The FOXE1 rs965513 polymorphism: a pleiotropic risk locus associated with thyroid function, BRAFV600E mutation, and susceptibility to papillary thyroid cancer

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.