Background
Familial nonmedullary thyroid cancer (FNMTC) is associated with earlier onset and
more aggressive behavior than its sporadic counterpart. Although candidate chromosomal
loci have been proposed for isolated families with variants of FNMTC, the etiology
of most cases is unknown. We aimed to identify loci linked to FNMTC susceptibility
using single-nucleotide polymorphism (SNP) array-based linkage analysis in a broad
sampling of affected families.
Methods
We enrolled and pedigreed 38 FNMTC families. Genomic DNA was extracted from the peripheral
blood of 110 relatives, and hybridized to Affymetrix SNP arrays. We performed genotyping
and linkage analysis, calculating exponential logarithm-of-the-odds (LOD) scores to
identify chromosomal loci with a significant likelihood of linkage.
Results
Forty-nine affected and 61 unaffected members of FNMTC families were genotyped. In
pooled linkage analysis of all families, 2 distinct loci with significant linkage
were detected at 6q22 and 1q21 (LOD=3.3 and 3.04, respectively).
Conclusion
We have identified 2 loci on chromosomes 1 and 6 that demonstrate linkage in a broad sampling
of FNMTC families. Our findings suggest the presence of germline mutations in heretofore-undiscovered
genes at these loci, which may potentially lead to accurate genetic tests. Future studies
will consist of technical validation and subset analyses of higher-risk pedigrees.
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Article info
Publication history
Accepted:
September 17,
2009
Footnotes
Supported by Helen and Sanford Diller Foundation, Heller Family Foundation, Grove Foundation, Friends of Endocrine Surgery.
Identification
Copyright
© 2009 Mosby, Inc. Published by Elsevier Inc. All rights reserved.
