The FOXE1 rs965513 polymorphism: a pleiotropic risk locus associated with thyroid function, BRAF(V600E) mutation, and susceptibility to papillary thyroid cancer

FOXE1 rs965513 多态性:一种与甲状腺功能、BRAF(V600E) 突变和乳头状甲状腺癌易感性相关的多效性风险位点

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Abstract

Although papillary thyroid cancer (PTC) genetic research has advanced from identifying driver genes to investigating susceptibility loci and gene-environment interactions, data in Chinese populations remain limited. A case-control study was conducted, enrolling 75 patients with PTC and 271 patients with benign thyroid nodules. After testing for Hardy-Weinberg equilibrium, the associations of the single nucleotide polymorphism (SNP) at the rs965513 locus with genetic susceptibility to PTC, risk of BRAF(V600E) mutation, and clinical parameters were analyzed using chi-square tests and multivariate logistic regression under multiple genetic models. Multi-genetic model analysis revealed that individuals carrying the A allele had a significantly increased risk of PTC compared with those with the GG genotype (aOR = 2.684, 95% CI: 1.395-5.164, P = 0.003). When stratified by BRAF(V600E) mutation status, the A allele was also associated with an increased risk of harboring the BRAF(V600E) mutation (aOR = 2.574, 95% CI: 1.202-5.512, P = 0.015). Additionally, the GG genotype was significantly associated with elevated thyroid-stimulating hormone (TSH) levels, whereas TSH levels were lower in A allele carriers. In summary, the A allele significantly elevates the risk of both PTC and BRAF(V600E) mutation, whereas the G allele acts protectively. The risk-conferring A allele demonstrated an inverse association with serum TSH levels.

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