In order to identify genetic factors related to thyroid cancer susceptibility, we adopted a candidate gene approach. We studied tag- and putative functional SNPs in genes involved in thyroid cell differentiation and proliferation, and in genes found to be differentially expressed in thyroid carcinoma. A total of 768 SNPs in 97 genes were genotyped in a Spanish series of 615 cases and 525 controls, the former comprising the largest collection of patients with this pathology from a single population studied to date. SNPs in an LD block spanning the entire FOXE1 gene showed the strongest evidence of association with papillary thyroid carcinoma susceptibility. This association was validated in a second stage of the study that included an independent Italian series of 482 patients and 532 controls. The strongest association results were observed for rs1867277 (OR[per-allele] = 1.49; 95%CI = 1.30–1.70; P = 5.9×10−9). Functional assays of rs1867277 (NM_004473.3:c.−283G>A) within the FOXE1 5′ UTR suggested that this variant affects FOXE1 transcription. DNA-binding assays demonstrated that, exclusively, the sequence containing the A allele recruited the USF1/USF2 transcription factors, while both alleles formed a complex in which DREAM/CREB/αCREM participated. Transfection studies showed an allele-dependent transcriptional regulation of FOXE1. We propose a FOXE1 regulation model dependent on the rs1867277 genotype, indicating that this SNP is a causal variant in thyroid cancer susceptibility. Our results constitute the first functional explanation for an association identified by a GWAS and thereby elucidate a mechanism of thyroid cancer susceptibility. They also attest to the efficacy of candidate gene approaches in the GWAS era.

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Diabetic neuropathy is defined as the presence of symptoms and signs of peripheral nerve dysfunction in diabetics. The aim of this study is to develop a predictive logistic model to identify the risk of losing protective sensitivity in the foot. This descriptive cross-sectional study included 111 patients diagnosed with diabetes mellitus. Participants completed a questionnaire designed to evaluate neuropathic symptoms, and multivariate analysis was subsequently performed to identify an optimal predictive model. The explanatory capacity was evaluated by calculating the R 2 coefficient of Nagelkerke. Predictive capacity was evaluated by calculating sensitivity, specificity, and estimation of the area under the receiver operational curve. Protective sensitivity loss was detected in 19.1% of participants. Variables associated by multivariate analysis were: educational level (OR: 31.4, 95% CI: 2.5-383.3, P = .007) and two items from the questionnaire: one related to bleeding and wet socks (OR: 28.3, 95% CI: 3.7-215.9, P = .001) and the other related to electrical sensations (OR: 52.9, 95% CI: 4.3-643.9, P = .002), which were both statistically significant. The predictive model included the variables of age, sex, duration of diabetes, and educational level, and it had a sensitivity of 81.3% and a specificity of 95.5%. This model has a high predictive capacity to identify patients at risk of developing sensory neuropathy.

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In comparing sporadic and MEN 2A phaeochromocytoma we found differences in age at presentation, mode of presentation, clinical data, duration of clinical features, imaging findings bilaterality and type of surgical treatment required.