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

Research output: Contribution to journalArticle

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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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Thyroid Neoplasms
Single Nucleotide Polymorphism
Chromosomes
Genotype
Haplotypes
Case-Control Studies
Siblings
Population
Neoplasms

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

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

In: Journal of Medical Genetics, Vol. 49, No. 3, 03.2012, p. 158-163.

Research output: Contribution to journalArticle

Jones, AM, Howarth, KM, Martin, L, Gorman, M, Mihai, R, Moss, L, Auton, A, Lemon, C, Mehanna, H, Mohan, H, Clarke, SEM, Wadsley, J, Macias, E, Coatesworth, A, Beasley, M, Roques, T, Martin, C, Ryan, P, Gerrard, G, Power, D, Bremmer, C, Tomlinson, I, Carvajal-Carmona, L, Scrase, C, Goodman, A, Gildersleve, J, Robinson, A, Brammer, C, Mohan, HK, Clarke, SEM, Goodchild, K, Hamid, A, Sharp, J, Coatsworth, MA, Courtney, H, Whitaker, S, Wood, K, McCaul, J, Ashford, C, Loo, V, Marshall, J, Roy, A, Simpson, J, Rowell, N, Babu, ME, Srihari, N, Ellenbogen, MS & 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, vol. 49, no. 3, pp. 158-163. https://doi.org/10.1136/jmedgenet-2011-100586
Jones, Angela M. ; Howarth, Kimberley M. ; Martin, Lynn ; Gorman, Maggie ; Mihai, Radu ; Moss, Laura ; Auton, Adam ; Lemon, Catherine ; Mehanna, Hisham ; Mohan, Hosahalli ; Clarke, Susan E M ; Wadsley, Jonathan ; Macias, Elena ; Coatesworth, Andrew ; Beasley, Matthew ; Roques, Tom ; Martin, Craig ; Ryan, Paul ; Gerrard, Georgina ; Power, Danielle ; Bremmer, Caroline ; Tomlinson, Ian ; Carvajal-Carmona, Luis ; Scrase, Christopher ; Goodman, Andrew ; Gildersleve, James ; Robinson, Antony ; Brammer, Caroline ; Mohan, Hosahalli K. ; Clarke, Susan EM ; Goodchild, Kate ; Hamid, Abdel ; Sharp, Jerry ; Coatsworth, Mr Andrew ; Courtney, Hamish ; Whitaker, Stephen ; Wood, Katie ; McCaul, James ; Ashford, Christopher ; Loo, Vivienne ; Marshall, Jennifer ; Roy, Amy ; Simpson, Joanna ; Rowell, Nick ; Babu, Mr Edward ; Srihari, Narayanan ; Ellenbogen, Mr Simon ; Jamil, Arshad. / 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. In: Journal of Medical Genetics. 2012 ; Vol. 49, No. 3. pp. 158-163.
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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).",
author = "Jones, {Angela M.} and Howarth, {Kimberley M.} and Lynn Martin and Maggie Gorman and Radu Mihai and Laura Moss and Adam Auton and Catherine Lemon and Hisham Mehanna and Hosahalli Mohan and Clarke, {Susan E M} and Jonathan Wadsley and Elena Macias and Andrew Coatesworth and Matthew Beasley and Tom Roques and Craig Martin and Paul Ryan and Georgina Gerrard and Danielle Power and Caroline Bremmer and Ian Tomlinson and Luis Carvajal-Carmona and Christopher Scrase and Andrew Goodman and James Gildersleve and Antony Robinson and Caroline Brammer and Mohan, {Hosahalli K.} and Clarke, {Susan EM} and Kate Goodchild and Abdel Hamid and Jerry Sharp and Coatsworth, {Mr Andrew} and Hamish Courtney and Stephen Whitaker and Katie Wood and James McCaul and Christopher Ashford and Vivienne Loo and Jennifer Marshall and Amy Roy and Joanna Simpson and Nick Rowell and Babu, {Mr Edward} and Narayanan Srihari and Ellenbogen, {Mr Simon} and Arshad Jamil",
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AU - Jones, Angela M.

AU - Howarth, Kimberley M.

AU - Martin, Lynn

AU - Gorman, Maggie

AU - Mihai, Radu

AU - Moss, Laura

AU - Auton, Adam

AU - Lemon, Catherine

AU - Mehanna, Hisham

AU - Mohan, Hosahalli

AU - Clarke, Susan E M

AU - Wadsley, Jonathan

AU - Macias, Elena

AU - Coatesworth, Andrew

AU - Beasley, Matthew

AU - Roques, Tom

AU - Martin, Craig

AU - Ryan, Paul

AU - Gerrard, Georgina

AU - Power, Danielle

AU - Bremmer, Caroline

AU - Tomlinson, Ian

AU - Carvajal-Carmona, Luis

AU - Scrase, Christopher

AU - Goodman, Andrew

AU - Gildersleve, James

AU - Robinson, Antony

AU - Brammer, Caroline

AU - Mohan, Hosahalli K.

AU - Clarke, Susan EM

AU - Goodchild, Kate

AU - Hamid, Abdel

AU - Sharp, Jerry

AU - Coatsworth, Mr Andrew

AU - Courtney, Hamish

AU - Whitaker, Stephen

AU - Wood, Katie

AU - McCaul, James

AU - Ashford, Christopher

AU - Loo, Vivienne

AU - Marshall, Jennifer

AU - Roy, Amy

AU - Simpson, Joanna

AU - Rowell, Nick

AU - Babu, Mr Edward

AU - Srihari, Narayanan

AU - Ellenbogen, Mr Simon

AU - Jamil, Arshad

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N2 - 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).

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