Etiology Of Thyroid Cancer Research Articles

In-utero and newborn factors and thyroid cancer incidence in adult women in the Sister Study cohort.

10560 Background: Thyroid cancer ranks as the fifth most common cancer in women globally, with 90% of cases classified as differentiated thyroid cancer (DTC). Currently, thyroid cancer etiology remains largely unknown, with childhood exposure to ionizing radiation and obesity among the few established modifiable risk factors. Considering that DTC is diagnosed at relatively younger ages compared to many other cancers, with higher incidence in females versus males, the current study aimed to investigate in-utero and newborn exposures in relation to adult female DTC incidence. Methods: From the Sister Study, a cohort of sisters of women with breast cancer living in the U.S. (including Puerto Rico), we included 47810 women who were cancer-free at baseline (2003–2009). At baseline, participants provided information on their birth and newborn characteristics, and characteristics of their parents before and during pregnancy. Using Cox proportional hazards regression models, we assessed the association between in-utero and newborn factors and self-reported DTC incidence during follow-up. The models were adjusted for attained age (timescale), race/ethnicity, BMI, smoking status, personal history of benign thyroid disease, educational level, household annual income, and Area Deprivation Index. Results: The median age at baseline of the study population was 55.4 (interquartile range [IQR]: 48.9-62.1). During follow-up (median: 13.1 years, IQR: 11.5-15), 233 women were diagnosed with DTC, with medical records available for 72% of cases. Factors associated with a higher incidence of DTC included gestational hypertension or hypertension-related disorders (15 exposed cases, HR= 1.87, 95%CI 1.10-3.16), and higher birth weight (for every additional kilogram HR=1.13, 95%CI 1.00-1.27). The HR for maternal pre-pregnancy or gestational diabetes was 2.33 (5 exposed cases, 95%CI 0.96-5.67). Conversely, being born at least two weeks before the due date was associated with a lower incidence (6 exposed cases, HR=0.35, 95%CI 0.15-0.79). These associations remained consistent when restricting to advanced-stage and large-sized DTCs. We observed no associations for participants’ birth order, time since last pregnancy of the participants' mother, multiple versus singleton birth, ever having been breastfed, parental smoking during pregnancy or age at delivery, maternal morning sickness, or paternal diabetes. Conclusions: In this study, maternal diabetes, maternal hypertension, and birth weight were associated with higher female DTC incidence while being born at least two weeks before the due date was associated with lower DTC incidence. These findings provide evidence that in-utero and newborn exposures may have a long-term influence on thyroid cancer development.

Exploring the Potential Association between COVID-19 and Thyroid Cancer: A Mendelian Randomization Study.

In order to address the ongoing debate surrounding the potential link between COVID-19 and thyroid cancer, our study was specifically designed to investigate the association between these two factors. We acquired summary data from a genome-wide association study (GWAS) concerning COVID-19 susceptibility and severity of COVID-19 in the European population, with a focus on their relationship with thyroid cancer. We applied three distinct methodologies to evaluate the causality between COVID-19 and thyroid cancer, employing Mendelian randomization (MR)-Egger, weighted median (WM), and inverse variance-weighted (IVW) approaches. Furthermore, we utilized a variety of techniques to assess pleiotropy and heterogeneity, including the MR-Egger intercept, MR-pleiotropy residual sum and outlier method (PRESSO), and Cochran's Q test. The MR analysis revealed associations between the susceptibility of COVID-19 and thyroid cancer (IVW odds ratio [OR]: 2.826, 95% confidence interval [CI]: [0.842, 9.483], P = 0.093) as well as between the risk of COVID-19 hospitalization and thyroid cancer (IVW OR: 1.630, 95% CI: [1.050, 2.529], P = 0.029). However, the relationship between COVID-19 and the occurrence of severe thyroid cancer cases was less evident (IVW OR: 1.061, 95% CI: [0.575, 1.956], P = 0.850). Our sensitivity analyses did not reveal any signs of horizontal pleiotropy or heterogeneity. Our MR study provided compelling evidence supporting a causal connection between the risk of COVID-19 hospitalization and thyroid cancer. Nevertheless, the MR results derived from genetic data do not support a causal link between susceptibility to COVID-19 and the risk of thyroid cancer or between very severe cases of COVID-19 and the risk of thyroid cancer. These findings have significant implications for further investigations into the impact of COVID-19 on health and the etiology of thyroid cancer.

