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Papillary thyroid cancer (PTC), one of the most common malignant thyroid tumors, exits widely in the thyroid of adolescents. Thyroid transcription factor 1 ( TTF1 ) and 2 ( TTF2 ) were thyroid-specific transcription factors, and regulated expression of the thyroid-specific genes. Hence, the aim of the present study was to evaluate the correlation between gene variants of  TTF1  and  TTF2  and the risk of PTC in Chinese population.  Two tagging single-nucleotide polymorphisms (tSNPs) on  TTF1  and  TTF2  were selected and genotyped by matrix-assisted laser desorption/ionization time-of-flight (MALDITOF) mass spectrometry in a hospital-based case-control study of 297 PTC patients and 594 healthy controls. Furthermore, a meta-analysis of the association between  TTF1  and  TTF2  and PTC risk was also performed.  We found that the rs944289 on the  TTF1  was significantly associated with increased PTC risk (TT vs CC, OR = 1.53, 95% CI = 1.05–2.24; CT + TT vs TT, OR = 1.34, 95% CI = 1.00–1.79; T vs C, OR = 1.27, 95% CI = 1.04–1.55). Similarly, the rs965513 on the  TTF2  can also elevate the risk of PTC significantly (GA vs GG, OR = 1.67, 95% CI = 1.07–2.59; AA+GA vs AA, OR = 1.37, 95% CI = 1.09–1.82; A vs G, OR = 1.29, 95% CI = 1.05–1.59). Furthermore, results of stratified analysis revealed that the risk effects of rs944289 and rs965513 were more overpowering in the subgroups of patients with MNG, as well as subjects without metastasis. Results of meta-analysis from the previous study and our new data indicated that variants of rs944289 and rs965513 might be the genetic susceptible factors both in Asians and Caucasians.  We get the conclusion that mutations of  TTF1  and  TTF2  are significantly associated with an increasing risk of PTC in Chinese. However, more detailed investigations and further large-scale studies on genetic functions to provide more conclusive and accurate evidence are required in the future.

Replication and Meta-Analysis of Common Gene Mutations in TTF1 and TTF2 with Papillary Thyroid Cancer