Risk Factor For Thyroid Cancer Research Articles

Chemotherapy and Thyroid Cancer Risk: A Report from the Childhood Cancer Survivor Study

Although ionizing radiation is an established environmental risk factor for thyroid cancer, the effect of chemotherapy drugs on thyroid cancer risk remains unclear. We evaluated the chemotherapy-related risk of thyroid cancer in childhood cancer survivors and the possible joint effects of chemotherapy and radiotherapy. The study included 12,547 five-year survivors of childhood cancer diagnosed during 1970 through 1986. Chemotherapy and radiotherapy information was obtained from medical records, and radiation dose was estimated to the thyroid gland. Cumulative incidence and relative risks were calculated with life-table methods and Poisson regression. Chemotherapy-related risks were evaluated separately by categories of radiation dose. Histologically confirmed thyroid cancer occurred in 119 patients. Thirty years after the first childhood cancer treatment, the cumulative incidence of thyroid cancer was 1.3% (95% CI, 1.0-1.6) for females and 0.6% (0.4-0.8) for males. Among patients with thyroid radiation doses of 20 Gy or less, treatment with alkylating agents was associated with a significant 2.4-fold increased risk of thyroid cancer (95% CI, 1.3-4.5; P = 0.002). Chemotherapy risks decreased as radiation dose increased, with a significant decrease for patients treated with alkylating agents (P(trend) = 0.03). No chemotherapy-related risk was evident for thyroid radiation doses more than 20 Gy. Treatments with alkylating agents increased thyroid cancer risk, but only in the radiation dose range less than 20 Gy, in which cell sparing likely predominates over cell killing. Our study adds to the evidence for chemotherapy agent-specific increased risks of thyroid cancer, which to date, were mainly thought to be related to prior radiotherapy.

Oxidative stress: a new risk factor for thyroid cancer

Oxidative stress (OS) is a state of excessive free radicals and reactive metabolites among which the most important class is reactive oxygen species (ROS) - radicals derived from oxygen - as represented by the superoxide anion radical (O2(·-)) and its reactive metabolites, hydroxyl radical (·OH) and hydrogen peroxide (H(2)O(2)). In essence, OS represents an imbalance between the production of oxidants - ROS - and their elimination by antioxidative systems in the body. Many studies have linked OS to thyroid cancer by showing its association with abnormally regulated oxidative or antioxidative molecules. The study by Wang et al. in the December 2011 issue of Endocrine-Related Cancer (18, 773-782) further supports this relationship by demonstrating a high total oxidant status and OS index in thyroid cancer patients. The origin of ROS in thyroid cancer patients has not been defined, but thyroid cancer itself can be one since inflammation, a major event in it, is a classical source of ROS. ROS may in turn enhance the mitogen-activated protein (MAP) kinase and phosphatidylinositol-3-kinase (PI3K) pathways, forming a vicious cycle propelling thyroid tumorigenesis. Regardless of the mechanism, the clinical implication of the association of OS with thyroid cancer is severalfold: one, OS is a new risk factor for thyroid cancer; two, OS confers thyroid cancer patients an increased risk for cardiovascular diseases, degenerative neurological disorders, and other cancers that are classically associated with OS; and three, interference with OS may reduce this risk and be therapeutically beneficial to thyroid cancer itself in thyroid cancer patients. These interesting possibilities deserve further studies.

Association between the serum TSH concentration and thyroid cancer incidence

To investigate the association between serum TSH concentration and thyroid cancer incidence. Three hundred and thirty patients with thyroid tumors who underwent surgical treatment were included in this study (99 cases of malignancy and 231 cases of benign tumors). The data of their serum TSH level, gender, age, tumor type, and number of tumors detected by ultrasonic inspection were retrospectively analyzed, and their association with thyroid cancer incidence was explored. The proportion of thyroid cancer in the groups of younger than twenty years and older than seventy years were 63.0% and 58.3%, respectively, significantly higher than that in the group of age between 60 and 69 years (23.3%, P < 0.05). The incidence of thyroid cancer of the 81 male patients was 43.2%, significantly higher than that in the 249 female patients (25.7%, P = 0.003). The incidence of thyroid cancer in the 112 patients with single nodule was 42.0%, significantly higher than that in the 218 patients with multiple nodules (23.9%, P < 0.001). In the groups with TSH level lower than 0.28 mIU/L and higher than 4.20 mIU/L, the incidence of thyroid cancer were 54.6% and 50.0%, respectively, significantly higher than that in the group with TSH level between 0.28 and 1.44 mIU/L (16.1%, P < 0.05). The proportion of patients with thyroid cancer was also increased with the increasing serum TSH level in the normal range (P < 0.001). High serum TSH level (OR = 1.465, P = 0.014), male (OR = 1.964, P = 0.016) and a single thyroid nodule (OR = 2.090, P = 0.006) are independent risk factors of thyroid cancer. The high serum TSH level, male, single thyroid nodule are factors leading to a high incidence of thyroid cancer.

