FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility.
Clin Endocrinol (Oxf)
; 77(6): 926-33, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22882326
ABSTRACT
OBJECTIVE:
FOXE1 is a transcription factor required for thyroid differentiation and function. FOXE1 locus polymorphisms (chromosome 9q22.33) were recently associated with increased sporadic thyroid cancer risk. In this study, we aimed to investigate the association of FOXE1 variants with nonmedullary thyroid cancer (NMTC), in both sporadic and familial (FNMTC) cases from the Portuguese population. DESIGN ANDMETHODS:
Nine variants located at the FOXE1 locus were sequenced in genomic DNA from 60 FNMTC probands and 80 patients with sporadic NMTC. Alleles were tested for association with thyroid cancer, against 130 healthy matched Portuguese controls.RESULTS:
All variants were significantly associated with increased thyroid cancer risk when combining familial and sporadic cases (OR range = 1·62-2·58). In particular, two reported risk variants were associated with the disease rs965513 (allele A) with familial (OR = 2·30, 95% CI = 1·48-3·59, P = 0·0002) and sporadic (OR = 2·81, 95% CI = 1·87-4·22, P < 0·0001) NMTC and rs1867277 (allele A) with the sporadic (OR = 1·76, 95% CI = 1·18-2·62, P = 0·0052) and combined NMTC cases (OR = 1·70, 95% CI = 1·21-2·40, P = 0·0022). Interestingly, we also identified association of FOXE1 polyalanine tract expansions (>14 alanines) with thyroid cancer risk, in both familial (OR = 2·56, 95% CI = 1·64-4·01, P < 0·0001) and sporadic (OR = 2·44, 95% CI = 1·61-3·68, P < 0·0001) cases.CONCLUSIONS:
We found compelling evidence of association between FOXE1 variants and thyroid cancer risk in the Portuguese population. To our knowledge, this is the first study supporting the association of this locus with both sporadic and familial NMTC susceptibility.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Neoplasias de la Tiroides
/
Predisposición Genética a la Enfermedad
/
Factores de Transcripción Forkhead
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Aged80
/
Humans
/
Middle aged
País/Región como asunto:
Europa
Idioma:
En
Revista:
Clin Endocrinol (Oxf)
Año:
2012
Tipo del documento:
Article
País de afiliación:
Portugal