Tumor Microbial Communities and Thyroid Cancer Development-The Protective Role of Antioxidant Nutrients: Application Strategies and Future Directions.

Thyroid cancer (TC), the most frequent malignancy of the endocrine system, has recorded an increasing incidence in the last decades. The etiology of TC remains at least partly unknown and, among modifiable risk factors, the gut microbiota and dietary nutrients (vitamins, essential microelements, polyphenols, probiotics) have been recognized to not only influence thyroid function, but exert critical effects on TC development and progression. Recent discoveries on the existence of tumor microbiota also in the TC microenvironment provide further evidence for the essential role of tumor microorganisms in TC etiology and severity, as well as acting as prognostic markers and as a potential target of adjuvant care in the treatment of TC patients. Therefore, in this review, we summarize current knowledge on the relationship of the tumor microbiome with the clinical tumor characteristics and TC progression, also illustrating the molecular mechanisms underlying this association, and how antioxidant nutrients may be used as a novel strategy to both control gut health and reduce the risk for TC. Furthermore, we discuss how new technologies might be exploited for the development of new foods with high nutritional values, antioxidant capability, and even attractiveness to the individual in terms of sensory and emotional features.

The Act of Diminishing the RTRAF Expression in Benign Thyroid Tissues Represents a Potential Method for Impeding the Progression of Malignancy in Cells

Background: Thyroid cancer is the most common endocrine cancer, and women are almost three times more likely to develop it than men. Objectives: The etiology of thyroid cancer at the genetic level remains elusive. However, a potential involvement of the RNA Transcription, Translation, and Transport Factor (RTRAF) gene in the pathogenesis of this malignancy has been postulated. This gene has been shown to govern the expression of proteins that exert regulatory effects on the transition from the G1 to S phase of the cell cycle. Methods: For this study, 22 papillary thyroid carcinoma (PTC) tissues and 22 healthy tissues were collected. Additionally, 10 benign goiter tissues and 10 healthy tissues were gathered. RNA molecules were fixed, and complementary DNA (cDNA) was produced. Specific primers were used to measure the RTRAF gene expression. Statistical analysis was conducted using REST 2009 software. Results: Upon assessing the quality and quantity of RNA, it was ascertained that the extracted RNA molecules exhibited minimal damage and were found to be appropriately concentrated for cDNA production. The amplification of the RTRAF gene was carried out accurately, as evidenced by the melting curve. A noteworthy decline in the RTRAF gene expression was detected in the benign goiter tissue compared to the adjacent healthy tissue, with a relative expression of 0.154 and a statistical value of P = 0.002. Conversely, there was no significant difference in the RTRAF gene expression between PTC and the adjacent healthy tissue, with a P-value of 0.808. Conclusions: The reduced RTRAF gene expression in benign thyroid tumors may hinder cancer cell growth, as no difference was observed between malignant PTC tumor tissues and their healthy tissues.

