Increased Risk Of Thyroid Cancer Research Articles

Elevated thyroid-stimulating hormone levels, independent of Hashimoto's thyroiditis, increase thyroid cancer risk: Insights from genetic and clinical evidence.

Hashimoto's thyroiditis (HT) is a prevalent autoimmune disorder and thyroid cancer (TC) is the most prevalent endocrine malignancy. Recent debates have focused on whether HT increases the risk of developing TC. This study combined Mendelian randomization (MR) and observational methods to investigate the potential causal relationship between HT and TC risk. First, we performed two-sample MR and multivariable MR (MVMR) analysis using the genome-wide association studies (GWAS) data from multiple databases, including European and East Asian populations, to estimate the effect of HT and thyroid-stimulating hormone (TSH) levels on TC risk. Second, we conducted an observational study using data from the National Health and Nutrition Examination Survey (NHANES) database and evaluated the association between HT, TSH, and TC prevalence through logistic regression model and restricted cubic spline model. Our MR findings revealed no significant association between HT and TC risk in both populations. However, elevated TSH levels significantly increased TC and papillary thyroid carcinoma (PTC) risk, while lower TSH levels were associated with reduced TC risk. Further MVMR analysis and an observational study confirmed this. Additionally, our observational study also indicated no significant relationship between HT and TC prevalence and abnormal TSH levels correlated with higher TC risk. HT was not a TC risk factor, but high TSH levels increased TC risk. Controlling TSH within normal ranges through thyroid hormone replacement was recommended to reduce TC risk in HT patients with elevated TSH levels, even those without symptoms.

HASHIMOTO THYROIDITIS IN PEDIATRICS: INSIGHTS INTO PATHOGENESIS, DIAGNOSIS, AND MANAGEMENT WITH CONSIDERATIONS OF CANCER RISK

This systematic review comprehensively examines the pathogenesis, diagnosis, management, and cancer risk of Hashimoto's thyroiditis in pediatric populations. We searched the literature using PubMed, Web of Science, and critical medical journals, focusing on studies published within a specified timeframe. Inclusion criteria targeted studies on pediatric populations, while exclusion criteria filtered out irrelevant studies. Data extraction and synthesis highlighted key findings: genetic predispositions and environmental triggers such as selenium levels and gut microbiota alterations contribute to Hashimoto’s Thyroiditis pathogenesis. Diagnostic challenges arise from the often subtle and nonspecific clinical presentation, necessitating thorough clinical evaluations and diagnostic testing, including TSH, free T4, thyroid antibodies, and ultrasound. Management strategies involve levothyroxine therapy, dietary considerations, and lifestyle modifications tailored to individual patient needs. Additionally, the review discusses the controversial but significant potential association between Hashimoto’s Thyroiditis and increased thyroid cancer risk, emphasizing the need for vigilant long-term monitoring. This synthesis provides critical insights to inform clinical practice and future research directions.

Association of serum lipids and abnormal lipid score with cancer risk: a population-based prospective study.

Serum lipid levels are associated with cancer risk. However, there still have uncertainties about the single and combined effects of low lipid levels on cancer risk. A prospective cohort study of 33,773 adults in Shanghai between 2016 and 2017 was conducted. Total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) levels were measured. Cox proportional hazard models were used to assess the association of single and combined lipids with overall, lung, colon, rectal, thyroid gland, stomach, and female breast cancers. The effect of the combination of abnormal lipid score and lifestyle on cancer was also estimated. A total of 926 incident cancer cases were identified. In the RCS analysis, hazard ratios (HRs) of overall cancer for individuals with TC < 5.18mmol/L or with LDL-C < 3.40mmol/L were higher. Low TC was associated with higher colorectal cancer risk (HR [95% CI] = 1.76 [1.09-2.84]) and low HDL-C increased thyroid cancer risk by 90%. Abnormal lipid score was linearly and positively associated with cancer risk, and smokers with high abnormal lipid scores had a higher cancer risk, compared to non-smokers with low abnormal lipid scores (P < 0.05). Low TC levels were associated with an increased risk of overall and colorectal cancer. More attention should be paid to participants with high abnormal lipid scores and unhealthy lifestyles who may have a higher risk of developing cancer. Determining the specific and comprehensive lipid combinations that affect tumorigenesis remains a valuable challenge.

