FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility

• Type: Article in International Scientific Journal
• Date: 2012

Authors

Tomaz, RA (Author) Other; Sousa, I (Author) Other; Silva, JG (Author) Other; Santos, C (Author) Other; Manuel R Teixeira (Author) ICBAS; Leite, V (Author) Other; Cavaco, BM (Author) Other

Journal

Title: Clinical Endocrinology

Vol. 77

Pages: 926-933

ISSN: 0300-0664

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 43 Citations

Scopus - 50 Citations

Other information

Authenticus ID: P-002-2KC

DOI: 10.1111/j.1365-2265.2012.04505.x

Abstract (EN): 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 and Methods 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 = 1.622.58). In particular, two reported risk variants were associated with the disease: rs965513 (allele A) with familial (OR = 2.30, 95% CI = 1.483.59, P = 0.0002) and sporadic (OR = 2.81, 95% CI = 1.874.22, P < 0.0001) NMTC and rs1867277 (allele A) with the sporadic (OR = 1.76, 95% CI = 1.182.62, P = 0.0052) and combined NMTC cases (OR = 1.70, 95% CI = 1.212.40, 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 = 1.644.01, P < 0.0001) and sporadic (OR = 2.44, 95% CI = 1.613.68, 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8