Machine learning-aided metallomic profiling in serum and urine of thyroid cancer patients and its environmental implications

The incidence rate of thyroid cancer has been growing worldwide. Thyroid health is closely related with multiple trace metals, and the nutrients are essential in maintaining thyroid function while the contaminants can disturb thyroid morphology and homeostasis. In this study, we conducted metallomic analysis in thyroid cancer patients (n = 40) and control subjects (n = 40) recruited in Shenzhen, China with a high incidence of thyroid cancer. We found significant alterations in serumal and urinary metallomic profiling (including Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Sr, Cd, I, Ba, Tl, and Pb) and elemental correlative patterns between thyroid cancer patients and controls. Additionally, we also measured the serum Cu isotopic composition and found a multifaceted disturbance in Cu metabolism in thyroid disease patients. Based on the metallome variations, we built and assessed the thyroid cancer-predictive performance of seven machine learning algorithms. Among them, the Random Forest model performed the best with the accuracy of 1.000, 0.858, and 0.813 on the training, 5-fold cross-validation, and test set, respectively. The high performance of machine learning has demonstrated the great promise of metallomic analysis in the identification of thyroid cancer. Then, the Shapley Additive exPlanations approach was used to further interpret the variable contributions of the model and it showed that serum Pb contributed the most in the identification process. To the best of our knowledge, this is the first study that combines machine learning and metallome data for cancer identification, and it supports the indication of environmental heavy metal-related thyroid cancer etiology.

Patterns of Thyroid Cancer Mortality and Incidence in Saudi Arabia: A 30-Year Study.

Thyroid cancer is the most prevalent endocrine cancer among the female population in the Kingdom of Saudi Arabia (KSA) and the ninth most common in the male population in Saudi Arabia. Over the past years, an increasing incidence of thyroid cancer has been reported in Saudi Arabia. However, the etiology of thyroid cancer is still not clear. Therefore, this study aimed to estimate thyroid cancer incidence and mortality trends in Saudi Arabia from 1990 to 2019. The current study utilized the Global Burden of Disease and the Institute for Health Metrics and Evaluation databases to extract prevalence data of thyroid cancer in Saudi Arabia from 1990 to 2019. Moreover, the current project utilizes Global Burden of Disease (GBD) web-based tools to visualize these data. In total, 23,846 cases (17,220 females and 6626 males) were diagnosed with thyroid cancer in Saudi Arabia from 1990 to 2019. The incidence is higher in females than in males. Over these 30 years, women's incidence steadily increased by 15-fold versus a 22-fold increase in men. Moreover, there were 2056 deaths in total caused by thyroid cancer in KSA. The mortality rate in women steadily increased by threefold in the same period. However, the increase in mortality was higher in males (sixfold). A high percentage of YLLs was observed in males, with around 24.8% ranging from 30 to 34 and 40 to 45 years. Thyroid cancer incidence rates have increased exponentially between 1990 and 2019. The expansion of the incidence of thyroid cancer in Saudi Arabia could be due to the increased development in detection and diagnosis. The current study provided evidence of the need to increase awareness and diagnosis in the male population.

What do patients want to know about surgery for low-risk thyroid cancer? A qualitative study

BackgroundShared decision-making about treatment for low-risk thyroid cancer requires patients and surgeons to work together to select treatment that best balances risks and expected outcomes with patient preferences and values. To participate, patients must be activated and ask questions. We aimed to characterize what topics patients prioritize during treatment decision-making. MethodsWe identified substantive questions by patients with low-risk (cT1-2, N0) thyroid cancer during audio-recorded consultations with 9 surgeons at 2 unique health care systems. Logistics questions were excluded. Qualitative content analysis was used to identify major themes among patients’ questions and surgeon responses. ResultsOverall, 28 of 30 patients asked 253 substantive questions, with 2 patients not asking any substantive questions (median 8, range 0–25). Patients were 20 to 71 years old, mostly White (86.7%) and female (80.0%). The questions addressed extent of surgery, hormone supplementation, risk of cancer progression, radioactive iodine, and etiology of thyroid cancer. When patients probed for a recommendation regarding extent of surgery, surgeons often responded indirectly. When patients asked how surgery could impact quality of life, surgeons focused on oncologic benefits and surgical risk. Patients commonly asked about hormone supplementation and radioactive iodine. ConclusionPatient questions focused on the decision regarding extent of surgery, quality of life, and nonsurgical aspects of thyroid cancer care. Surgeon responses do not consistently directly answer patients’ questions but focus on the risks, benefits, and conduct of surgery itself. These findings suggest an opportunity to help surgeons with resources to improve shared decision-making by providing information that patients prioritize.