Maternal Health, Pregnancy and Offspring Factors, and Maternal Thyroid Cancer Risk: A Nordic Population-Based Registry Study.

Thyroid cancer incidence is higher in women than men, especially during the reproductive years, for reasons that remain poorly understood. Using population-based registry data from 4 Nordic countries through 2015, we examined associations of perinatal characteristics with risk of maternal thyroid cancer. Cases were women diagnosed with thyroid cancer ≥2 years after last birth (n= 7,425, 83% papillary). Cases were matched to controls (n= 67,903) by mother's birth year, country, and county of residence. Odds ratios (ORs) were estimated using conditional logistic regression models adjusting for parity. Older age at first pregnancy, postpartum hemorrhage (OR= 1.18, 95% (confidence interval) CI: 1.08, 1.29), and benign thyroid conditions (ORs ranging from 1.64 for hypothyroidism to 10.35 for thyroid neoplasms) were associated with increased thyroid cancer risk, as were higher offspring birth weight (per 1-kg increase, OR= 1.17, 95% CI: 1.12, 1.22) and higher likelihood of offspring being large for gestational age (OR= 1.26, 95% CI: 1.11, 1.43). Unmarried/noncohabiting status (OR= 0.91, 95% CI: 0.84, 0.98), maternal smoking (OR= 0.75, 95% CI: 0.67, 0.84), and preterm birth (OR= 0.90, 95% CI: 0.83, 0.98) were associated with reduced risk. Several factors (e.g., older age at first pregnancy, maternal smoking, goiter, benign neoplasms, postpartum hemorrhage, hyperemesis gravidarum, and neonatal jaundice) were associated with advanced thyroid cancer. These findings suggest that some perinatal exposures may influence maternal thyroid cancer risk.

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.

Preexisting Thyroid Autoimmunity Is Associated with Increased Thyroid Cancer Risk

Preexisting Thyroid Autoimmunity Is Associated with Increased Thyroid Cancer Risk

Appraising the Effect of Potential Risk Factors on Thyroid Cancer: A Mendelian Randomization Study

Various risk factors have been associated with the risk of thyroid cancer in observational studies. However, the causality of the risk factors is not clear given the susceptibility of confounding and reverse causation. A 2-sample Mendelian randomization approach was used to estimate the effect of potential risk factors on thyroid cancer risk. Genetic instruments to proxy 55 risk factors were identified by genome-wide association studies (GWAS). Associations of these genetic variants with thyroid cancer risk were estimated in GWAS of the FinnGen Study (989 cases and 217 803 controls). A Bonferroni-corrected threshold of P = 9.09 × 10-4 was considered significant, and P < 0.05 was considered to be suggestive of an association. Telomere length was significantly associated with increased thyroid cancer risk after correction for multiple testing (OR 4.68; 95% CI, 2.35-9.31; P = 1.12 × 10-5). Suggestive associations with increased risk were noted for waist-to-hip ratio (OR 1.85; 95% CI, 1.02-3.35; P = 0.042) and diastolic blood pressure (OR 1.60; 95% CI, 1.08-2.38; P = 0.019). Suggestive associations were noted between hemoglobin A1c (HbA1c) (OR 0.20; 95% CI, 0.05-0.82; P = 0.025) and decreased risk of thyroid cancer. Risk of thyroid cancer was not associated with sex hormones and reproduction, developmental and growth, lipids, diet and lifestyle, or inflammatory factors (All P > 0.05). Our study identified several potential targets for primary prevention of thyroid cancer, including central obesity, diastolic blood pressure, HbA1c, and telomere length, which should inform public health policy.

