Increased Papillary Thyroid Cancer Risk Research Articles

Association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with papillary thyroid carcinoma: A case-control study.

Papillary thyroid cancer (PTC) is the most common type of thyroid cancer which its precise etiology remains unknown. However, environmental and genetic factors contribute to the etiology of PTC. Axis inhibition protein 1 (Axin1) is a scaffold protein that exerts its role as a tumor suppressor. In addition, Cathepsin B (Ctsb) is a cysteine protease with higher expression in several types of tumors. Therefore, the aim of this study was to investigate the possible association of AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms with PTC susceptibility. In total, 156 PTC patients and 158 sex-, age-, and BMI-matched control subjects were enrolled in the study. AXIN1 rs12921862 C/A and rs1805105 G/A and CTSB rs12898 G/A polymorphisms were genotyped using the PCR-RFLP method. There was a relationship between AXIN1 rs12921862 C/A polymorphism and an increased risk of PTC in all genetic models except the overdominant model. The AXIN1 rs1805105 G/A polymorphism was associated with an increased PTC risk only in codominant and overdominant models. The frequency of AXIN1 Ars12921862 Ars1805105 haplotype was higher in the PTC group and also this haplotype was associated with an increased risk of PTC. Moreover, the AXIN1 rs12921862 C/A polymorphism was not associated with PTC clinical and pathological findings, but AXIN1 rs1805105 G/A polymorphism was associated with almost three folds of larger tumor size (≥1cm). There was no association between CTSB rs12898 G/A polymorphism and PTC and its findings. The AXIN1 rs12921862 C/A and rs1805105 G/A polymorphisms were associated with PTC. AXIN1 rs1805105 G/A polymorphism was associated with higher tumor size.

Exposure to Polybrominated Diphenyl Ethers and a Polybrominated Biphenyl and Risk of Thyroid Cancer in Women: Single and Multi-Pollutant Approaches.

Thyroid cancer incidence is the most rapidly increasing malignancy; rates are three times higher in women than men. Thyroid hormone-disrupting flame-retardant chemicals, including polybrominated diphenyl ethers (PBDE) and polybrominated biphenyls (PBB), may contribute to this trend. We investigated the relationship between PBDE/PBB exposure and papillary thyroid cancer (PTC) in 250 incident female papillary thyroid cancer cases and 250 female controls frequency-matched on age. Interviews and postdiagnostic serum samples were collected from 2010 to 2013. Serum samples were analyzed for 11 congeners. We calculated ORs and 95% confidence intervals (95% CI) using single-pollutant logistic regression models for continuous and categorical lipid-adjusted serum concentrations of PBDE/PBB, adjusted for age, alcohol consumption, and education. We applied three multi-pollutant approaches [standard multipollutant regression models, hierarchical Bayesian logistic regression modeling (HBLR), principal components analysis (PCA)] to investigate associations with PBDE/PBB mixtures. In single-pollutant models, a decreased risk was observed at the highest (>90th percentile) versus lowest (<median) category of BDE-209 concentrations (OR, 0.47; 95% CI, 0.23-0.98); an elevated PTC risk was observed at the highest versus lowest category of BB-153 concentrations (OR, 1.81; 95% CI, 0.96-3.39). In standard multi-pollutant models, an interquartile range increase in BDE-100 concentrations was associated with increased PTC risk (OR, 1.18; 95% CI, 1.01-1.38). HBLR and PCA yielded no statistically significant results. Our results using single- and multi-pollutant modeling do not generally support a positive association with PBDE/PBB and PTC risk. Prospective studies with more advanced statistical approaches to analyze mixtures and populations with higher exposures could reveal new insights.