Fyn and Lyn gene polymorphisms impact the risk of thyroid cancer.

Thyroid cancer is the most common malignancy of the endocrine glands, and during last couple of decades, its incidence has risen alarmingly, across the globe. Etiology of thyroid cancer is still debatable. There are a few worth mentioning risk factors which contribute to initiation of abnormalities in thyroid gland leading to cancer. Genetic instability is major risk factors in thyroid carcinogenesis. Among the genetic factors, the Src family of genes (Src, Yes1, Fyn and Lyn) have been implicated in many cancers but there is little data regarding the association of these (Src, Yes1, Fyn and Lyn) genes with thyroid carcinogenesis. Fyn and Lyn genes of Src family found engaged in proliferation, migration, invasion, angiogenesis, and metastasis in different cancers. This study was planned to examine the effect of Fyn and Lyn SNPs on thyroid cancer risk in Pakistani population in 500 patients and 500 controls. Three polymorphisms of Fyn gene (rs6916861, rs2182644 and rs12910) and three polymorphisms of Lyn gene (rs2668011, rs45587541 and rs45489500) were analyzed using Tetra-primer ARMS-PCR followed by DNA sequencing. SNP rs6916861 of Fyn gene mutant genotype (CC) showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs2182644 of Fyn gene, mutant genotype (AA) indicated statistically significant 17-fold increased risk of thyroid cancer (P < 0.0001). Statistically significant threefold increased risk of thyroid cancer was observed in genotype AC (P < 0.0001) of Fyn gene polymorphism rs12910. In SNP rs2668011 of Lyn gene, TT genotype showed statistically significant threefold increased risk of thyroid cancer (P < 0.0001). In case of rs45587541 of Lyn gene, GA genotypes showed statistically significant 11-fold increased risk in thyroid cancer (P < 0.0001). Haplotype analysis revealed that AAATAG*, AGACAG*, AGCCAA*, AGCCAG*, CAATAG*, CGCCAG* and CGCCGA* haplotypes of Fyn and Lyn polymorphisms are associated with increased thyroid cancer risk. These results showed that genotypes and allele distribution of Fyn and Lyn are significantly linked with increased thyroid cancer risk and could be genetic adjuster for said disease.

Epidemiology of Thyroid Cancer.

Epidemiology of Thyroid Cancer.

Thyroid Cancer Diagnostics Related to Occupational and Environmental Risk Factors: An Integrated Risk Assessment Approach.

There are still many questions remaining about the etiopathogenesis of thyroid cancer, the most common type of endocrine neoplasia. Numerous occupational and environmental exposures have been shown to represent important risk factors that increase its incidence. Updated information about thyroid cancer diagnostics related to occupational and environmental risk factors is reviewed here, considering an integrated risk assessment approach; new data concerning thyroid cancer etiology and pathogenesis mechanisms, diagnostic biomarkers and methodologies, and risk factors involved in its pathogenesis are presented. A special emphasis is dedicated to specific occupational risk factors and to the association between environmental risk agents and thyroid cancer development. The occupational environment is taken into consideration, i.e., the current workplace and previous jobs, as well as data regarding risk factors, e.g., age, gender, family history, lifestyle, use of chemicals, or radiation exposure outside the workplace. Finally, an integrative approach is presented, underlying the need for an accurate Risk Assessment Matrix based on a systematic questionnaire. We propose a complex experimental design that contains different inclusion and exclusion criteria for patient groups, detailed working protocols for achieving coherent and sustainable, well-defined research stages from sample collection to the identification of biomarkers, with correlations between specific oncometabolites integrated into the Risk Assessment Matrix.

Thyroid cancer incidence and trends by demographic and tumor characteristics in Oran, Algeria: 1993-2013, a population-based analysis.

