Risk Of Papillary Thyroid Carcinoma Research Articles

Clinical analysis of Hashimoto thyroiditis coexistent with papillary thyroid cancer in 1392 patients.

SUMMARYPapillary thyroid carcinoma (PTC) is the most common malignant tumour of the thyroid. The effect of the concurrent presence of Hashimoto's thyroiditis (HT) and PTC is still under debate. The aim of this study is to investigate the influence of coexistent HT on prognostic outcomes and the association of coexistent HT with clinicopathological features. The demographic and clinicopathological data of 1,392 patients who underwent surgery in our hospital from 2007 to 2016 was collected and analysed. Among 1,392 PTC patients, the rate of HT was 25.6%. There were significant differences in the mean levels of thyroid stimulating hormone (3.27 vs. 2.41 μIU/L, p < 0.01), thyroperoxidase antibodies (110.31 vs. 131.2 U/ml, p < 0.01) and thyroglobulin antibodies (131.90 vs. 113.53 ng/ml, p < 0.01) between the two groups. PTC patients with HT had the following characteristics compared to patients without HT: smaller tumour size (p < 0.01), female predominance (p < 0.01) and higher rate of multifocality (p = 0.024). In addition, patients with HT had a significantly lower rate of lymph node metastasis (LNM) and advanced TNM stage than patients without HT (all p < 0.01). Multivariate analysis found that both age and multifocality were significantly associated with central LNM in HT patients (p < 0.01, p = 0.019, respectively). Extrathyroidal invasion and TSH level were also significant independent factors for lateral LNM in HT patients (p < 0.008, p = 0.04, respectively). HT is associated with a significantly higher risk of PTC. The coexistence of HT in PTC patients is associated with favourable clinical outcomes compared to PTC without HT. Total thyroidectomy and prophylactic central compartment lymphadenectomy should be a choice for PTC patients with HT.

Establishment of risk score for papillary thyroid carcinoma and comparison of diagnostic efficacy with thyroid fine needle aspiration cytodiagnosis

To develop a simple and easy promotion risk score to identify individuals with undiagnosed papillary thyroid carcinoma (PTC), and further to compare the diagnostic efficiency of PTC risk sore with fine needle aspiration cytodiagnosis (FNAC). in order to optimize the screening process of PTC. A sample of 1 003 individuals aged 11-82 years underwent a surgical treatment of thyroid nodule participated in the study. The risk score was developed by stepwise backward multiple logistic regression. And using the receiver operating characteristic (ROC) curve to evaluate the diagnostic efficacy, the best diagnostic cut-off point and the risk stratification of malignant. Compare the sensitivity, specificity, accuracy, and area under curve (AUC) of PTC risk score, FNAC and their combined diagnosis to judge their diagnostic efficiency. The risk score included age, TSH, nodule morphology and boundary by palpation, nodule characteristics, shape, boundary, calcification and blood flow signal by ultrasound. Its AUC=0.815, 6 point was the best cutoff point to differentiate benign from malignant thyroid nodules, and risk stratification of thyroid carcinoma were divided into four levels: very high risk group (score ≥ 9 points), high risk group (score were 5-8 points), moderate risk group (score were 3~4 points), low risk group (score ≤ 2 points). The sensitivity, specificity, and accuracy of FNAC were 86.3%, 90.0%, and 87.0% respectively, AUC=0.891, while the sensitivity, specificity, and accuracy of PTC risk rating scale were 83.8%, 70.0%, and 81.0% respectively, AUC=0.822. The sensitivity, specificity, and accuracy of their combined diagnosis were 97.5%, 85.0%, and 95.0%, AUC=0.965. This risk score can be used as a screening method before FNAC. If combined with FNAC, it may improve the diagnostic efficacy of PTC, and thereby possibly minimizing the unnecessary invasive examination and surgical treatment for patients with thyroid nodules and reducing personal costs. (Chin J Endocrinol Metab, 2017, 33: 755-759) Key words: Thyroid papillary carcinoma; Scale; Risk score; Logistic regression analysis; Fine needle aspiration cytology; Diagnostic test

LAPTM4B*2 allele is associated with the development of papillary thyroid carcinoma in Chinese women.