Association of Metabolic Health and Central Obesity with the Risk of Thyroid Cancer: Data from the Korean Genome and Epidemiology Study.

It is unknown whether the risk of thyroid cancer differs among metabolically healthy/unhealthy, normal-weight, or obese women. We aimed to assess the association of metabolic health and obesity with thyroid cancer risk. The Korean Genome and Epidemiology Study is a population-based prospective cohort study. Data were obtained from 173,343 participants (age ≥40 years) enrolled from 2004 to 2013. Obese participants were those with body mass index (BMI) ≥25 kg/m2. Participants with abnormalities in three of these indices were considered metabolically unhealthy: triglycerides, blood pressure, high-density lipoprotein cholesterol (HDL-cholesterol), waist circumference (WC), and fasting glucose levels. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for thyroid cancer risk associated with metabolic health and obesity. Compared with nonobese women without metabolic abnormalities, metabolically unhealthy women, either normal weight or obese, had an increased risk of thyroid cancer [HR (95% CI) = 1.57 (1.02-2.40) and 1.71 (1.21-2.41), respectively). Significant association was not observed in men. Thyroid cancer risk was higher among nonobese women with high WC [≥85 cm; HR (95% CI) = 1.62 (1.03-2.56)] than in nonobese women with low WC, and in obese women with low HDL-cholesterol [<50 mg/dL; HR (95% CI) = 1.75 (1.26-2.42)] compared with nonobese women with high HDL-cholesterol. Metabolically unhealthy women or women with central adiposity may be at an increased thyroid cancer risk despite normal BMI. This study suggests that women with central obesity and metabolic abnormality despite normal BMI may constitute a target group for thyroid cancer prevention and control programs.

Genetic polymorphisms in the PCNXL2 gene are risk factors for thyroid cancer in the Chinese population.

Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45years, while this SNP decreased thyroid cancer risk at age ≤45years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45years. An association was observedbetween rs6424270and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938and rs4649295 was the best model to predict thyroid cancer. Conclusion: Thisstudy suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.

515Association between hysterectomy and risk of thyroid cancer

Abstract Background Hysterectomy (surgical removal of the uterus) has been consistently associated with increased thyroid cancer risk. While there may be a biologic explanation, increased ascertainment (over-diagnosis) because of greater healthcare use by women having this procedure might also contribute to the observed increased risk. We explored this association considering indications for hysterectomy, age at hysterectomy, and the potential for the association to be mediated by increased contact with health professionals or increased thyroid function testing. Methods We recruited 730 women diagnosed with thyroid cancer and 785 age-matched population controls. We estimated odds ratios (OR) using logistic regression to assess the associations and used causal mediation analysis to investigate potential mediation. Results Prior hysterectomy was associated with an increased thyroid cancer risk (OR = 1.55, 95% CI: 1.14-2.12). When stratified by indication for hysterectomy, the increased risk was apparent only among those who had undergone hysterectomy for bleeding disorders (OR = 1.79, 95% CI: 1.26-2.56). Additionally, the association varied by age at hysterectomy (&amp;lt;55 years, OR = 1.68, 95% CI: 1.22-2.31 versus ≥ 55 years, OR = 0.87, 95% CI: 0.42-1.81). Around 30% of the association was mediated by more frequent use of healthcare services. Conclusions Hysterectomy for bleeding disorders was associated with an increased risk of thyroid cancer among women and a moderate proportion of this appeared due to frequent medical contact. Key messages The way in which women use health services probably explains at least some of the association between hysterectomy and risk of thyroid cancer.