Approach to the Thyroid Cancer Patient with Bone Metastases

Thyroid cancer incidence has been increasing for decades in the United States (1, 2). There are known risk factors for thyroid cancer including female gender, advancing age, family history, and radiation exposure, but none of these can fully explain the changing pattern of this disease over such a short period of time. Much of the rise has been attributed to increased medical surveillance, diagnostic imaging, and ultrasound-guided fine-needle aspiration (FNA), but this probably does not explain the entire observed upsurge. With increased evaluation of patients in an asymptomatic stage, it might be expected that the highest rate of increase would be seen in tumors of less than 1.0 cm, but incidence has also been increasing for tumors of any size, especially tumors at least 4 cm among men and women and for distant metastases among men (3). The more frequent diagnosis of late stage disease has led to the rising occurrence of differentiated thyroid carcinoma and bone metastases, even as the initial presentation of disease. It is suspected that a combination of environmental factors, iodine deficiency, and genetic factors (i.e. BRAF mutations) may explain the rising incidence of differentiated thyroid cancer, particularly more aggressive, late stage disease (4, 5).

Comparison of Exposures Among Arab American and Non-Hispanic White Female Thyroid Cancer Cases in Metropolitan Detroit

Arab American (ArA) women may be at greater risk for thyroid cancer (TC) than White women. This case-case comparison explored differences in known and proposed risk factors of TC among ArA and non-Hispanic White (NHW) female TC cases in metropolitan Detroit. Cases of invasive TC identified from a population-based registry responded to a telephone survey regarding potential TC risk factors. Thirty ArA women (response rate 52%) and 70 NHW women (67%) participated. NHW women reported significantly more prior thyroid disease (TD), family history of TD, hormone use, cumulative years of hormone use, cigarette and alcohol consumption. In adjusted logistic regression analysis, ArA women had significantly higher odds of exposure to dental x-rays (OR = 3.48, CI 1.01-12.00) and medical radiation (OR = 13.58, CI 1.49-124.04) than NHW women. Risk factors for TC may differ among ArA women and their NHW counterparts.

Épidémiologie des cancers thyroïdiens dans le monde

Thyroid cancer (TC) incidence, in France and over the world, has dramatically increased over the last two decades. The temporal and geographical incidence trends in France and in the world are analysed. The increased incidence of TC is actual, mainly due to an increase of papillary microcarcinomas. The spread of ultrasonographic and cytological procedures, the extensiveness of thyroidectomies lead to diagnostic advance, to a better preoperative selection of patients and to the discovery of occult microcarcinomas. Nevertheless, the impact of the risk factors of thyroid cancer on the increase of incidence is not excluded. These risk factors are analysed, especially environmental chemicals agents that disrupt thyroid function.

Risks of papillary and follicular thyroid cancer among immigrants to Sweden

Previous studies have indicated that ionizing radiation, particularly during childhood, is the main established risk factor for thyroid cancer. History of benign nodules/adenoma, goiter, iodine deficiency or high-iodine intake might be other associated factors. We wanted to define the histology-specific thyroid cancer risk in the first-generation immigrants to Sweden. We used the 2010 update of the nation-wide Swedish Family-Cancer Database (>12 million individuals; 1.8 million immigrants; histology code in force since 1958) to calculate standardized incidence ratios (SIRs) for histology-specific thyroid cancer among immigrants compared to the native Swedes. The patient series covered 2,604 male and 6,406 female Swedes, and 247 and 863 immigrants. The median age at immigration was 29 years, and the median age at thyroid cancer diagnosis was 46 years. Increased risks for female papillary carcinoma were observed for Finns (SIR = 1.63), former Yugoslavians (2.36), Russians (2.34), other East Europeans (2.14), Turks (3.16), Iranians (2.68), Iraqis (2.77), East and Southeast Asians (2.92), other Asians (1.69) and South Americans (2.23). Male Iranians (2.85), East and Southeast Asians (3.57) and other Asians (2.26) had an increased risk for papillary carcinoma. Only male East and Southeast Asians (2.93) had an increased risk for follicular carcinoma. The data might suggest that immigrant populations in Sweden from areas of low or high-iodine intake are at risk of papillary carcinoma, implicating iodine imbalance as a contributing factor to our findings. The increased risk of thyroid cancer among Asian immigrants may confirm the role of childhood-ionizing radiation on thyroid cancer risk.

