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 - PubMed (original) (raw)
doi: 10.1136/jmedgenet-2011-100586. Epub 2012 Jan 25.
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 Power, Caroline Bremmer; TCUKIN Consortium; Ian Tomlinson, Luis G Carvajal-Carmona
Collaborators, Affiliations
- PMID: 22282540
- PMCID: PMC3286794
- DOI: 10.1136/jmedgenet-2011-100586
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 et al. J Med Genet. 2012 Mar.
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).
Conflict of interest statement
Competing interests: None.
References
- Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 2006;6:292–306 - PubMed
- Goldgar DE, Easton DF, Cannon-Albright LA, Skolnick MH. Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J Natl Cancer Inst 1994;86:1600–8 - PubMed
- Gudmundsson J, Sulem P, Gudbjartsson DF, Jonasson JG, Sigurdsson A, Bergthorsson JT, He H, Blondal T, Geller F, Jakobsdottir M, Magnusdottir DN, Matthiasdottir S, Stacey SN, Skarphedinsson OB, Helgadottir H, Li W, Nagy R, Aguillo E, Faure E, Prats E, Saez B, Martinez M, Eyjolfsson GI, Bjornsdottir US, Holm H, Kristjansson K, Frigge ML, Kristvinsson H, Gulcher JR, Jonsson T, Rafnar T, Hjartarsson H, Mayordomo JI, de la Chapelle A, Hrafnkelsson J, Thorsteinsdottir U, Kong A, Stefansson K. Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat Genet 2009;41:460–4 - PMC - PubMed
- Ruiz-Llorente S, Montero-Conde C, Milne RL, Moya CM, Cebrian A, Leton R, Cascon A, Mercadillo F, Landa I, Borrego S, Perez de Nanclares G, Alvarez-Escola C, Diaz-Perez JA, Carracedo A, Urioste M, Gonzalez-Neira A, Benitez J, Santisteban P, Dopazo J, Ponder BA, Robledo M. Association study of 69 genes in the ret pathway identifies low-penetrance loci in sporadic medullary thyroid carcinoma. Cancer Res 2007;67:9561–7 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Miscellaneous