ArticlePLoS genetics2009
The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors.
Article in PLoS genetics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 13 of them syntheses that pooled it.
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Who cites it
87 citing papers in PubMed, 13 syntheses or guidelines pooled it, 163 citations in OpenAlex.
- Genetic drivers of etiologic heterogeneity in thyroid cancer.Nature communications · 2026Pooled it
- Exploration of the association between FOXE1 gene polymorphism and differentiated thyroid cancer: a meta-analysis.BMC medical genetics · 2018Pooled it
- Association Between X-Ray Cross-complementing Group 3 (XRCC3) Thr241Met Polymorphism and Risk of Thyroid Cancer: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015Pooled it
- TITF1 and TITF2 loci variants indicate significant associations with thyroid cancer.Endocrine · 2015Pooled it
- Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer.Medicine · 2015Pooled it
- Association between MTHFR C677T polymorphism and thyroid cancer risk: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Relationships of FOXE1 and ATM genetic polymorphisms with papillary thyroid carcinoma risk: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Common genetic variants on FOXE1 contributes to thyroid cancer susceptibility: evidence based on 16 studies.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Association between TP53 Arg72Pro polymorphism and thyroid carcinoma risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Significant associations between X-ray repair cross-complementing group 3 genetic polymorphisms and thyroid cancer risk.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Quantitative assessment of common genetic variants on FOXE1 and differentiated thyroid cancer risk.PloS one · 2014Pooled it
- A meta-analysis of thyroid-related traits reveals novel loci and gender-specific differences in the regulation of thyroid function.PLoS genetics · 2013Pooled it
- The insertion/deletion (I/D) polymorphism in the Angiotensin-converting enzyme gene and cancer risk: a meta-analysis.BMC medical genetics · 2011Pooled it
- Common single nucleotide polymorphisms in genes related to immune function and risk of papillary thyroid cancer.PloS one · 2013Trial
- The FOXE1 rs965513 polymorphism: a pleiotropic risk locus associated with thyroid function, BRAFScientific reports · 2026Article
- Identification of GermlineInternational journal of molecular sciences · 2024Article
- Chromosomal localization of mutated genes in non-syndromic familial thyroid cancer.Frontiers in oncology · 2024Review
- Reduced expression ofFrontiers in endocrinology · 2024Article
- Pathogenesis of cancers derived from thyroid follicular cells.Nature reviews. Cancer · 2023Review
- Foxe1 Deletion in the Adult Mouse Is Associated With Increased Thyroidal Mast Cells and Hypothyroidism.Endocrinology · 2022Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 19 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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 = 5.9x10(-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/alphaCREM 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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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.