Obesity and Thyroid Cancer Risk among U.S. Men and Women: A Pooled Analysis of Five Prospective Studies

Thyroid cancer incidence has risen dramatically in the United States since the early 1980s. Although the prevalence of obesity has doubled during this time period, the relationship between obesity and thyroid cancer is uncertain. We examined the association between body mass index (BMI) and thyroid cancer risk in a pooled analysis of five prospective U.S. studies, including 413,979 women and 434,953 men. Proportional hazards models with attained age as the time metric were adjusted for education, race, marital status, smoking, alcohol intake, and (where appropriate) cohort and sex. Over follow-up (mean=10.3 years), 768 women and 388 men were diagnosed with thyroid cancer. The risk of thyroid cancer was greater with increasing BMI [per 5 kg/m2: HR in women, 1.16 (95% CI, 1.08-1.24); HR in men, 1.21 (95% CI, 0.97-1.49)]. There was no significant heterogeneity between studies (both P>0.05). For women and men combined, the HRs for overweight (25.0-29.9 kg/m2) and obesity (≥30 kg/m2) compared with normal-weight (18.5-24.9 kg/m2) were 1.20 (95% CI, 1.04-1.38) and 1.53 (95% CI, 1.31-1.79), respectively. We found no significant effect modification by other factors, and the results did not differ significantly by histologic type. A significant positive association for BMI in young adulthood (ages 18-20) with thyroid cancer risk was also observed [per 5-kg/m2 increase: HR, 1.18 (95% CI, 1.03-1.35)]. BMI was positively associated with thyroid cancer risk in both men and women. Our study provides strong evidence that obesity is an independent risk factor for thyroid cancer.

Autoimmune Thyroid Disease: A Risk Factor for Thyroid Cancer

To examine the relationship between clinical markers of autoimmune thyroid disease and the risk of thyroid cancer in patients with thyroid nodules. A retrospective cohort analysis was performed in a single clinical practice. In 2,500 consecutive patients, fine-needle aspiration biopsy (FNAB) was performed on all 3,658 ultrasonography-positive thyroid nodules that were ≥ 1.0 cm in diameter or ≥ 0.5 cm in diameter with ultrasound features suspicious for thyroid cancer. Serum concentrations of thyroglobulin antibodies (TgAb), thyroid peroxidase antibodies, and thyroid-stimulating hormone were measured before FNAB. Diagnosis of thyroid cancer was based on pathologic analysis of thyroidectomy tissue. Associations of thyroid cancer with the independent variables were determined by multivariate logistic regression analysis and reported as the adjusted odds ratio (OR) with the 95% confidence interval (CI). There were 202 patients with malignant thyroid nodules, 51 patients with microscopic unsuspected thyroid cancer distal to the nodule under investigation (found at thyroidectomy), and 2,247 patients with benign thyroid nodules. To evaluate the association of clinical markers for autoimmune thyroid disease with thyroid cancer, we included all 253 patients with thyroid cancer in the malignant cohort. Thyroid cancer was associated with elevated levels of TgAb (OR = 1.57; CI = 1.11 to 2.23) and age <55 years (OR = 2.01; CI = 1.45 to 2.78), and a strong trend was demonstrated for association with male sex (OR = 1.45; CI = 0.99 to 2.12). Thyroid cancer was not associated with elevated levels of thyroid peroxidase antibodies. In patients who have thyroid nodules with indications for FNAB, elevated levels of TgAb are associated with thyroid cancer.

