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Thyroid cancer GWAS identifies 10q26.12 and 6q14.1 as novel susceptibility loci and reveals genetic heterogeneity among populations
Author(s) -
Mancikova Veronika,
Cruz Raquel,
IngladaPérez Lucía,
FernándezRozadilla Ceres,
Landa Iñigo,
CameselleTeijeiro José,
Celeiro Catuxa,
Pastor Susana,
Velázquez Antonia,
Marcos Ricard,
Andía Victor,
ÁlvarezEscolá Cristina,
Meoro Amparo,
Schiavi Francesca,
Opocher Giuseppe,
Quintela Inés,
AnsedeBermejo Juan,
RuizPonte Clara,
Santisteban Pilar,
Robledo Mercedes,
Carracedo Angel
Publication year - 2015
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.29557
Subject(s) - genome wide association study , biology , genetics , single nucleotide polymorphism , genetic association , allele , thyroid cancer , genetic architecture , genetic predisposition , heritability , locus (genetics) , genetic variation , disease , genotype , cancer , quantitative trait locus , gene , medicine
Thyroid cancer is the most heritable cancer of all those not displaying typical Mendelian inheritance. However, most of the genetic factors that would explain the high heritability remain unknown. Our aim was to identify additional common genetic variants associated with susceptibility to this disease. In order to do so, we performed a genome‐wide association study in a series of 398 cases and 502 controls from Spain, followed by a replication in four well‐defined Southern European case‐control collections contributing a total of 1,422 cases and 1,908 controls. The association between the variation at the 9q22 locus near FOXE1 and thyroid cancer risk was consistent across all series, with several SNPs identified (rs7028661: OR = 1.64, p = 1.0 × 10 −22 , rs7037324: OR = 1.54, p = 1.2 × 10 −17 ). Moreover, the rare alleles of three SNPs (rs2997312, rs10788123 and rs1254167) at 10q26.12 showed suggestive evidence of association with higher risk of the disease (OR = 1.35, p = 1.2 × 10 −04 , OR = 1.26, p = 5.2 × 10 −04 and OR = 1.38, p = 5.9 × 10 −05 , respectively). Finally, the rare allele of rs4075570 at 6q14.1 conferred protection in the series studied (OR = 0.82, p = 2.0 × 10 −04 ). This study suggests that heterogeneity in genetic susceptibility between populations is a key feature to take into account when exploring genetic risk factors related to this disease.