Lysosome-associated protein transmembrane 4-β (LAPTM4B) contains a polymorphic region that contributes to the increased risk of numerous types of tumor. However, no study has yet demonstrated an association between the expression of the LAPTM4B gene and tumor differentiation, and the reason that LAPTM4B polymorphisms affect the susceptibility of individuals to cancer remains to be elucidated. The present study assessed the possible association between LAPTM4B polymorphism and the risk of papillary thyroid carcinoma (PTC), and attempted to identify the underlying mechanism for variation in patient susceptibility with respect to transcription regulation in the polymorphism region. The case control study included 183 papillary thyroid carcinoma patients (132 females, 51 males) and 697 healthy controls (249 females, 448 males). Genomic DNA was extracted from the blood and the genotype of LAPTM4B was identified using polymerase chain reaction (PCR). The results of the PCR revealed that LAPTM4B allele *2 was associated with PTC risk in comparison with LAPTM4B allele *1 [odds ratio (OR), 1.968; 95% confidence interval (CI), 1.363–2.841, P<0.001] in females, while LAPTM4B*2 was not associated with PTC risk in males (OR, 0.996, 95% CI, 0.615–1.612, P=0.986). Notably, LAPTM4B polymorphism was not associated with clinical parameters in the female patient group. In addition, by performing a luciferase reporter assay in the PTC TPC1 and B-CPAP cell lines, the transcriptional activity of the +10/+311 plasmid, representing LAPTM4B*2 was reduced compared with that of the +10/+292 plasmid representing LAPTM4B*1. In conclusion, the results of the present study suggested that LAPTM4B*2 was a susceptibility factor for PTC in the female Chinese population and this may not be caused by the transcriptional regulation of LAPTM4B polymorphism region in TPC1 and B-CPAP cell lines.

A meta-analysis of Hashimoto's thyroiditis and papillary thyroid carcinoma risk.

ObjectiveIt remains inconclusive whether Hashimoto’s thyroiditis (HT) predisposes patients to the development of papillary thyroid carcinoma (PTC). We conducted a meta-analysis of the available data to address this question.ResultsTwenty-seven eligible studies were selected, including 18 archival thyroidectomy studies, 6 fine-needle aspiration (FNA) studies, and 3 selective FNA or thyroidectomy studies. A total of 76,281 patients, including 12,476 cases of thyroid cancer, were included in these studies. The mean rate of PTC among patients with HT ranged from 1.12% (selective FNA or thyroidectomy studies) to 40.11% (thyroidectomy studies). All three types of studies supported the correlation between HT and PTC. The overall pooled odds ratio (OR) of the PTC risk for HT (HT versus non-HT) was 2.12 (95% confidence interval [CI]: 1.78-2.52).MethodsWe searched all relevant published studies using the citation databases PubMed and Embase. The ORs and corresponding 95% CIs were calculated by the random-effects model for the association between HT and PTC.ConclusionsOur meta-analysis confirmed that HT predisposed patients to the development of PTC.

Investigation of DNA repair-related SNPs underlying susceptibility to papillary thyroid carcinoma reveals MGMT as a novel candidate gene in Belarusian children exposed to radiation

