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

Summary 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 = 1·62–2·58). 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 14 alanines) with thyroid cancer risk, in both familial (OR = 2·56, 95% CI = 1·64–4·01, P