A comprehensive meta-analysis of case-control association studies to evaluate polymorphisms associated with the risk of differentiated thyroid carcinoma

BACKGROUND: Linkage analyses and association studies suggested that inherited genetic variations play a role in the development of Differentiated Thyroid Carcinoma (DTC). METHODS: We combined the results from a Genome-Wide Association Study (GWAS) performed by our group and from published studies on DTC. With a first approach, we evaluated whether a SNP published as associated with the risk of DTC could replicate in our GWAS (using FDR as adjustment for multiple comparisons). With the second approach, meta-analyses were performed between literature and GWAS when both sources suggested an association, increasing the statistical power of the analysis. Moreover, the polygenic risk of the associated SNPs was calculated. RESULTS: rs1799814 (CYP1A1), rs1121980 (FTO), and 3 SNPs within 9q22 (rs965513, rs7048394, and rs894673) replicated the associations described in literature. In addition, the meta-analyses between literature and GWAS revealed ten more SNPs within 9q22, six within FTO, two within SOD1, and single variations within HUS1, WDR3, UGT2B7, ALOX12, TICAM1, ATG16L1, HDAC4, PIK3CA, SULF1, IL11RA, VEGFA, and 1p31.3, 2q35, 8p12, and 14q13. CONCLUSION: This analysis confirmed several published risk loci that could be involved in DTC predisposition. IMPACT: These findings provide evidence for the role of germline variants in DTC etiology and are consistent with a polygenic model of the disease.