BackgroundGenetic factors may influence an individual’s sensitivity to ionising radiation and therefore modify his/her risk of developing papillary thyroid carcinoma (PTC). Previously, we reported that common single nucleotide polymorphisms (SNPs) within the DNA damage recognition gene ATM contribute to PTC risk in Belarusian children exposed to fallout from the Chernobyl power plant accident. Here we explored in the same population the contribution of a panel of DNA repair-related SNPs in genes acting downstream of ATM.MethodsThe association of 141 SNPs located in 43 DNA repair genes was examined in 75 PTC cases and 254 controls from the Gomel region in Belarus. All subjects were younger than 15 years at the time of the Chernobyl accident. Conditional logistic regressions accounting for radiation dose were performed with PLINK using the additive allelic inheritance model, and a linkage disequilibrium (LD)-based Bonferroni correction was used for correction for multiple testing.ResultsThe intronic SNP rs2296675 in MGMT was associated with an increased PTC risk [per minor allele odds ratio (OR) 2.54 95% CI 1.50, 4.30, Pper allele = 0.0006, Pcorr.=0.05], and gene-wide association testing highlighted a possible role for ERCC5 (PGene = 0.01) and PCNA (PGene = 0.05) in addition to MGMT (PGene = 0.008).ConclusionsThese findings indicate that several genes acting in distinct DNA repair mechanisms contribute to PTC risk. Further investigation is needed to decipher the functional properties of the methyltransferase encoded by MGMT and to understand how alteration of such functions may lead to the development of the most common type of thyroid cancer.

Association of body mass index and the risk of papillary thyroid carcinoma

Objective To investigate the correlation between body mass index(BMI) and the occurence of papillary thyroid carcinoma(PTC)among the patients with thyroid nodules. Methods This cross-sectional study collected the data of 4 350 patients with thyroid nodules who underwent thyroidectomy in our hospital from January 1994 to December 2013. The patients were divided into normal weight(BMI 18.50~23.9 kg/m2), overweight(BMI 24.0~27.9 kg/m2), and obese(BMI≥28.0 kg/m2)groups according to BMI, as well as benign nodules and papillary thyroid carcinoma groups based on their pathological finding. The differences of age-sex composition, nodule diameter, TSH level, overweight and obese constituent ratio between two groups were also analyzed. Logistic regression method was used to evaluate the risk factors of PTC. Results (1)Compared with the benign nodule group, there was a higher proportion of patients under the age of 40 years(34.1% vs 19.5%, P<0.01)in PTC group, with smaller tumour diameters [ 1.0(0.7-2.0)cm vs 3.0(2.0-4.0)cm, P<0.01]and higher TSH levels [ 1.9(1.2-3.0)mU/L vs 1.6(0.9-2.5)mU/L, P<0.01]. (2)The proportion of obese patients was higher in PTC group than that in the benign nodule group(28.7% vs 20.7%, P<0.01)among male patients. While the difference was not found among female patients.(3)Stratification analysis according to gender and age showed that the proportion of overweight(49.4% vs 44.1%, P<0.05)or obese(26.5% vs 15.3%, P<0.01)in PTC group was higher than that of benign nodule group among male patients aged≤40 years and the proportion of obese patients in PTC group was higher than that of benign nodule group(30.8% vs 22.2%, P<0.01)among male patient aged 41 to 65 years.(4)A multivariate analysis indicated that overweight(OR=4.947)and obesity(OR=7.648)were all independent risk factors for PTC(P<0.01)among male patients aged≤40 years. Conclusion Overweight and obesity are associated with higher PTC risk for male patients aged 40 years or less. (Chin J Endocrinol Metab, 2017, 33: 296-300) Key words: Body mass index; Papillary thyroid carcinoma; Gender

The p.G534E variant of HABP2 is not associated with sporadic papillary thyroid carcinoma in a Polish population.

