
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.|Fundación de Genómica y Genética Molecular, Colombia.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Polanco-Echeverry
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Emma
authors.initials: E
authors.lastname: Jaeger
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Lynn
authors.initials: L
authors.lastname: Martin
authors.affiliation: Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.
authors.forename: Maria
authors.initials: M
authors.lastname: Magdalena Echeverry
authors.affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom.
authors.forename: Ian
authors.initials: I
authors.lastname: Tomlinson
authors.affiliation: Genome Center and Department of Biochemistry and Molecular Medicine, School of Medicine, University of California, Davis, USA.|Grupo de Citogenética, Filogenia y Evolución de Poblaciones, Facultades de Ciencias y Facultad de Ciencias de la Salud, Universidad del Tolima, Ibagué, Colombia.|Fundación de Genómica y Genética Molecular, Colombia.
authors.forename: Luis G
authors.initials: LG
authors.lastname: Carvajal-Carmona