MicroRNA Dysregulation in Human Thyroid Cells Following Exposure to Ionizing Radiation

Ionizing radiation is a well-known mutagen and a risk factor for thyroid cancer. MicroRNAs (miRNAs) play an important role in the regulation of gene expression on post-transcriptional level and are dysregulated in thyroid cancer. The goal of this study was to investigate the effects of acute exposure to 1 and 10 Gy of γ-irradiation on miRNA expression in normal human thyroid cells. Expression of 319 miRNAs was studied in primary cultures of normal human thyroid cells 4 and 24 hours postirradiation using a miRNA expression array with further confirmation of miRNAs expression by reverse transcription-polymerase chain reaction. We identified 30 miRNAs that were unregulated or downregulated more than twofold after irradiation as compared to nonirradiated thyroid cells, with no significant difference found between 1 and 10 Gy of radiation. Four distinct patterns of miRNA expression change were observed: miRNAs downregulated at 4 hours and returned to normal levels at 24 hours, miRNAs upregulated at 4 hours and returned to normal levels at 24 hours, and miRNAs either upregulated or downregulated at both time points. No dysregulation of miRNAs known to occur in thyroid cancer was observed. Acute exposure of thyroid cells to γ-radiation results in several specific patterns of miRNA response. It appears that alteration in miRNA expression seen 4-24 hours after irradiation has no direct association with carcinogenesis. However, it is likely to affect other cell functions, such as DNA repair.

Medical Exposure to Radiation and Thyroid Cancer

In 2008, the worldwide estimated age-standardised incidence rates for thyroid cancer incidence were 4.7 and 1.5 per 100 000 women and men, respectively. Thyroid cancer’s overall contribution to the worldwide cancer burden is relatively small, but incidence rates have increased over the last three decades throughout the world. This trend has been hypothesised to reflect a combination of technological advances enabling increased detection, but also changes in environmental factors, including population exposure to ionising radiation from fallout, diagnostic tests and treatment for benign and malignant conditions. Studies of the atomic bomb survivors and populations treated with radiotherapy have established radiation as a risk factor for thyroid cancer, particularly from early life exposure. About 0.62 mSv (20%) of the global annual per caput effective radiation dose comes from diagnostic medical and dental radiation for the period of 1997–2007, increased from 0.4 mSv for the years 1991–1996. This international trend of increasing population exposure to medical diagnostic sources of radiation, attributed in large part to the growing use of computed tomography scans, but also interventional radiology procedures, has raised concerns about exposure to radiosensitive organs such as the thyroid. Worldwide, medical and dental X-rays constitute the most common type of diagnostic medical exposures, but their contribution to the cumulative effective dose is relatively low, whereas computed tomography scans account for 7.9% of diagnostic radiology examinations but 47% of the collective effective dose from diagnostic radiation procedures in parts of the world. Although the radiation exposure from computed tomography scans is substantially lower than that from radiotherapy, multiple computed tomography scans could result in non-trivial cumulative doses to the thyroid. Studies are currently underway to assess the incidence of cancer in large cohorts of children who received computed tomography scans. National and international efforts have been developed to raise awareness and to standardise procedures for use of computed tomography and interventional radiology procedures in paediatric and general populations.

Thyroidology and public health: The challenges ahead

Thyroidology and public health: The challenges ahead

The role of common variants of non-homologous end-joining repair genes XRCC4, LIG4 and Ku80 in thyroid cancer risk

Variations, such as single nucleotide polymorphisms (SNPs) in DNA damage repair genes have been pointed out as possible factors to cancer predisposition. Ionizing radiation (IR) induces DNA double strand breaks (DSBs) and is the main recognized risk factor for thyroid cancer. However, most of the patients do not show chronic contact with IR and the other factors have non-concordant data. Thus, thyroid cancer could be due to gene variations in association with certain exogenous factors. One of the pathways that repair DSBs is DNA non-homologous end-joining (NHEJ) that comprises several polymorphic genes. We intend to study the role of polymorphic variants in XRCC4, LIG4 and Ku80 genes, since there is scarcity of data on the role of these genes in thyroid cancer susceptibility. We carried out a hospital-based case-control study in a Caucasian Portuguese population (109 patients and 217 controls) to estimate the potential role of the XRCC4 (N298S and T134I), LIG4 (T9I) and Ku80 (Ex21-238Gright curved arrow A, Ex21+338Tright curved arrow C, Ex21-352Cright curved arrow A, Ex21+466Aright curved arrow G) polymorphisms in the individual susceptibility for this disease. The results here reported do not associate these polymorphisms with susceptibility for non-familial thyroid cancer. However, when the data were analyzed according to the type of tumour, significant results for Ku80 Ex21-238Gright curved arrow A and Ex21+466Aright curved arrow G were found for papillary tumours (adjusted OR = 2.281; 95% CI =; 1.063-4.894; P=0.034). Taken together these results suggest that some of these variants in NHEJ genes can contribute to thyroid cancer susceptibility. However, further studies with a larger sample size will be needed to support our results.