Thyroid cancer is one of the most frequently diagnosed cancers of the endocrine system. There are no known genetic risk factors for non-medullary thyroid cancer, other than a small number of hereditary syndromes; however, approximately 5% of non-medullary thyroid cancer, designated familial non-medullary thyroid cancer, exhibits heritability. The p.G534E (c.1601G>A) variant of HABP2 was recently reported as a risk factor for familial non-medullary thyroid cancer, including papillary thyroid carcinoma. We analyzed the incidence of the c.1601G>A variant of HABP2 in a Polish population consisting of 326 cases of papillary thyroid carcinoma and 400 control individuals by DNA genotyping, performed by Sanger sequencing. The c.1601G>A variant was detected in 3.7% of sporadic papillary thyroid carcinoma cases and 4.7% of healthy controls, and we did not detect an association between this variant and sporadic papillary thyroid carcinoma risk (OR = 0.71, 95% CI: 0.33–1.51; p = 0.3758). Additionally, no significant associations were identified between clinical and pathological disease features, response to primary treatment, and clinical status at the end of the observation, and HABP2 c.1601G>A genotype. In conclusion, the p.G534E variant of HABP2 is not associated with sporadic papillary thyroid carcinoma risk in the Polish population.

Expression characteristics of proteins of IGF-1R, p-Akt, and survivin in papillary thyroid carcinoma patients with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is related to increased risk of papillary thyroid carcinoma (PTC). Insulin-like growth factor-1 receptor (IGF-1R) is increased in patients with T2DM. The increased IGF-1R may be responsible for the development of PTC. In this study, we investigated the expression of phosphorylation of Akt (p-Akt)/survivin pathway activated by IGF-1R in PTC subjects with and without diabetes.Clinicopathological data of 20 PTC patients with T2DM were retrospectively analyzed and compared with those of 21 PTC subjects without diabetes. Meanwhile, IGF-1R, p-Akt, and survivin expressions of PTC tissues were detected by immunohistochemical staining.The immunohistochemical results found that the expression level of IGF-1R was significantly higher in diabetic PTC patients than that in nondiabetic PTC patients (P < 0.05). However, no significant differences of p-Akt and survivin expression were found between PTC patients with T2DM and PTC patients without T2DM. In addition, among 20 PTC patients with T2DM, subgroup analysis showed that the ratio of tumor size >10 mm was significantly higher in IGF-1R moderate to strong expression group than that in IGF-1R negative to weak expression group (P < 0.05).IGF-1R expression level was higher in PTC patients with T2DM, and the increased IGF-1R expression was associated with lager tumor size. IGF-1R may play an important role in carcinogenesis and tumor growth in PTC patients with T2DM.

The need of prophylactic central lymph node dissection is controversial in terms of postoperative thyroglobulin follow-up of patients with cN0 papillary thyroid cancer.

The objective of this study was to investigate whether prophylactic central lymph node dissection (pCLND) facilitates postoperative thyroglobulin (Tg) follow-up in the patients with papillary thyroid carcinoma (PTC). We also questioned whether radioactive iodine (RAI) remnant ablation provides any further advantage in this regard. The records of patients with low-intermediate risk PTC who underwent either only total thyroidectomy (TT) or TT in conjunction with pCLND were reviewed. Adjuvant RAI ablation was performed depending on tumor diameter, multifocality, the presence of positive lymph nodes and adverse histopathologic features. Pre-ablative and post-ablative Tg levels, post-operative complications and clinico-pathological characteristics were compared between the two groups (TT alone and TT with pCLND). Among the 302 patients, TT was performed in 140 (46.4%) and TT with pCLND in 162 (53.6%). More than half of all patients in both groups had papillary microcarcinoma (58.0% and 53,1%, respectively). Postoperatively, the median preablative Tg level was higher in the TT only group than that of the TT with pCLND group (0.96 vs 0.27ng/ml, respectively). The post-ablative Tg levels were undetectable in both groups at the last follow-up visit. Also, a subgroup of patients (19.5%) who did not receive RAI ablation all became athyroglobulinemic at one year after surgery. Although performing pCLND with TT seems to have an advantage over TT alone as to achieve lower Tg levels in the early post-operative period, Tg levels become comparable following RAI ablation. On the other hand, the patients who have not been treated with adjuvant RAI ablation, also became athyroglobulinemic regardless of the surgical method.