Incidence rates of thyroid cancer have dramatically increased over recent decades in many countries, particularly the papillary histotype and microcarcinomas. We examined thyroid cancer incidence and trends by demographic and tumor characteristics based on 1443 patients with thyroid cancer diagnosed between 1993 and 2013 in Oran district, in Northwest Algeria. All thyroid cancer cases were abstracted from medical records and pathology reports and classified according to the International Classification for Diseases in Oncology, third edition. Age-specific, age-standardized incidence rates per 100 000 person-years, and annual percent changes (APC) in the incidence were calculated. Age-standardized incidence was 11.7 per 100 000 for women and 2.0 per 100 000 for men. Thyroid cancer incidence increased over time significantly in women (APC: +3.72%; P < 0.05), mostly due to an increased incidence of the papillary histotype (APC: +5.48%; P < 0.05), and microcarcinomas (APC: +17.34%; P < 0.05). During the same time period, the incidence of follicular thyroid carcinomas decreased (APC: -3.74%; P < 0.05). The results of our study showing an upward trend of thyroid cancer incidence driven largely by increases in the papillary histotype are consistent with previous studies. The higher increase has coincided with the introduction of fine needle aspiration and thyroid ultrasound in the 1990s, and may have led to overdiagnosis. However, the increased papillary-to-follicular ratio observed over time is possibly a late effect of iodine supplementation implemented in Algeria in 1967 to combat endemic goiter. Further larger-scale population-based research is needed to gain insight into thyroid cancer etiology.

The effect of VAV3 polymorphisms on thyroid cancer.

The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population. We performed this case-control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants. We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model. Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.

Five genes influenced by obesity may contribute to the development of thyroid cancer through the regulation of insulin levels.

Previous studies indicate that obesity is an important contributor to the proceeding of thyroid cancer (TC) with limited knowledge of the underlying mechanism. Here, we hypothesize that molecules affected by obesity may play roles in the development of TC. To test the hypothesis above, we first conducted a large-scale literature-based data mining to identify genes influenced by obesity and genes related to TC. Then, a mega-analysis was conducted to study the expression changes of the obesity-specific genes in the case of TC, using 16 independent TC array-expression datasets (783 TC cases and 439 healthy controls). After that, pathway analysis was performed to explore the functional profile of the selected target genes and their potential connections with TC. We identified 1,036 genes associated with TC and 534 regulated by obesity, demonstrating a significant overlap (N = 176, p-value = 4.07e−112). Five out of the 358 obesity-specific genes, FABP4, CFD, GHR, TNFRSF11B, and LTF, presented significantly decreased expression in TC patients (LFC<−1.44; and p-value < 1e−7). Multiple literature-based pathways were identified where obesity could promote the pathologic development of TC through the regulation of these five genes and INS levels. The five obesity genes uncovered could be novel genes that play roles in the etiology of TC through the modulation of INS levels.

Research progress in the etiology of thyroid cancer

甲状腺癌是内分泌系统常见的恶性肿瘤，近年来其发病率呈明显上升趋势。甲状腺癌的发病机制及其病因尚不明确，目前已知可能的病因包括良性的甲状腺疾病、辐射、家族遗传、碘摄入量、雌激素等。通过对其病因及流行现状的研究，准确评估发病率增加的各项因素，进而对高危人群早期进行重点监测和干预，这对于早期预防、降低发病率具有重要意义。深入甲状腺恶性肿瘤的病因学研究，明确其恶变的关键环节，可能会提供新的治疗手段和靶点，所以甲状腺肿瘤恶变机制的研究非常重要。现将近年来甲状腺癌相对宏观的病因和流行现状的研究作一综述。.

Phytoestrogens and Thyroid Cancer Risk: A Population-Based Case-Control Study in Connecticut.

