TY - JOUR
T1 - RET polymorphisms and sporadic medullary thyroid carcinoma in a Portuguese population
AU - Sobrinho, Luís Adriano das Neves Gonçalves
AU - Bugalho, Maria João Guerreiro Martins
PY - 2005/1/1
Y1 - 2005/1/1
N2 - The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of RET proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S RET polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a RET germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p = 0.008) and found no significant associations for the other polymorphisms.
AB - The genetic basis of the sporadic form of medullary thyroid carcinoma, derived from "C" cells, is still poorly understood. Somatic mutations of RET proto-oncogene have been reported at a variable frequency ranging from 23% to 69%. The hypothesis that low penetrance factors, such as polymorphisms, might contribute to the phenotype of this neoplasm has been addressed in a few studies conducting to conflicting results. Herein, we studied 100 individuals (50 patients and 50 controls) aiming to compare the frequencies of G691S, L769L, S836S, and S904S RET polymorphisms observed in patients with respect to controls. Furthermore, meta-analysis of published studies including the present results was conducted. To test the contributory role of the above polymorphisms for the development of "C"-cell hyperplasia, we studied a group of 10 individuals selected for having a positive pentagastrin test despite the absence of a RET germline mutation. An over-representation of the G691S polymorphism, particularly in females, was observed in patients with respect to controls, although not reaching the level of significance. Allelic frequencies of the other three polymorphisms were not different in patients and controls. Results obtained in the admittedly small group of individuals with a positive pentagastrin test are unlikely to support a major influence of any polymorphism in the development of "C"-cell hyperplasia. The meta-analysis provided evidence for a significant association of the S691 allele with MTC (odds ratio 1.54, 95% confidence interval 1.12-2.12, p = 0.008) and found no significant associations for the other polymorphisms.
KW - meta-analysis
KW - cancer susceptibility
KW - MEN 2A
KW - SEQUENCE VARIANT
KW - PENTAGASTRIN STIMULATION TEST
KW - SOMATIC MUTATIONS
KW - RET
KW - MTC
KW - polymorphisms
KW - ENDOCRINE NEOPLASIA TYPE-2
KW - TYROSINE KINASE DOMAIN
KW - PROTOONCOGENE MUTATIONS
KW - HIRSCHSPRUNG-DISEASE
KW - PREDISPOSITION
KW - POINT MUTATION
U2 - 10.1385/ENDO:27:3:239
DO - 10.1385/ENDO:27:3:239
M3 - Article
C2 - 16230779
SN - 0969-711X
VL - 27
SP - 239
EP - 243
JO - Endocrine
JF - Endocrine
IS - 3
ER -