TSHR rs2288496 associated with thyroid hormone and predict the occurrence of lymph node metastasis of papillary thyroid cancer

Article type: Research Article

Authors: Su, Xuan^{a; 1} | Lin, Li-Wen^{b; 1} | Weng, Jie-Ling^{c; 1} | Chen, Shu-Wei^a | Yang, Xin-Hua^d | Zhou, Da-Lei^d | Long, Ya-Kang^d | Shao, Qiong^d | Ye, Zu-Lu^d | Peng, Jun-Ling^d | Deng, Ling^d | He, Cai-Yun^d | Yang, An-Kui^{a; *}

Affiliations: [a] Department of Head and Neck, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China | [b] Department of Clinical Laboratory, Eighth Affiliated Hospital of Guangxi Medical University, Guigang City Pepole’s Hospital, Guigang, Guangxi, China | [c] Department of Pathology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China | [d] Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, China

Correspondence: [*] Corresponding authors: An-Kui Yang, Department of Head and Neck, Sun Yat-sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, Guangdong 510060, China. Tel.: +86 20 8734 3451; E-mail: yangak@sysucc.org.cn. %****␣cbm-26-cbm190630_temp.tex␣Line␣100␣**** Cai-Yun He, Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, 651# Dongfeng Road East, Guangzhou, Guangdong 510060, China. Tel.: +86 20 8734 5669; E-mail: hecy@sysucc.org.cn.

Note: [1] Xuan Su, Li-Wen Lin and Jie-Ling Weng contributed equally to this work and share the first authorship.

Abstract: This study aimed to evaluate the association of potential functional tagging single nucleotide polymorphisms (tagSNPs) in BRAF and TSHR with papillary thyroid cancer (PTC). Two tagSNPs (rs6464149 and rs7810757) in BRAF and six tagSNPs (rs17630128, rs2075179, rs7144481, rs2371462, rs2268477, and rs2288496) in TSHR were genotyped in 300 cases of PTC and 252 healthy controls. There was no difference in the genotype frequencies of BRAF and TSHR between PTC patients and control subjects, suggesting no contribution of BRAF or TSHR polymorphisms to the susceptibility to PTC. We observed that a tagSNP located in the 3’ untranslated region of TSHR, rs2288496, could affect the incidence of lymph node metastasis (LNM). The variant TC and TC + CC genotypes conferred an increased risk of LNM (for TC vs. TT: odds ratio (OR) = 2.01, 95% confidence interval (CI): 1.07–3.77; P= 0.030; for TC + CC vs. TT: OR = 1.87, 95% CI: 1.04–3.39, P= 0.038). Moreover, subjects carrying variant genotypes had higher TSH levels and lower thyroxine (T4) and Anti-TG levels compared with those in subjects carrying common genotypes. Our findings showed that PTC patients carrying the TSHR rs2288496 TC and CC variants were associated with higher TSH level and lower T4 and Anti-TG levels and were prone to developing LNM. To confirm these results, additional studies and functional experiments, especially in other ethnic populations, are needed.

Keywords: BRAF, TSHR, TSH, polymorphism, differentiated thyroid cancer

DOI: 10.3233/CBM-190630

Journal: Cancer Biomarkers, vol. 26, no. 4, pp. 461-470, 2019