Risk of thyroid cancer following hysterectomy

BackgroundHysterectomy has been associated with increased thyroid cancer risk but whether this reflects a biological link or increased diagnosis of indolent cancers due to greater medical contact remains unclear. MethodsWe recruited 730 women diagnosed with thyroid cancer and 785 age-matched population controls. Multivariable logistic regression was used to assess the association overall, and by tumour BRAF mutational status as a marker of potentially higher-risk cancers. We used causal mediation analysis to investigate potential mediation of the association by healthcare service use. ResultsHaving had a hysterectomy was associated with an increased risk of thyroid cancer (odds ratio [OR] = 1.45, 95 % confidence interval [CI] 1.07–1.96). When stratified by indication for hysterectomy, the risk appeared stronger for those who had a hysterectomy for menstrual disorders (OR = 1.67, 95 % CI 1.17–2.37) but did not differ by tumour BRAF status. Approximately 20 % of the association between hysterectomy and thyroid cancer may be mediated by more frequent use of healthcare services. ConclusionsThe observed increased risk of thyroid cancer among those with hysterectomy may be driven, at least partly, by an altered sex steroid hormone milieu. More frequent healthcare service use by women with hysterectomy accounts for only a small proportion of the association.

Association of Polygenetic Risk Scores Related to Cell Differentiation and Inflammation with Thyroid Cancer Risk and Genetic Interaction with Dietary Intake.

Simple SummaryGlobal thyroid cancer incidence is increasing, especially in women. Genetic and environmental factors mutually contribute to its incidence. We aimed to identify genetic variants to influence thyroid cancer risk and determine their interactions with lifestyles in a large city hospital-based cohort (495 thyroid cancer patients and 56,439 control). The best polygenetic model included DIRC3_rs6759952, GAP43_rs13059137, NRG1_rs7834206, PROM1_rs72616195, LRP1B_rs1369535, and LOC100507065_rs11175834, tumorigenesis and cancer cell differentiation-related genes. Their high polygenetic risk scores (PRS) increased thyroid cancer risk by 3.90-fold compared to low-PRS. Thyroid cancer risk was elevated in females, high white blood cell counts, and high energy, low alcohol, and high seaweed intakes by 4.21, 4.03, 7.00, 4.11, and 4.02-fold, respectively. These factors interacted with PRS: the women with high-PRS elevated thyroid cancer risk much among women with high daily energy, seaweeds, and alcohol intake. These results could be applied to personalized nutrition plans to reduce thyroid cancer risk.The incidence of thyroid cancer continues to increase steadily, and this increasing incidence cannot be attributed solely to the overdiagnosis of microcarcinoma or technical advancements in detection methods and may also depend on environmental and genetic factors. However, the impacts and interactions of genetic and environmental factors remain controversial, and they may differ in Eastern and Western countries. The study’s purpose was to identify single nucleotide polymorphisms of genes related to cell differentiation and inflammation to influence thyroid cancer incidence and determine interactions with lifestyles in a large city hospital-based cohort. Genetic variants were selected by genome-wide association study with thyroid cancer participants (case; n = 495) and controls without cancers (n = 56,439). SNPs having gene–gene interactions were selected by generalized multifactor dimensionality reduction. Polygenic risk scores (PRSs) were generated by summing the number of selected SNP risk alleles. PRSs of the best model included 6 SNPs, that is, DIRC3_rs6759952, GAP43_rs13059137, NRG1_rs7834206, PROM1_rs72616195, LRP1B_rs1369535, and LOC100507065_rs11175834. Participants with a high-PRS had a higher thyroid cancer risk by 3.9-fold than those with a low-PRS. The following variables were related to an increased thyroid cancer risk; female (OR = 4.21), high white blood cell count (OR = 4.03), and high energy (OR = 7.00), low alcohol (OR = 4.11), and high seaweed (OR = 4.02) intakes. These variables also interacted with PRS to influence thyroid cancer risk. Meat/noodle diet patterns interacted with PRSs to increase thyroid cancer risk (p = 0.0023). In conclusion, women with a high-PRS associated with cell differentiation and inflammation were at an elevated thyroid cancer risk. Daily energy, seaweeds, and alcohol intake interacted with PRS for thyroid cancer risk. These results could be applied to personalized nutrition plans to reduce the risk of thyroid cancer.

