| Objective: To explore the association of TTF1 and TTF2 gene polymorphism with papillary thyroid cancer and provide gene evidence for diagnosis and treatment optimization of thyroid cancer.Methods:.1. A hospital-based case-control design was selected,case group:297 papillary thyroid cancer patients,control group:594 healthy controls which free of thyroid diseases. All the recruited subjects were Han Chinese with no genetic relationship with each other.All patients and healthy participants have no previous radiation exposure. None of the individuals had history of other cancer and received chemotherapy or radiotherapy.The cases and controls were well matched for age and sex.Clinicopathologic information were collected from electronic clinical and pathologic records. Genomic DNAs were extracted by Qiagen DNA blood kit from whole blood samples collected from all subjects. Two SNPs on TTF1 and TTF2 were genotyped by matrix-assisted laser desorption/ionization time-of-flight(MALDI-TOF) mass spectrometry in a hospital-based case-control study of 297 PTC patients and 594 healthy controls.2. Inclusion criteria of meta-analysis 1) the research purpose and statistical method of the literatures were similar; 2) The research object is thyroid carcinoma; 3) case-control design or Cohort study method; 4) the genotype distribution of the polymorphisms of TTF2 and TTF2 in cases and controls were described in details or the results were expressed as odds ratio(OR) and 95% confidence interval(95% CI). Published studies about the association of TTF1(rs9442891) and TTF2(rs965513) variations on papillary thyroid cancer were searched and retrievaled in Pub Med database, EMBase database, Medlin database, database of Wanfang, China National Konwledge Internet(CNKI), using the key words: Papillary Thyroid Cancer 、 TTF1(NKX2-1)、rs944289、TTF2(FOXE1)、rs944289、SNP(s)、gene、genetic、polymorphism(s). Finally, there were 16 literatures, which were eligible for the criteria to investigating the TTF1(rs9442891) and TTF2(rs965513) SNP. Publication bias was estimated by funnel plots and Egger’s linear regression test. STATA version 11.0 was used to perform all the statistical tests in the meta-analysis.Results:1. The twe group appeared to be matched well on sex and age, with P=0.918 and, P=0.840, respectively.All SNPs of cases and controls were in accordance with Hardy-Weinberg equilibrium.2. For rs944289,significant difference between the two groups was found in allele frequency distribution(Tvs C, P=0.017, OR=1.27, 95% CI=1.04–1.55). Compared with the homozygote CC genotype, a high PTC prevalence of the variant TT genotype was observed and found a significant elevateing ofPTC risk(TTvs CC,P=0.028,OR=1.53, 95% CI=1.05–2.24). Significant difference between the two groups was found as well in dominant frequency distribution(CT+TT vs CC, OR=1.34, 95% CI=1.00–1.79).3. For rs965513, it can also elevate the risk of PTC significantly in the allele model(Gvs A,P=0.014,OR=1.29, 95% CI=1.05–1.59),dominant model(AG+GGvs AA,P=0.031,OR=1.37,95% CI=1.09–1.82), and heterozygote model(AGvs AA,P=0.022,OR=1.67, 95% CI=1.07–2.59).4. For rs944289, patients with MNG can elevate the risk of PTC significantly in the allele model and in the dominant model(allele model:OR=1.72,95%CI=1.38–2.14;dominant:OR=2.267,95%CI=1.58–3.23); patients without metastasis can elevate the risk of PTC significantly in the allele model and in the dominant model(allele model:OR=2.07,95% CI=1.62–2.63;dominant model:OR=2.35,95% CI=1.58–3.47).5. For rs965513, patients with MNG can increase the risk of PTC significantly in the allele model and in the dominant model(allele model:OR=1.32, 95% CI=1.05–1.66; dominant model:OR=1.43, 95% CI=1.04–1.97); existence of wild-type allele G for rs965513 can reduce the risk of metastasis significantly compared with allele A(allele model : OR=1.42,95% CI=1.11–1.81).6. For rs944289 C/T polymorphism, it can elevate the risk of PTC significantly in the dominant model, homozygous model, andheterozygous model in the overall population; In the subgroup analysis by ethnicity,rs944289 mutation was significantly related with the risk of PTC in Asians in 5 models. Meanwhile, significant corrections were also found between rs944289 variant and PTC risk in Caucasian in the dominant model, homozygous model, and heterozygous model.7. Genotypes models and the allele model of rs965513 appeared to have significant associations in the overall population andsubgroup analysis of ethnicity.Summary:1. Rs944289 polymorphism of TTF1 is significantly associated with an increasing risk of PTC in Chinese.2. Rs965513 polymorphism of TTF2 is significantly associated with an increasing risk of PTC in Chinese.3. patients with MNG and no metastasis are more likely to suffer PTC.4. Through our meta-analysis, C/T variant of TTF1 and G/A mutation of TTF2 had a high correlation with PTC in the overall population. |
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