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

Angela M. Jones, Kimberley M. Howarth, Lynn Martin, Maggie Gorman, Radu Mihai, Laura Moss, Adam Auton, Catherine Lemon, Hisham Mehanna, Hosahalli Mohan, Susan E M Clarke, Jonathan Wadsley, Elena Macias, Andrew Coatesworth, Matthew Beasley, Tom Roques, Craig Martin, Paul Ryan, Georgina Gerrard, Danielle PowerCaroline Bremmer, Ian Tomlinson, Luis Carvajal-Carmona, Christopher Scrase, Andrew Goodman, James Gildersleve, Antony Robinson, Caroline Brammer, Hosahalli K. Mohan, Susan EM Clarke, Kate Goodchild, Abdel Hamid, Jerry Sharp, Mr Andrew Coatsworth, Hamish Courtney, Stephen Whitaker, Katie Wood, James McCaul, Christopher Ashford, Vivienne Loo, Jennifer Marshall, Amy Roy, Joanna Simpson, Nick Rowell, Mr Edward Babu, Narayanan Srihari, Mr Simon Ellenbogen, Arshad Jamil

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70 Scopus citations

Abstract

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 (P GG 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).

Original languageEnglish (US)
Pages (from-to)158-163
Number of pages6
JournalJournal of Medical Genetics
Volume49
Issue number3
DOIs
StatePublished - Mar 2012
Externally publishedYes

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Jones, A. M., Howarth, K. M., Martin, L., Gorman, M., Mihai, R., Moss, L., Auton, A., Lemon, C., Mehanna, H., Mohan, H., Clarke, S. E. M., Wadsley, J., Macias, E., Coatesworth, A., Beasley, M., Roques, T., Martin, C., Ryan, P., Gerrard, G., ... Jamil, A. (2012). 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. Journal of Medical Genetics, 49(3), 158-163. https://doi.org/10.1136/jmedgenet-2011-100586