Is the Increasing Incidence of Thyroid Cancer in the Nordic Countries Caused by Use of Mobile Phones?

The International Agency for Research on Cancer (IARC) at the World Health Organization (WHO) categorized in 2011 radiofrequency (RF) as a possible human carcinogen, Group 2B. During use of the handheld wireless phone, especially the smartphone, the thyroid gland is a target organ. During the 21st century, the incidence of thyroid cancer is increasing in many countries. We used the Swedish Cancer Register to study trends from 1970 to 2017. During that time period, the incidence increased statistically significantly in women with average annual percentage change (AAPC) +2.13%, 95% confidence interval (CI) +1.43, +2.83%. The increase was especially pronounced during 2010–2017 with annual percentage change (APC) +9.65%, 95% CI +6.68, +12.71%. In men, AAPC increased during 1970–2017 with +1.49%, 95% CI +0.71, +2.28%. Highest increase was found for the time period 2001–2017 with APC +5.26%, 95% CI +4.05, +6.49%. Similar results were found for all Nordic countries based on NORDCAN 1970–2016 with APC +5.83%, 95% CI +4.56, +7.12 in women from 2006 to 2016 and APC + 5.48%, 95% CI +3.92, +7.06% in men from 2005 to 2016. According to the Swedish Cancer Register, the increasing incidence was similar for tumors ≤4 cm as for tumors >4 cm, indicating that the increase cannot be explained by overdiagnosis. These results are in agreement with recent results on increased thyroid cancer risk associated with the use of mobile phones. We postulate that RF radiation is a causative factor for the increasing thyroid cancer incidence.

Plasma polybrominated diphenyl ethers, urinary heavy metals and the risk of thyroid cancer: A case-control study in China.

The incidence of thyroid cancer (TC) has increased rapidly worldwide in recent years. Exposure to endocrine disruptors can affect thyroid hormones and is probably carcinogenic to humans. The effects of polybrominated diphenyl ethers (PBDEs), some heavy metals (Cd, Pb, As and Hg) on risk of TC have been rarely reported. Hence, we aimed to examine the associations of TC risk with exposure to PBDEs and four heavy metals. This case-control study involved 308TC cases and 308 age- and sex-matched controls. Plasma PBDEs concentrations were determined by gas chromatograph-mass spectrometry. Concentrations of heavy metals concentrations in urine specimens were detected by graphite furnace atomic absorption spectrometry or inductively coupled plasma optical emission spectrometry. Conditional logistic regression models were used to explore associations of PBDEs and 4 heavy metals exposures with TC risk. A joint-effect interaction term was inserted into the logistic regression models to assess the multiplicative interaction effects of PBDEs-heavy metals on TC risk. Some PBDE congeners (BDE-028, -047,-099,-183,-209) were positively correlated with TC risk. As and Hg were also associated with the increased TC risk. Compared with low exposure levels, participants with high exposure levels of As and Hg were 5.35 and 2.98 times more likely to have TC, respectively. Co-exposure to BDE-209 and Pb had a negative interaction effect on TC risk. Some PBDE congeners (e.g. BDE-028, -047,-209) and Hg had a significant positive interaction effect on the risk of TC. The joint exposure of BDE-183 and Hg showed a negative interaction effect on TC risk, but the corresponding OR value was still statistically significant. Exposure to PBDEs, As and Hg may be associated with TC development. Joint exposure to PBDEs and Pb or Hg has interaction effects on TC risk. Further prospective research with large sample is required to confirm these findings.