Very few previous studies have examined the relationship between thyroid cancer risk and intake of phytoestrogens (PE); furthermore, these studies have reached inconsistent results. We analyzed data from a population-based case-control study in Connecticut from 2010 to 2011, including 387 histologically confirmed thyroid cancer cases and 433 population-based controls, with compound data available concerning specific PEs. Multivariate unconditional logistic regression models were used to estimate the associations between specific PEs and the risk of thyroid cancer, adjusting for potential confounders. An elevated risk of thyroid cancer was associated with moderate to high levels of coumestrol intake [OR = 2.48, 95% confidence interval (CI), 1.39-4.43 for 40-80 μg/day; OR = 2.41, 95% CI, 1.32-4.40 for 80-130 μg/day; and OR = 2.38, 95% CI, 1.26-4.50 for >200 μg/day compared with <40 μg/day], and the main elevation in risk appeared among microcarcinomas (≤1 cm). A decreased risk of papillary macrocarcinomas (>1 cm; OR = 0.26, 95% CI, 0.08-0.85 for 1,860-3,110 μg/day compared with <760 μg/day) was associated with moderate genistein intake among women. Our study suggests that high coumestrol intake increases the risk of thyroid cancer, especially microcarcinomas, whereas moderate amounts of genistein intake appear to be protective for females with thyroid macrocarcinomas. The study highlights the importance of distinguishing between microcarcinomas and macrocarcinomas in future research on the etiology of thyroid cancer.

Birthweight and risk of thyroid cancer and its histological types: A large cohort study

BackgroundThe aetiology of thyroid cancer is poorly understood, but it is possible that this malignancy has origins early in life. It is, however, currently unknown if birthweight, as an indicator of prenatal growth, is related to thyroid cancer risk. ObjectiveTo investigate if birthweight is associated with the later risk of thyroid cancer and its histological types. Methods246,141 children (120,505 girls, 125,636 boys) from the Copenhagen School Health Records Register, born 1936–1989, were prospectively followed in the Danish Cancer Registry. Cox regressions were used to estimate hazards ratios (HR) and 95% confidence intervals (CI). ResultsDuring follow up, 241 individuals (172 women, 69 men) were diagnosed with thyroid cancer (162 papillary, 53 follicular). Birthweight was significantly and positively associated with risk of thyroid cancer overall (HR = 1.30 [95% CI: 1.03–1.64] per kilogram). There were no sex differences in the associations. Birthweight was positively and significantly associated with follicular thyroid cancer (HR = 1.74 [95% CI: 1.07–2.82] per kilogram), and although there was an indication of a positive association, it did not reach statistical significance for the more common papillary type (HR = 1.20 [95% CI: 0.90–1.59] per kilogram). ConclusionA heavier weight at birth is associated with an elevated risk of total and follicular thyroid cancer, which underscores that prenatal exposures may be important in thyroid cancer aetiology.

Lower Vitamin D Status in Patients with Differentiated Thyroid Carcinoma

Thyroid cancer (TC) has become the most rapidly increasing type of cancer representing 1-1.5% of all cancers diagnosed annually probably due to intensive screening. It is estimated that the death rate of TC has slowly increased from 0.49 to 0.51/100.000 in the last 10 years and 53.990 new cases will be diagnosed in 2018 in the United States. Therefore, efforts are being made in order to stop the increasing incidence and genetic alterations are thoroughly studied. One of the most recent incriminated factors in TC etiology and physiopathology is vitamin D deficiency. Besides the well-known role in bone metabolism, vitamin D has extra-skeletal effects exerted through the vitamin D receptor (VDR) and has been shown to interfere with many cellular functions such as inhibiting cell proliferation, stimulating differentiation and malignant cell apoptosis in different types of cancer. Cross-sectional, retrospective study which included 114 patients (71 with confirmed thyroid cancer and 43 patients in the control group with benign pathology). Preoperative levels of 25(OH)vitamin D, PTH, biochemical and thyroid panel were measured. The histopathologic features were analyzed. Mean values of vitamin D was 16.31 � 7.14 ng/mL with lower levels in patients with thyroid cancer (14.95 � 5.91 ng/mL) in comparison to patients with benign thyroid pathology (18.55 � 8.41 ng/mL), with a p value of 0.008. Majority of the cases were papillary thyroid cancer (97.18%) in stage 3 (45.07%). Vitamin D levels also correlated negatively with TNM staging. The necessity of further studies is a reality in order to establish if vitamin D deficiency is a possible risk factor for thyroid cancer and its correction can be considered an additional therapy.

