Genome-wide association and expression quantitative trait loci studies identify multiple susceptibility loci for thyroid cancer

Nat Commun. 2017 Jul 13;8:15966. doi: 10.1038/ncomms15966.


Thyroid cancer is the most common cancer in Korea. Several susceptibility loci of differentiated thyroid cancer (DTC) were identified by previous genome-wide association studies (GWASs) in Europeans only. Here we conducted a GWAS and a replication study in Koreans using a total of 1,085 DTC cases and 8,884 controls, and validated these results using expression quantitative trait loci (eQTL) analysis and clinical phenotypes. The most robust associations were observed in the NRG1 gene (rs6996585, P=1.08 × 10-10) and this SNP was also associated with NRG1 expression in thyroid tissues. In addition, we confirmed three previously reported loci (FOXE1, NKX2-1 and DIRC3) and identified seven novel susceptibility loci (VAV3, PCNXL2, INSR, MRSB3, FHIT, SEPT11 and SLC24A6) associated with DTC. Furthermore, we identified specific variants of DTC that have different effects according to cancer type or ethnicity. Our findings provide deeper insight into the genetic contribution to thyroid cancer in different populations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Female
  • Forkhead Transcription Factors / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Proteins / genetics
  • Polymorphism, Single Nucleotide
  • Proto-Oncogene Proteins c-vav / genetics
  • Quantitative Trait Loci*
  • Thyroid Neoplasms / genetics*
  • Thyroid Nuclear Factor 1 / genetics


  • FOXE1 protein, human
  • Forkhead Transcription Factors
  • NKX2-1 protein, human
  • Neoplasm Proteins
  • PCNX2 protein, human
  • Proto-Oncogene Proteins c-vav
  • Thyroid Nuclear Factor 1
  • VAV3 protein, human