Environmental exposure to cadmium and risk of thyroid cancer from national industrial complex areas: A population-based cohort study

BackgroundCadmium is known to act as a thyroid disruptor and carcinogen in humans. Recent evidence suggests that cadmium may play a role as a thyroid carcinogen due to its endocrine-disrupting activity, but this characterization remains unclear. ObjectiveWe investigated the association between urinary cadmium and primary thyroid cancer, and the modifying effect of diabetes on this association. MethodsWe included 5406 participants over 19 years old with measured urinary cadmium from samples collected at eight National Industrial Complex areas from 2003 to 2011. Among 5406 participants, 68 cases were diagnosed with thyroid cancer between enrollment and the end of follow-up (December 31, 2016). Incidence rate ratios for thyroid cancer were estimated using random-effects Cox proportional hazards models with follow-up time as the time scale. In addition, we conducted a stratified analysis by diabetes status. ResultsCompared with the lowest tertile, the middle and highest tertiles had higher risks of thyroid cancer, respectively (HRmiddle vs. lowest = 1.90, 95% CI = 0.93 to 3.91; HRhighest vs. lowest = 2.28, 95% CI = 1.09 to 4.78), with a significant dose-response relationship (P for trend = 0.03). There was no linear association between cadmium level and risk of thyroid cancer. Higher cadmium levels increased thyroid cancer risk in participants without diabetes (HRmiddle vs. lowest = 2.35, 95% CI = 1.05 to 5.24; HRhighest vs. lowest = 2.70, 95% CI = 1.18 to 6.19); although, an association between cadmium levels and thyroid cancer risk in participants with diabetes was not found. ConclusionLow-level exposure to cadmium is associated with thyroid cancer risk. Our results provide the evidence to limit exposure to cadmium for cancer prevention in the general population. Further studies are needed to investigate the consequence of diabetes and antidiabetic drugs between cadmium and thyroid cancer.

Association between Uranium Exposure and Thyroid Health: A National Health and Nutrition Examination Survey Analysis and Ecological Study.

Besides specific, incidental radiation exposure, which has been associated with increased thyroid cancer risk, the effects of exposure to background radiation from uranium, a naturally occurring, radioactive, and ubiquitous element, on the thyroid gland has not been widely studied. We therefore investigated the association between uranium exposure and thyroid health in the US. Using the National Health and Nutrition Examination Survey (NHANES), we assessed the association between urinary uranium levels and thyroid-related antibodies, including thyroglobulin antibodies (TgAb) and anti-thyroid peroxidase (anti-TPO), in the general population. Secondly, we performed an ecological study of age-adjusted thyroid cancer incidence rates per state and sources of uranium exposure. We included 3125 eligible participants from the NHANES and found a significant association between increased TgAb and increased urinary uranium levels when analyzed as quartiles (p = 0.0105), while no association was found with anti-TPO. In addition, although no significant correlation was found in the ecological study, certain states had high age-adjusted thyroid cancer incidence rates and a high number of uranium activity locations and high uranium concentrations in water. The present study suggests that uranium exposure may affect thyroid health, which warrants increased sampling of soil and water in high-risk states.

Risk of second primary papillary thyroid cancer among adult cancer survivors in the United States, 2000-2015