Positive PIK3CA (P.H1047R) Mutation in a Benign Thyroid Nodule of a Patient With Men-1 Syndrome

ObjectiveThe PIK3CA (p.H1047R) mutation has only been identified in advanced poorly differentiated and anaplastic thyroid cancer in the past. We are describing the first reported case of this PIK3CA mutation in a benign thyroid nodule of a patient with multiple endocrine neoplasia type 1 (MEN-1) syndrome, which raises caution to the aggressive treatment approach usually taken when this mutation is identified.MethodsA 49-year-old female was found to have primary hyperparathyroidism with multigland disease and tested positive for MEN-1 syndrome. Further evaluation also identified a thyroid nodule, which had indeterminate cytology on fine-needle aspiration biopsy. The ThyroSeq 2.0 assay identified a PIK3CA mutation (p.H1047R, c.3140A>G), which led to a total thyroidectomy. Pathology showed a benign thyroid nodule.ResultsTo our knowledge, this is the first case reporting a PIK3CA (p.H1047R) mutation in a benign thyroid nodule, particularly in a patient with MEN-1 syndrome.ConclusionClinicians should be aware that this mutation can be identified in benign thyroid nodules and that aggressive management is not always warranted. Further research is needed to improve our understanding of thyroid cancer etiology and improve our ability to identify with high accuracy malignant and benign thyroid nodules when we are faced with indeterminate thyroid nodule cytology.

Radiation and Thyroid Cancer.

Radiation-induced damage is a complex network of interlinked signaling pathways, which may result in apoptosis, cell cycle arrest, DNA repair, and cancer. The development of thyroid cancer in response to radiation, from nuclear catastrophes to chemotherapy, has long been an object of study. A basic overview of the ionizing and non-ionizing radiation effects of the sensitivity of the thyroid gland on radiation and cancer development has been provided. In this review, we focus our attention on experiments in cell cultures exposed to ionizing radiation, ultraviolet light, and proton beams. Studies on the involvement of specific genes, proteins, and lipids are also reported. This review also describes how lipids are regulated in response to the radiation-induced damage and how they are involved in thyroid cancer etiology, invasion, and migration and how they can be used as both diagnostic markers and drug targets.

Inherited variants in genes somatically mutated in thyroid cancer.

BackgroundTumour suppressor genes when mutated in the germline cause various cancers, but they can also be somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic well-differentiated thyroid cancer (WDTC).MethodsWe performed a two-stage case-control association study with a total of 2214 cases and 2108 healthy controls from an Italian population. By genotyping 34 single nucleotide polymorphisms (SNPs), we covered a total of 59 missense SNPs and SNPs located in the 5' and 3' untranslated regions (UTRs) of 10 different genes.ResultsThe Italian1 series showed a suggestive association for 8 SNPs, from which three were replicated in the Italian2 series. The meta-analysis revealed a study-wide significant association for rs459552 (OR: 0.84, 95%CI: 0.75–0.94) and rs1800900 (OR: 1.15, 95%CI: 1.05–1.27), located in the APC and GNAS genes, respectively. The APC rs459552 is a missense SNP, located in a conserved amino acid position, but without any functional consequences. The GNAS rs1800900 is located at a conserved 5'UTR and according to the experimental ENCODE data it may affect promoter and histone marks in different cell types.ConclusionsThe results of this study yield new insights on WDTC, showing that inherited variants in the APC and GNAS genes can play a role in the etiology of thyroid cancer. Further studies are necessary to better understand the role of the identified SNPs in the development of WDTC and to functionally validate our in silico predictions.