Association between single nucleotide variants of vascular endothelial growth factor A and the risk of thyroid carcinoma and nodular goiter in a Han Chinese population.

The aim of the present study was to investigate whether genetic variants in the vascular endothelial growth factor A gene (VEGFA) were risk factors for papillary thyroid carcinoma (PTC) or nodular goiter (NG) in Han Chinese. A total of 2,319 subjects (861 PTC patients, 562 NG patients, and 896 healthy controls) were included. Five tag single nucleotide polymorphisms (tagSNPs: rs3024997, rs3025040, rs833070, rs25648, and rs10434) in VEGFA were genotyped. SNP rs3025040 T allele was associated with a decreased risk of NG (P<0.05). SNP rs3024997 was associated with an increased risk of PTC (P<0.05) and NG (P<0.001) when an over-dominant model (AA+GG vs. AG) was considered. PTC patients carry the less frequent TT genotype (compared to the CC genotype) (P <0.05) of SNP rs3025040. Likewise, NG patients have the less frequent TC genotype compared to the CC (P <0.05). No significant association of SNPs rs833070, rs25648, and rs10434 with PTC or NG was observed. Haplotypes AT (rs3024997 and rs3025040) and GTA (rs10434, rs3025040, and rs3024997) showed a lower risk for NG (P <0.01 and P <0.05, respectively), while haplotypes GTT (rs833070, rs3025040, and rs3024997) and GGGT (rs833070, rs10434, rs3024997, and rs3025040) predicted the risk of progression to NG (both P <0.05). Haplotype AGAC (rs833070, rs10434, rs3024997, and rs3025040) conferred protection for PTC (P <0.05). In summary, this study indicated for the first time that SNPs rs3024997 and rs3025040 in VEGFA were significantly associated with PTC and/or NG. Haplotypes of the VEGFA may influence the risk of PTC and NG.

MYH9 binds to lncRNA gene PTCSC2 and regulates FOXE1 in the 9q22 thyroid cancer risk locus.

A locus on chromosome 9q22 harbors a SNP (rs965513) firmly associated with risk of papillary thyroid carcinoma (PTC). The locus also comprises the forkhead box E1 (FOXE1) gene, which is implicated in thyroid development, and a long noncoding RNA (lncRNA) gene, papillary thyroid cancer susceptibility candidate 2 (PTCSC2). How these might interact is not known. Here we report that PTCSC2 binds myosin-9 (MYH9). In a bidirectional promoter shared by FOXE1 and PTCSC2, MYH9 inhibits the promoter activity in both directions. This inhibition can be reversed by PTCSC2, which acts as a suppressor. RNA knockdown of FOXE1 in primary thyroid cells profoundly interferes with the p53 pathway. We propose that the interaction between the lncRNA, its binding protein MYH9, and the coding gene FOXE1 underlies the predisposition to PTC triggered by rs965513.

Variants in microRNA genes in familial papillary thyroid carcinoma.

Papillary Thyroid Carcinoma (PTC) displays one of the highest familiality scores of all cancers as measured by case-control studies, yet only a handful of genes have been implicated until now. Variants in microRNAs have been associated with the risk of several cancers including PTC but the magnitude of this involvement is unclear. This study was designed to test to what extent genomic variants in microRNAs contribute to PTC risk. We used SOLiD technology to sequence 321 genomic regions encoding 427 miRNAs in one affected individual from each of 80 PTC families. After excluding variants with frequency ≥ 1% in 1000 Genomes Phase 1 (n = 1092) we detected 1978 variants. After further functional filtering steps 25 variants in pre-miRs remained. Co-segregation was observed for six out of 16 tested miRNA variants with PTC in the families, namely let-7e, miR-181b, miR-135a, miR-15b, miR-320, and miR-484. Expression of miR-135a and miR-181b was tested in normal thyroid and tumor tissue from patients that carry the variants and a decrease in expression was observed. In vitro assays were applied to measure the effect of the variants on microRNAs’ maturation. Four out of six variants were tested. Only the let-7e and miR-181b variants showed an effect on processing leading to lower levels of mature miRNA. These two variants were not detected in 1170 sporadic PTC cases nor in 1404 controls. Taken together, our data show that high penetrance germline sequence variants of miRNAs potentially predispose to a fraction of all PTC but are not common.