BackgroundWhile radiotherapy is a major risk factor for thyroid cancer after childhood cancer, factors contributing to increased thyroid cancer risk after adulthood cancer remain unclear. MethodsWe evaluated second primary papillary thyroid cancer (PTC) risk among 3,175,216 ≥ 1-year adult survivors of non-thyroid malignancies from US population-based cancer registries (2000–2015), using standardized incidence ratios (SIRs). Because heightened surveillance may increase detection of indolent thyroid tumors and earlier detection of advanced tumors, we examined SIRs by PTC stage and time since first cancer (latency). ResultsSIRs for second primary PTC (N = 4333) were statistically-significantly 1.2–3.5-fold elevated overall and after 23/27 first cancer types evaluated, with generally similar risks for localized and regional/distant PTC. SIRs for regional/distant PTC (N = 1501) were highest after pancreatic (SIR = 3.7; 95% confidence interval [CI] = 1.9–6.5) and soft tissue (SIR = 4.2; 95%CI = 2.8–6.2) cancers, followed by melanoma, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), diffuse large B-cell lymphoma, and larynx, kidney, and brain/central nervous system (SIRs = 2.0–2.9) cancers. SIRs typically decreased with increasing latency but remained statistically-significantly elevated for regional/distant-PTC ≥5 years after diagnosis of cancers of the rectum, pancreas, lung/bronchus, soft tissue, female breast, uterine corpus, prostate, and kidney, and after melanoma, Hodgkin lymphoma, CLL/SLL, and follicular lymphoma. Neither total nor regional/distant PTC were clearly associated with initial course of radiotherapy or chemotherapy. ConclusionsPTC risk was elevated after a range of first primary adult cancers but was not clearly related to treatment. Although surveillance may contribute to elevated short-term risks of PTC, longer-term elevations in regional/distant PTC may be attributable to shared risk factors.

Genetic Variants Implicate Dual Oxidase-2 in Familial and Sporadic Nonmedullary Thyroid Cancer

Highly penetrant hereditary thyroid cancer manifests as familial nonmedullary thyroid cancer (FNMTC), whereas low-penetrance hereditary thyroid cancer manifests as sporadic disease and is associated with common polymorphisms, including rs965513[A]. Whole-exome sequencing of an FNMTC kindred identified a novel Y1203H germline dual oxidase-2 (DUOX2) mutation. DUOX2Y1203H is enzymatically active, with increased production of reactive oxygen species. Furthermore, patients with sporadic thyroid cancer homozygous for rs965513[A] demonstrated higher DUOX2 expression than heterozygous rs965513[A/G] or homozygous rs965513[A]-negative patients. These data suggest that dysregulated hydrogen peroxide metabolism is a common mechanism by which high- and low-penetrance genetic factors increase thyroid cancer risk. SIGNIFICANCE: This study provides novel insights into the genetic and molecular mechanisms underlying familial and sporadic thyroid cancers.

IL1A & IL1B genetic polymorphisms are risk factors for thyroid cancer in a Chinese Han population

IntroductionThyroid carcinoma accounts for a large proportion of endocrine neoplasia, and the relationship between inflammation and thyroid cancer has been previously validated. IL-1α (Interleukin 1 alpha) and IL-1β (Interleukin 1 beta), encoded by IL1A and IL1B, respectively, are implicated in numerous inflammatory responses and in tumor progression. The objective of this research was to assess the association of genetic polymorphisms of IL1A and IL1B with the risk of thyroid cancer in a Chinese Han population. Materials and methodsGenotypes of the 12 candidate SNPs in IL1A and IL1B were identified among 208 thyroid cancer patients and 279 healthy controls using an Agena MassARRY method. Genetic model analysis was carried out to evaluate the significant links between the variants and thyroid cancer risk. HaploReg v4.1 and the GTEx database were used for SNP functional annotation and expression quantitative trait loci (eQTL) analysis, respectively. ResultsSignificant associations were detected between IL1A rs3783521 and an increased thyroid cancer risk in our study population (p < 0.05). IL1A rs3783546 and rs3783521 were associated with an increased cancer risk in men, and IL1B rs3136558 and rs1143623 were associated with an decreased cancer risk in women. Meanwhile, rs3783550, rs3783546, rs1609682, and rs3783521 in IL1A were identified as biomarkers of risk among individuals aged ≤48 years. Rs3136558 and rs1143623 in the IL1B gene showed strong correlations with a susceptibility to thyroid cancer among individuals aged >48 years. Additionally, bioinformatics and eQTLs analysis also provided supporting evidence for the effects of the SNPs on gene regulation. ConclusionsOur study is the first to report that IL1A and IL1B polymorphisms are risk factors for thyroid carcinoma in a Chinese Han population.