Localization of a susceptibility gene for familial nonmedullary thyroid carcinoma to chromosome 2q21

Am J Hum Genet. 2001 Aug;69(2):440-6. doi: 10.1086/321979. Epub 2001 Jul 2.


The familial form of nonmedullary thyroid carcinoma (NMTC) is a complex genetic disorder characterized by multifocal neoplasia and a higher degree of aggressiveness than its sporadic counterpart. In a large Tasmanian pedigree (Tas1) with recurrence of papillary thyroid carcinoma (PTC), the most common form of NMTC, an extensive genomewide scan revealed a common haplotype on chromosome 2q21 in seven of the eight patients with PTC. To verify the significance of the 2q21 locus, we performed linkage analysis in an independent sample set of 80 pedigrees, yielding a multipoint heterogeneity LOD score (HLOD) of 3.07 (alpha=0.42), nonparametric linkage (NPL) 3.19, (P=.001) at marker D2S2271. Stratification based on the presence of at least one case of the follicular variant of PTC, the phenotype observed in the Tas1 family, identified 17 such pedigrees, yielding a maximal HLOD score of 4.17 (alpha=0.80) and NPL=4.99 (P=.00002) at markers AFMa272zg9 and D2S2271, respectively. These results indicate the existence of a susceptibility locus for familial NMTC on chromosome 2q21.

MeSH terms

  • Carcinoma, Papillary / epidemiology
  • Carcinoma, Papillary / genetics*
  • Chromosome Mapping*
  • Chromosomes, Human, Pair 2 / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease / genetics*
  • Goiter / epidemiology
  • Goiter / genetics
  • Haplotypes / genetics
  • Humans
  • Lod Score
  • Male
  • Models, Genetic
  • Molecular Sequence Data
  • Nuclear Proteins*
  • PAX8 Transcription Factor
  • Paired Box Transcription Factors
  • Pedigree
  • Phenotype
  • Prevalence
  • Statistics, Nonparametric
  • Tasmania / epidemiology
  • Thyroid Neoplasms / epidemiology
  • Thyroid Neoplasms / genetics*
  • Trans-Activators / genetics


  • DNA-Binding Proteins
  • Nuclear Proteins
  • PAX8 Transcription Factor
  • PAX8 protein, human
  • Paired Box Transcription Factors
  • Trans-Activators

Associated data

  • OMIM/138800
  • OMIM/188550
  • OMIM/603386
  • OMIM/605642