Inverse Relationship of BMI to TSH and Risk of Papillary Thyroid Cancer in Surgical Patients

BackgroundObesity and thyroid cancer has increased in recent decades. Thyroid malignancy is linked with elevated thyroid-stimulating hormone (TSH) levels, which may have a positive association with body mass index (BMI). This study examines obesity and TSH level effect on papillary thyroid cancer (PTC) risk in a surgical population. MethodsA retrospective review of prospectively collected data for 991 patients who underwent thyroidectomy at a single institution was performed. Patients were stratified according to BMI into three groups: nonobese (18.5-29.9 kg/m2), obese (30-39.9 kg/m2), and morbidly obese (≥40 kg/m2). Further subdivisions into benign and malignant outcomes based on final pathology were compared with preoperative TSH levels. Subanalyses according to sex were also performed. ResultsOf 517 patients with PTC, rate of malignancy (ROM) decreased (55% versus 48% versus 41%, P < 0.05) as BMI increased with a concomitant decrease in average TSH levels (1.75 versus 1.69 versus 1.41 mU/L), respectively. According to sex, decreased ROM (53% versus 44% versus 42%, P < 0.05) and TSH (1.79 versus 1.70 versus 1.33 mU/L), respectively, with increased BMI was identified in women. However, decrease of ROM was not significant in men with increasing TSH levels as BMI increased. Male sex was associated with increased PTC risk (OR, 1.916; 95% CI, 1.331-2.759), whereas obesity with reduced PTC risk (OR, 0.736; 95% CI, 0.555-0.976). ConclusionsHigher BMI correlates with decreased PTC rates and lower TSH levels and suggests other factors may be involved in thyroid tumorigenesis. Obese patients with thyroid cancer should not be managed differently compared with nonobese patients.

Polymorphisms of the Highly Expressed IL-6 Gene in the Papillary Thyroid Cancer Susceptibility Among Chinese.

Papillary thyroid cancer (PTC) is the cardinal histologic type of thyroid cancer, which is the most prevalent kind of endocrine malignancy. The expression of IL-6 is found higher in thyroid carcinoma (THCA) samples than paired normal tissues based on The Cancer Genome Atlas (TCGA) and Genotype-Tissue expression (GTEx) database. In this study, we aimed to investigate the association between interleukin-6 (IL-6) polymorphisms and the PTC risk. A case-control study was designed using the following data: 241 PTC patients and 463 healthy controls. Five single nucleotide polymorphisms (SNPs) in IL-6 were selected and genotyped using Agena MassARRAY technology. Our results revealed that SNP rs1800796 was associated with an increased PTC risk in co-dominant model (p = 0.042) and dominant model (p = 0.027). Rs1524107 was also a risk factor for PTC susceptibility in co-dominant model (p = 0.003), dominant model (p = 0.002) and log-additive model (p = 0.044). Moreover, rs2066992 significantly increased the PTC risk in co-dominant model and dominant model (p = 0.011, p = 0.009, respectively). Additionally, rs2069837 variant elevated the PTC risk based on dominant model (p = 0.041). In silico analysis, GTEx results for rs1800796, rs1524107 and rs2066992 variants are known to be associated with IL-6 gene expression. Using HaploReg, we found rs1800796, rs1524107 and rs2066992 in LD with functional importance. Our study indicates that IL-6 variants may be a risk factor involved in the pathogenesis and development of PTC.

Fasting serum glucose, thyroid-stimulating hormone, and thyroid hormones and risk of papillary thyroid cancer: A case-control study.

This study was to investigate the association of fasting serum glucose (FSG), thyroid-stimulating hormone (TSH), and thyroid hormones with papillary thyroid cancer (PTC). A total of 649 participants were included in this case-control study. The associations of FSG, TSH, free triiodothyronine (FT3) and free thyroxine (FT4) with PTC were estimated using an unconditional logistic regression. Compared with the lowest quintile of TSH levels, odds ratios (ORs) and 95% confidence intervals (CIs) for association between PTC risk and highest quintile of TSH levels were 1.67 (95% CI, 0.99-2.83). However, this risk correlation was more significant in PTC cases with ≤1.0 cm tumor size (adjusted OR, 1.95; 95% CI, 1.08-3.54; adjusted P-trend, 0.05). The PTC risk was also inversely associated with the serum FT3 level in all participants (adjusted P-trend, 0.001), but positively associated with the serum FT4 (adjusted P-trend, 0.001) and FSG (adjusted P-trend, 0.01) levels. Among the participants without diabetes, the individuals with high FSG levels and abnormal TSH concentration had an increased PTC risk (adjusted OR, 3.38; 95% CI, 1.78-6.42). The current study provides evidence for the association of FSG, TSH, and thyroid hormones (FT3 and FT4) with PTC risk. However, larger relative studies are needed.

