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.
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.
Authors: Jaroslaw Jendrzejewski; Andrew Thomas; Sandya Liyanarachchi; Andrew Eiterman; Jerneja Tomsic; Huiling He; Hanna S Radomska; Wei Li; Rebecca Nagy; Krzysztof Sworczak; Albert de la Chapelle Journal: J Clin Endocrinol Metab Date: 2015-08-14 Impact factor: 5.958
Authors: Yanqiang Wang; Huiling He; Wei Li; John Phay; Rulong Shen; Lianbo Yu; Baris Hancioglu; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2017-01-03 Impact factor: 11.205
Authors: Marissa Penna-Martinez; Friederike Epp; Heinrich Kahles; Elizabeth Ramos-Lopez; Nora Hinsch; Martin-Leo Hansmann; Ivan Selkinski; Frank Grünwald; Katharina Holzer; Wolf O Bechstein; Stefan Zeuzem; Christian Vorländer; Klaus Badenhoop Journal: Thyroid Date: 2014-01-29 Impact factor: 6.568
Authors: Huiling He; Wei Li; Sandya Liyanarachchi; Mukund Srinivas; Yanqiang Wang; Keiko Akagi; Yao Wang; Dayong Wu; Qianben Wang; Victor Jin; David E Symer; Rulong Shen; John Phay; Rebecca Nagy; Albert de la Chapelle Journal: Proc Natl Acad Sci U S A Date: 2015-04-27 Impact factor: 11.205