Genotype Analyses in the Japanese and Belarusian Populations Reveal Independent Effects of rs965513 and rs1867277 but Do Not Support the Role of FOXE1 Polyalanine Tract Length in Conferring Risk for Papillary Thyroid Carcinoma.

Several functional single-nucleotide polymorphisms (SNPs) at the FOXE1 locus on chromosome 9q22.33 have been associated with the risk for papillary thyroid carcinoma (PTC). This study set out to elucidate whether their effects are independent, using genotyping results in populations of Asian and European descent. SNPs rs965513 and rs1867277 and a polymorphic region determining the length of the FOXE1 polyalanine (poly-Ala) tract were genotyped in 501 patients with PTC and 748 healthy individuals from Japan, and in 660 patients and 820 population controls from Belarus. Functional analysis of transactivation activities of FOXE1 isoforms with varying number of alanine repeats was performed by a Dual-Luciferase® Assay. All three polymorphisms were significantly associated with PTC in both populations on univariate analysis. However, conditional analysis revealed independent effects of rs965513 and rs1867277 SNPs but not of the FOXE1 poly-Ala polymorphism. The independent effect of the lead rs965513 SNP was observed in both populations, while that of rs1867277 was only identified in the Japanese population, in which linkage disequilibrium between the three polymorphisms is markedly weaker. Despite the strong decrease in transcriptional activity with increasing FOXE1 poly-Ala tract length, no difference in transactivation potential of the FOXE1 poly-Ala isoforms could be seen after adjustment for the minimal promoter activity in the reporter vectors. Plasmids encoding FOXE1 isoforms of increasing poly-Ala tract length were also found to produce less FOXE1 protein after cell transfection. The functional variants rs965513 and rs1867277 independently contribute to genetic predisposition to PTC, while a contributing role of the FOXE1 poly-Ala polymorphism could not be confirmed.

Association between IL-27 gene polymorphisms and risk of papillary thyroid carcinoma.

IL-27 has potent antitumor effects. We aimed to examine the contribution of single nucleotide polymorphisms in IL-27 to the risk of papillary thyroid carcinoma (PTC). IL-27 rs153109 and rs17855750 were analyzed in 496 PTC patients and 629 controls, using a polymerase chain reaction-restriction fragment length polymorphism method. The rs153109 AG and AG/GG genotypes were significantly associated with increased risks for PTC. Significantly increased PTC risk was also associated with rs17855750 GT and GT/GG genotypes. Combined genotypes of rs153109 AG/GG and rs17855750 GT/GG increased the risk of PTC (p < 0.05). These findings showed that IL-27 rs153109 and rs17855750 might be related to the tumorigenesis of PTC.

CT-detected solitary thyroid calcification: an important imaging feature for papillary carcinoma.

