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Original article
Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24
  1. Angela M Jones1,
  2. Kimberley M Howarth1,
  3. Lynn Martin1,
  4. Maggie Gorman1,
  5. Radu Mihai2,
  6. Laura Moss3,
  7. Adam Auton1,
  8. Catherine Lemon4,
  9. Hisham Mehanna5,
  10. Hosahalli Mohan6,
  11. Susan E M Clarke6,
  12. Jonathan Wadsley7,
  13. Elena Macias8,
  14. Andrew Coatesworth9,
  15. Matthew Beasley10,
  16. Tom Roques11,
  17. Craig Martin11,
  18. Paul Ryan12,
  19. Georgina Gerrard13,
  20. Danielle Power14,
  21. Caroline Bremmer15,
  22. The TCUKIN Consortium*,
  23. Ian Tomlinson1,16,
  24. Luis G Carvajal-Carmona1
  1. 1Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  2. 2Department of Endocrine Surgery, John Radcliffe Hospital, Oxford, UK
  3. 3Velindre Cancer Centre, Cardiff, UK
  4. 4Mount Vernon Hospital, Northwood, UK
  5. 5Institute of Head and Neck Studies and Education, University Hospitals of Coventry and Warwickshire, Walsgrave, Coventry, UK
  6. 6Guys and St Thomas' NHS Foundation Trust and King's College London, London, UK
  7. 7Weston Park Hospital, Sheffield, UK
  8. 8Kent and Canterbury Hospital, Canterbury, UK
  9. 9York Hospital, York, UK
  10. 10Bristol Hematology and Oncology Centre, Bristol, UK
  11. 11Norfolk and Norwich University Hospital NHS Trust, Norwich, UK
  12. 12Medway Maritime Hospital, Gillingham, UK
  13. 13St. James University Hospital, Leeds, UK
  14. 14St Mary's Hospital, London, UK
  15. 15Newcross Hospital, Wolverhampton, UK
  16. 16NIHR Comprehensive Biomedical Research Centre, University of Oxford, Oxford, UK
  1. Correspondence to Dr Luis G Carvajal-Carmona, Wellcome Trust Centre for Human Genetics, Roosevelt Drive, Oxford OX3 7BN, UK; luis{at}


Five single nucleotide polymorphisms (SNPs) associated with thyroid cancer (TC) risk have been reported: rs2910164 (5q24); rs6983267 (8q24); rs965513 and rs1867277 (9q22); and rs944289 (14q13). Most of these associations have not been replicated in independent populations and the combined effects of the SNPs on risk have not been examined. This study genotyped the five TC SNPs in 781 patients recruited through the TCUKIN study. Genotype data from 6122 controls were obtained from the CORGI and Wellcome Trust Case-Control Consortium studies. Significant associations were detected between TC and rs965513A (p=6.35×10−34), rs1867277A (p=5.90×10−24), rs944289T (p=6.95×10−7), and rs6983267G (p=0.016). rs6983267 was most strongly associated under a recessive model (PGG vs GT + TT=0.004), in contrast to the association of this SNP with other cancer types. However, no evidence was found of an association between rs2910164 and disease under any risk model (p>0.7). The rs1867277 association remained significant (p=0.008) after accounting for genotypes at the nearby rs965513 (p=2.3×10−13) and these SNPs did not tag a single high risk haplotype. The four validated TC SNPs accounted for a relatively large proportion (∼11%) of the sibling relative risk of TC, principally owing to the large effect size of rs965513 (OR 1.74).

  • Thyroid cancer
  • genetic susceptibility
  • heritability
  • association study
  • candidate genes
  • cancer: gastric
  • genetics
  • cancer: colon
  • cancer: endocrine
  • complex traits
  • genetic epidemiology

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  • * A full list of the TCUKIN collaborators is listed in appendix 1.

  • Funding Cancer Research UK provided principal funding for this study. LGCC and IT receive funding from the FP7 CHIBCHA Consortium. The Wellcome Trust Centre for Human Genetics is funded by the Wellcome Trust (Grant number; 075491/Z/04).

  • Correction notice This paper has been corrected since it was first published online. The corresponding author's name should read Luis G Carvajal-Carmona.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval Ethics approval was provided by the Southampton and South West Hampshire Research Ethics Committee (A).

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement The data presented in the manuscript are available on request.