Risk Factors and a Predictive Model for Thyroid Cancer in Korean Women

Thyroid cancer incidence in Korean women has increased radically and is the highest in all cancer types. However, the rate of cancer screening among women is very low. The aim of the study was to determine the risk factors for thyroid cancer and to develop a predictive model based on these risk factors. The study design comprised a literature review and a case-control study. To construct a predictive model, the participants selected were 260 female outpatients diagnosed with malignant neoplasm of thyroid gland who had undergone thyroid removal surgery. A total of 259 people for the control group were selected by adopting a 5-year age-matching method. From the literature review, 6 categories of risk factors were identified. Nine variables, including occupation, live(d) in coastal region, family history of thyroid cancer, history of benign thyroid tumor, menopause status and weight gain, number of full-term deliveries, abortion, exercise intensity, and stress, remained as statistically significant risk factors in the stepwise regression model. Regarding the predictive power of the model, the area under the receiver operating characteristic curve was .79, accuracy was .77, sensitivity was .89, specificity was .65, positive predictive value was .72, and negative predictive value was .85. The predictive power of the model was relatively good, so it can be used to identify individuals at high risk for thyroid cancer. The predictive model can be used in promoting to participate in early cancer-screening tests. Thus, it will be possible to detect thyroid cancer in its earliest stage, diminish mortality, and improve quality of life.

88 Genetic polymorphisms in the MMP2 and MMP9 genes decreased lung cancer risk

The incidence of differentiated thyroid carcinoma (DTC) is increasing in most developed countries. The only well-known risk factor for thyroid cancer is exposure to ionising radiation. DTC is characterised by a strong hereditability, and individual susceptibility is likely due to genetic factors modulating the environmental risk. Identification of genetic polymorphisms is important for understanding the potential mechanisms involved in thyroid carcinogenesis. In this Review, we assess epidemiological data on the role of germ-line DNA polymorphisms and the risk of DTC. We have included only case–control studies that compare the incidence of germ-line mutations in patients with DTC, with the incidence of mutations in patients without a history of DTC. Such an analysis of genetic susceptibility in differentiated thyroid cancer has not yet been published.

Is ionizing radiation responsible for the increasing incidence of thyroid cancer?

The dose of exposure to ionizing radiation appears to correlate with increased risk of thyroid microcarcinoma. Can ionizing radiation be a factor contributing to the increasing incidence of thyroid cancer around the world?

Nonradiation Risk Factors for Thyroid Cancer in the US Radiologic Technologists Study

The incidence of thyroid cancer has been rapidly increasing in the United States, but few risk factors have been established. The authors prospectively examined the associations of self-reported medical history, anthropometric factors, and behavioral factors with thyroid cancer risk among 90,713 US radiologic technologists (69,506 women and 21,207 men) followed from 1983 through 2006. Incident thyroid cancers in 242 women and 40 men were reported. Elevated risks were observed for women with benign thyroid conditions (hazard ratio (HR) = 2.35, 95% confidence interval (CI): 1.73, 3.20), benign breast disease (HR = 1.56, 95% CI: 1.08, 2.26), asthma (HR = 1.68, 95% CI: 1.00, 2.83), and body mass index > or =35.0 versus 18.5-24.9 kg/m(2) (HR = 1.74, 95% CI: 1.03, 2.94; P-trend = 0.04). Current smoking was inversely associated with thyroid cancer risk (HR = 0.54). No clear associations emerged for reproductive factors, other medical conditions, alcohol intake, or physical activity. Despite few thyroid cancers in men, men with benign thyroid conditions had a significantly increased risk of thyroid cancer (HR = 4.65, 95% CI: 1.62, 13.34), and results for other risk factors were similar to those for women. Consistent with prior studies, obesity and benign thyroid conditions increased and current smoking decreased the risk of thyroid cancer. The novel findings for benign breast disease and asthma warrant further investigation.