The endothelin 1 and endothelin receptor A gene polymorphisms increase the risk of developing papillary thyroid cancer.

The endothelin (EDN) axis (EDN1 and EDN1 receptor A, EDNRA) is involved in cellular growth, differentiation, invasiveness, and tumor progression in several cancers. We wanted to examine the possible impact of single nucleotide polymorphisms (SNPs) of EDN1 and EDNRA genes on papillary thyroid cancer (PTC) development and general characteristics of PTC. Study population consist of 113 PTC patients and 185 controls. EDN1 (G5665T, T-1370G) and EDNRA (C TT70G, G-231A) SNPs were investigated by real-time PCR. The GG genotype of EDNRA+70 SNP was associated with threefold increased PTC risk (p = 0.01), and the combined CG + GG genotype was 2.48 fold higher among PTC patients compared to controls. The variant EDNRA- 231 allele was overrepresented in PTC patients according to controls (p = 0.05). The combined GT + TT genotype of EDN1 5665 SNP was related with late (age after 40years) PTC onset (p = 0.04), and was more prominent among male patients with PTC according to females (p = 0.03). No significant associations between PTC and - 1370 SNP were found. There were no relationships between laboratory parameters and investigated polymorphisms. The EDNRA + 70 SNP was associated with PTC development. The EDN1 5665 SNP was linked with increased risk for late PTC onset and was more prominent among male patients with PTC.

Interaction Between XRCC1 Gene Polymorphisms and Obesity on Susceptibility to Papillary Thyroid Cancer in Chinese Han Population

Background/Aims: To investigate the association of several single nucleotide polymorphisms (SNPs) within XRCC gene and additional gene- environment interaction with papillary thyroid cancer (PTC) risk. Methods: Testing for Hardy-Weinberg equilibrium in controls was conducted using SNPstats (online software: http://bioinfo.iconcologia.net/SNPstats). Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combination among 5 SNPs within XRCC gene and obesity. Results: Logistic regression analysis showed that the C allele of rs861539 and T allele of rs1799782 were associated with increased PTC risk Adjusted ORs (95%CI) were 1.65 (1.23-2.12) and 1.61 (1.20-2.04). However There was no relation of rs25489 Rs25487 and rs13181 with PTC. The cross-validation consistency and the testing accuracy for each of the models were determined by GMDR analysis. One two-locus model (rs1799782 and obesity) had a testing accuracy of 62.11% Which was significant at the p < 0.01 level. The D’ value between rs1799782 and rs13181 within ERCC1 gene was more than 0.75 (0.825). So haplotype analysis was just conducted for rs1799782 and rs13181 using the SHEsis online haplotype analysis software. In all samples The haplotype C- A was observed most frequently in two groups With 49.46% and 55.79% in the PTC patients and controls Respectively. The results also indicated that haplotype T- C was significantly associated with increased PTC risk. Conclusion: The C allele of rs861539 and T allele of rs1799782 Interaction between rs1799782 and obesity and haplotype T- C were all associated with increased PTC risk.

Age at diagnosis and gender modify the risk of 9q22 and 14q13 polymorphisms for papillary thyroid carcinoma.

