Familial nontoxic multinodular thyroid goiter locus maps to chromosome 14q but does not account for familial nonmedullary thyroid cancer.
Thyroid goiter is a common condition that is often associated with iodine deficiency. Familial forms of goiter in areas not known to feature iodine deficiency are much less common. We have performed a genomic search on a single large Canadian family with 18 cases of nontoxic multinodular goiter in which 2 individuals also had papillary lesions highly suggestive of papillary carcinoma. A locus on chromosome 14q (MNG1 [multinodular goiter 1]) has been identified, with a maximal two-point LOD score of 3.8 at D14S1030 and a multipoint LOD score of 4.88 at the same marker, defined by D14S1062 (upper boundary) and D14S267 (lower boundary). The gene encoding thyroid-stimulating hormone receptor (TSHR), which is located on chromosome 14q, is outside the linked region. To determine the role of this gene in familial nonmedullary thyroid cancer (NMTC), we studied 37 smaller pedigrees each containing at least two cases of NMTC. Analysis by both parametric and nonparametric methods indicates that only a very small proportion of familial NMTC (point estimate 0.001, support intervals 0-.6 under a dominant model) is attributable to MNG1.
Bignell
G R
GR
Section of Molecular Carcinogeneis, Institute of Cancer Research, Sutton, Surrey.
Canzian
F
F
Shayeghi
M
M
Stark
M
M
Shugart
Y Y
YY
Biggs
P
P
Mangion
J
J
Hamoudi
R
R
Rosenblatt
J
J
Buu
P
P
Sun
S
S
Stoffer
S S
SS
Goldgar
D E
DE
Romeo
G
G
Houlston
R S
RS
Narod
S A
SA
Stratton
M R
MR
Foulkes
W D
WD
D002170:Canada; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D005819:Genetic Markers; D006044:Goiter, Nodular / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008126:Lod Score; D008297:Male; D010375:Pedigree; D011989:Receptors, Thyrotropin / Q000235:genetics; D013964:Thyroid Neoplasms / Q000209:etiology / Q000235:genetics*
D005819:Genetic Markers; D011989:Receptors, Thyrotropin