Association of Polymorphisms in Genes of the Homologous Recombination DNA Repair Pathway and Thyroid Cancer Risk

Ionizing radiation exposure has been pointed out as a risk factor for thyroid cancer. The double-strand breaks induced by this carcinogen are usually repaired by homologous recombination repair pathway, a pathway that includes several polymorphic genes. Since there is a scarcity of data about the involvement of these gene polymorphisms in thyroid cancer susceptibility, we carried out a case-control study in a Caucasian Portuguese population. We genotyped 109 patients and 217 controls for the XRCC3 T241M, XRCC2 R188H, NBS1 E185Q, and RAD51 Ex1-59G>T polymorphisms to evaluate their potential main effects on risk for this pathology. The results obtained showed that for the RAD51 Ex1-59G>T polymorphism, the homozigosity for the variant allele was associated with an almost significant increase of the odds ratio (OR) (adjusted OR = 1.9; confidence interval 95%: 1.0-3.5; p = 0.057). Additionaly, when the XRCC3 T241M data were analyzed concerning the presence of at least one wild-type allele, we observed that individuals homozygous for the variant allele had a higher risk for thyroid cancer (adjusted OR = 2.0; confidence interval 95%: 1.1-3.6; p = 0.026). When the data were analyzed according to the number of RAD51 Ex1-59G>T and XRCC3 T241M variant alleles, the coexistence of three or more variant alleles in either gene was associated to a significant higher risk (three variant alleles: adjusted OR = 2.9, p = 0.036; four variant alleles: adjusted OR = 8.0, p = 0.006). Since XRCC3 is involved in the assembly and stabilization of RAD51 protein multimers at double-strand break sites, we cannot exclude that the interaction of both polymorphisms can lead to a decreased DNA repair capacity and consequently increased risk for thyroid cancer.

Mutations of the thyroglobulin gene and its relevance to thyroid disorders

To perform an update review on thyroglobulin gene mutations associated with congenital hypothyroidism, thyroid cancer, and autoimmunity. Forty-two thyroglobulin mutations have been identified in dyshormonogenetic congenital hypothyroidism. Clinical and laboratory criteria defining defective thyroglobulin synthesis are mostly related to thyroglobulin mutations, generally caused by intracellular thyroglobulin transport defects to the colloid rather than defects in thyroid hormones synthesis. Some mutated thyroglobulin may escape the rigorous chaperone control and reach the colloid, allowing a wide phenotypic spectrum that includes euthyroidism in an adequate iodine environment. In some patients, continuous levothyroxine treatment does not reduce elevated serum thyroid-stimulating hormone (TSH) levels that may lead to goiter development. Prenatally, inactive mutant thyroglobulin will not be able to synthesize thyroid hormones and may increase pituitary thyrotroph threshold for thyroid hormone feedback. Congenital goiter is a risk factor for thyroid cancer and some thyroglobulin variants may confer susceptibility to thyroid autoimmunity. Advances in the understanding of thyroglobulin genetic defects and its severity should allow researchers to perform adequate molecular diagnosis, genetic counseling, and intrauterine treatment to prevent subtle deficits in central nervous system development. This knowledge should improve the understanding of physiological functions of the thyroid and influence of nutritional iodine.

Germ-line DNA polymorphisms and susceptibility to differentiated thyroid cancer

The incidence of differentiated thyroid carcinoma (DTC) is increasing in most developed countries. The only well-known risk factor for thyroid cancer is exposure to ionising radiation. DTC is characterised by a strong hereditability, and individual susceptibility is likely due to genetic factors modulating the environmental risk. Identification of genetic polymorphisms is important for understanding the potential mechanisms involved in thyroid carcinogenesis. In this Review, we assess epidemiological data on the role of germ-line DNA polymorphisms and the risk of DTC. We have included only case-control studies that compare the incidence of germ-line mutations in patients with DTC, with the incidence of mutations in patients without a history of DTC. Such an analysis of genetic susceptibility in differentiated thyroid cancer has not yet been published.