Background FOXE1 and NKX2-1 are two known genetic risk factors for the predisposition to sporadic papillary thyroid carcinoma (PTC) in Europeans, but their association in other ethnicities is still unknown.

Objective We aim to examine the association of the two genes with Japanese sporadic PTC, which exhibits high BRAF^V600E mutation rate.

Methods 507 Japanese sporadic PTC cases and 2766 controls were genotyped for rs965513 (FOXE1) and rs944289 (NKX2-1). PTC cases were also examined for their BRAF^V600E mutational status.

Results The association of both rs965513 (p=1.27×10⁻⁴, OR=1.69, 95% CI 1.29 to 2.21) and rs944289 (p=0.0121, OR=1.21, 95% CI 1.04 to 1.39) with the risk of sporadic PTC was confirmed. Subgroup analysis based on the BRAF mutational status showed strong association of rs965513 with BRAF^V600E-positive cases (p=2.26×10⁻⁴, OR=1.72, 95% CI 1.29 to 2.29), but not with BRAF^V600E-negative cases (p=0.143, OR=1.52, 95% CI 0.87 to 2.65). However, there was no difference in the observed effect size between both subgroups. For rs944289, both subgroups showed marginal association (p=0.0585, OR=1.17, 95% CI 0.99 to 1.37 for BRAF^V600E-positive cases; p=0.0492, OR=1.35, 95% CI 1.00 to 1.81 for BRAF^V600E-negative cases).

Conclusions Both FOXE1 and NKX2-1 were associated with the increased risk of sporadic Japanese PTC. No clear associations were observed for either SNP with BRAF^V600E status.