RT Journal Article
SR Electronic
T1 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
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 158
OP 163
DO 10.1136/jmedgenet-2011-100586
VO 49
IS 3
A1 Jones, Angela M
A1 Howarth, Kimberley M
A1 Martin, Lynn
A1 Gorman, Maggie
A1 Mihai, Radu
A1 Moss, Laura
A1 Auton, Adam
A1 Lemon, Catherine
A1 Mehanna, Hisham
A1 Mohan, Hosahalli
A1 Clarke, Susan E M
A1 Wadsley, Jonathan
A1 Macias, Elena
A1 Coatesworth, Andrew
A1 Beasley, Matthew
A1 Roques, Tom
A1 Martin, Craig
A1 Ryan, Paul
A1 Gerrard, Georgina
A1 Power, Danielle
A1 Bremmer, Caroline
A1 ,
A1 Tomlinson, Ian
A1 Carvajal-Carmona, Luis G
YR 2012
UL http://jmg.bmj.com/content/49/3/158.abstract
AB 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).