Papillary thyroid cancer (PTC) shows familial occurrence, and some susceptibility single nucleotide polymorphisms (SNPs) have been identified in FOXE1 and near the NKX2-1 locus. The aim of our study was to analyse the association of PTC risk with SNPs in FOXE1 (rs965513, rs1867277, rs1443434) and near the NKX2-1 locus (rs944289) in a Polish population, and, in the second step, the interac-tion between SNPs and patient-related factors (age at diagnosis and gender). A total of 2243 DNA samples from PTC patients and 1160 controls were included in the study. The SNP analysis was performed with the allelic discrimination technique. There were significant associations of all SNPs with PTC (rs965513 odds ratio [OR] = 1.72, p = 8 × 10-7; rs1867277 OR = 1.59, p = 1 × 10-6; rs1443434 OR = 1.53, p = 1 × 10-5; rs944289 OR = 1.52, p = 4 × 10-5). Logistic regression analysis revealed an increased PTC risk in the interaction of rs944289 with age at diagnosis (OR = 1.01 per year, p = 6 × 10-4) and a decreased PTC risk in the interaction of male gender with the GGT FOXE1 protective haplotype (OR = 0.69, p = 0.01). the association between PTC and all analysed SNPs was confirmed. It was also shown that patient-related factors modify the predisposition to PTC by increasing the risk for rs944289 per year of age, and by enhancing the protective effect of the FOXE1 GGT haplotype in men.

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

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.

Association study of single nucleotide polymorphisms in mature microRNAs and the risk of thyroid tumor in a Chinese population.

MicroRNAs (miRNAs) are small non-coding RNA molecules that are involved in a variety of cellular functions. Single nucleotide polymorphisms (SNPs) have been identified in mature miRNAs (mmSNPs), some of which have been linked to cancer risk; however, it is unclear which mmSNPs contribute to the susceptibility to thyroid tumors. In the present study, we examined the influence of selected mmSNPs on the risk of thyroid tumor. After systematic in silico screening, seventeen mmSNPs were identified and genotyped in a Chinese population including 828 patients with papillary thyroid cancer (PTC), 488 patients with benign thyroid tumor (BN), and 1038 cancer-free controls. Multivariate logistic regression analyses were conducted to evaluate the association of SNP genotypes and alleles with the risk of developing PTC and BN. Three SNPs (rs67106263 in mir-3144, GA versus GG, OR = 1.35, 1.09-1.68; rs4919510 in mir-608, CC versus GG/GC, OR = 0.76, 0.60-0.97; and rs79402775 in mir-933, AA versus GG/GA, OR = 1.76, 1.00-3.12) were associated with PTC risk. A combined effect of unfavorable genotypes was observed to give increased PTC risk in a dose-dependent manner. In addition, three SNPs (rs10061133 in mir-449b, rs79402775 in mir-933 and rs4919510 in mir-608) showed at least borderline correlations with the risk of BN. False-positive report probability was assessed for significant findings. The rs67106263 SNP was associated with the expression level of mir-3144 in thyroid tissue. These results indicate that mmSNPs may contribute to genetic susceptibility to thyroid tumors. Large validation and functional studies are required to further explore the role of mmSNPs in carcinogenesis.

Higher Body-Mass Index and Higher Percentage of Body Fat Are Associated with Increased Papillary Thyroid Cancer Risk

Higher Body-Mass Index and Higher Percentage of Body Fat Are Associated with Increased Papillary Thyroid Cancer Risk

Common obesity-related genetic variants and papillary thyroid cancer risk.

Epidemiologic studies have shown consistent associations between obesity and increased thyroid cancer risk, but, to date, no studies have investigated the relationship between thyroid cancer risk and obesity-related single-nucleotide polymorphisms (SNP). We evaluated 575 tag SNPs in 23 obesity-related gene regions in a case-control study of 341 incident papillary thyroid cancer (PTC) cases and 444 controls of European ancestry. Logistic regression models, adjusted for attained age, year of birth, and sex were used to calculate ORs and 95% confidence intervals (CI) with SNP genotypes, coded as 0, 1, and 2 and modeled continuously to calculate P(trend). Nine of 10 top-ranking SNPs (P(trend) < 0.01) were located in the FTO (fat mass and obesity associated) gene region, whereas the other was located in INSR (insulin receptor). None of the associations were significant after correcting for multiple testing. Our data do not support an important role of obesity-related genetic polymorphisms in determining the risk of PTC. Factors other than selected genetic polymorphisms may be responsible for the observed associations between obesity and increased PTC risk.