PurposeTo evaluate computed tomography (CT) detection of solitary thyroid calcification for identifying thyroid papillary carcinoma and to determine whether the predictive ability changes when the size increases after enhancement.Materials and methodsCT scans on all 96 patients with thyroid nodules who underwent both enhanced CT examination of neck and thyroidectomy from 2014 to 2016 in the Shandong Cancer Hospital affiliated to Shandong University were reviewed. The cases without calcification and the cases with peripheral calcification, multiple coarse calcifications, or punctate calcification were excluded. Imaging features, including location and size of the lesions, were reviewed on plain and contrast-enhanced CT. The patients were grouped by histological results. The comparisons were evaluated by using Fisher’s exact test and binary logistic regression.ResultsThe study population consisted of 96 patients (74 females, 22 males; mean age 49.8±11.3 years). Papillary thyroid carcinoma was observed in both solitary calcified thyroid nodules (85.4%) and solely coarse calcifications surrounded by low-density focus (58.2%). The difference was significant (P=0.006). Of 64 patients with an amplification of lesions after contrast enhancement, 58 (90.6%) were diagnosed with a malignant lesion. At the same time, of the 32 patients with no increase in size, 10 (31.2%) were diagnosed with carcinoma and 22 (68.8%) with nodular goiter. This difference was significant (P<0.001), and after binary logistic regression, increasing size was an independent risk factor for cancer.ConclusionSolitary calcified thyroid nodules detected on CT represent a high risk for papillary thyroid carcinoma, especially when the size of the lesions increases after contrast- enhanced CT.

Onco-lncRNA HOTAIR and its functional genetic variants in papillary thyroid carcinoma.

The role of long noncoding RNA (lncRNA) HOX transcript antisense RNA (HOTAIR) and its functional single nucleotide polymorphisms (SNPs) in papillary thyroid carcinoma (PTC) is still largely unclear. Therefore, we investigated the involvement of lncRNA HOTAIR and its three haplotype-tagging SNPs (htSNPs) in PTC. There was higher expression of HOTAIR in PTC tissues compared to normal tissues. A series of gain-loss assays demonstrated that HOTAIR acts as a PTC oncogene via promoting tumorigenic properties of PTC cells. Additionally, the functional HOTAIR rs920778 genetic variant was a PTC susceptibility SNP. Subjects with the HOTAIR rs920778 TT genotype had an odds ratio (OR) of 1.88, 1.25 and 1.61 (P = 6.0 × 10−6, P = 0.028 and P = 3.2 × 10−5) for developing PTC in Shandong, Jiangsu and Jilin case-control sets compared with subjects with the CC genotype. This statistically significant associations were only found between the rs920778 genetic polymorphism and PTC risk in females but not in males. The allele-specific regulation on HOTAIR expression by the rs920778 SNP was confirmed both in vitro and in vivo. Our results demonstrate that functional SNPs influencing lncRNA regulation may explain a part of PTC genetic basis.

Polymorphisms in selected DNA repair genes and cell cycle regulating genes involved in the risk of papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. In addition to causal somatic mutations in the BRAF gene and RET/PTC rearrangements, the contribution of single nucleotide polymorphisms (SNPs) in low-penetrance genes in the development of PTC has been proposed. Four SNPs in the XRCC1 (Arg399Gln, Arg280His, Arg194Trp and T-77C) and one SNP from each of three other genes participating in DNA repair pathways and/or cell cycle regulation (ATM Asp1853Asn, TP53 Arg72Pro, CDKN1B Val109Gly) were selected. The allelic and genotypic distributions of these variants as well as haplotypes of the XRCC1 were examined in 583 individuals comprising well-characterized cohorts of 209 PTC patients and 374 healthy volunteers. Correlations of polymorphism with clinical-pathological data and mutation status were performed. XRCC1 T-77C polymorphism affects the genetic susceptibility for PTC development in men, the specific combination of XRCC1 haplotypes correlates with RET/PTC incidence, CDKN1B Val109Gly significantly influences the risk of developing PTC regardless of gender and in PTC cases, selected genotypes of TP53 Arg72Pro and ATM Asp1853Asn were significantly associated with monitored tumour characteristics. It seems that SNPs in studied regulating genes contribute to the development of PTC and modify the tumour behaviour or characteristics.

Clinical Outcome of Radioiodine Therapy in Low-intermediate Risk Papillary Thyroid Carcinoma with BRAF(V600E) Mutation.

Objective To evaluate the impact of BRAF(V600E) gene status on clinical outcome of radioiodine((131)I) therapy in low-intermediate risk recurrent papillary thyroid carcinoma (PTC). Methods Totally 135 PTC patients were enrolled and divided into two groups according to BRAF(V600E) gene status:BRAF(V600E) mutation group(n=105) and BRAF(V600E) wild group(n=30). The median follow-up time was 2.16 years(1.03-4.06 years),and clinical outcome after initial (131)I ablation therapy was divided into excellent response(ER),acceptable response(AR),and incomplete response(IR) according to the serological and imageological follow-up results. The cinical outcomes were then compared between these two groups. Results There was no significant difference in clinicopathological features and initial radioactive iodine dose between BRAF(V600E) mutation and wild groups (P>0.05). ER,AR,and IR after (131)I ablation therapy accounted for 74.3%,20.0%,and 5.7% in BRAF(V600E) mutation group and 73.3%,20.0%,and 6.7% in BRAF(V600E) wild group,and no statistical difference was found (P=0.891). Conclusion For low-intermediate risk recurrent PTC,BRAF(V600E) gene status may have no impact on the response to (131)I ablation therapy,and thus this molecular feature should not be used as an independent weighting factor for risk assessment in this population.

Papillary thyroid carcinoma risk factors in the Yunnan plateau of southwestern China

ObjectiveThis study investigated clinical and pathological characteristics and risk factors in papillary thyroid carcinoma (PTC) patients’ native to Yunnan plateau in southwestern China.MethodsClinical data from 1,198 patients diagnosed with PTC (n=578) and control subjects (n=620) with benign thyroid disease (ie, thyroid nodule disease, benign thyroid diseases [BTD]) in Yunnan province were analyzed retrospectively.ResultsThe mean patient age was lower for PTC than for BTD. Positive ratios of thyroid peroxidase antibody, thyroglobulin antibody (TGAb), and thyrotrophin receptor antibody (TRAb) were higher in PTC than in BTD patients. The ratio of PTC coexisting with Hashimoto’s thyroiditis (HT) or with lymphocytic thyroiditis was higher than that of BTD. The number of patients whose age at menarche was ≤13 years, who had given birth to less than or equal to two children, or who were in premenopause were higher in the PTC than in the BTD group. Multivariate conditional logistic regression analyses revealed that age >45 years, nodal size >1 cm, and elevated TG levels were protective factors against PTC. Abnormally elevated TGAb and TRAb levels were independent risk factors for PTC in females.ConclusionHT was not an independent risk factor for but was associated with PTC. TRAb is a risk factor for PTC in individuals living in the Yunnan plateau, but not for those in the plains region.

Functional evaluation of TERT-CLPTM1L genetic variants associated with susceptibility of papillary thyroid carcinoma.

TERT is the catalytic subunit of telomerase which plays an essential part in cellular immortality by maintaining telomere integrity. TERT is commonly over-expressed in human malignancies, indicating its key role in cell transformation. The chromosome 5p15.33 TERT-CLPTM1L region has been associated with susceptibility of multiple cancers via a genome-wide association approach. However, the involvement of this locus in papillary thyroid carcinoma (PTC) etiology is still largely unknown. We analyzed 15 haplotype-tagging single nucleotide polymorphisms (htSNPs) of the TERT-CLPTM1L region in a two stage case-control design. After genotyping 2300 PTC patients and frequency-matched 2300 unaffected controls, we found that TERT rs2736100 genetic variant is significantly associated with elevated PTC risk. Ex vivo reporter gene assays indicated that the PTC susceptibility rs2736100 polymorphism locating in a potential TERT intronic enhancer has a genotype-specific effect on TERT expression. Correlations between rs2736100 genotypes and tissue-specific TERT expression supported the regulatory function of this genetic variant in vivo. Our data demonstrated that the functional TERT rs2736100 SNP as a novel genetic component of PTC etiology. This study, together with recent studies in other cancers, unequivocally establishes an essential role of TERT in cancers.