Risk Factor For Thyroid Cancer Research Articles

Iodine intake as a risk factor for thyroid cancer: a comprehensive review of animal and human studies.

Thyroid cancer (TC) is the most common endocrine malignancy and in most countries, incidence rates are increasing. Although differences in population iodine intake are a determinant of benign thyroid disorders, the role of iodine intake in TC remains uncertain. We review the evidence linking iodine intake and TC from animal studies, ecological studies of iodine intake and differentiated and undifferentiated TC, iodine intake and mortality from TC and occult TC at autopsy, as well as the case–control and cohort studies of TC and intake of seafood and milk products. We perform a new meta-analysis of pooled measures of effect from case–control studies of total iodine intake and TC. Finally, we examine the post-Chernobyl studies linking iodine status and risk of TC after radiation exposure. The available evidence suggests iodine deficiency is a risk factor for TC, particularly for follicular TC and possibly, for anaplastic TC. This conclusion is based on: a) consistent data showing an increase in TC (mainly follicular) in iodine deficient animals; b) a plausible mechanism (chronic TSH stimulation induced by iodine deficiency); c) consistent data from before and after studies of iodine prophylaxis showing a decrease in follicular TC and anaplastic TC; d) the indirect association between changes in iodine intake and TC mortality in the decade from 2000 to 2010; e) the autopsy studies of occult TC showing higher microcarcinoma rates with lower iodine intakes; and f) the case control studies suggesting lower risk of TC with higher total iodine intakes.Electronic supplementary materialThe online version of this article (doi:10.1186/s13044-015-0020-8) contains supplementary material, which is available to authorized users.

Abstract #1075: Documentation of Thyroid Cancer Risk Factors in Patients with Thyroid Nodules

Abstract #1075: Documentation of Thyroid Cancer Risk Factors in Patients with Thyroid Nodules

Thyroid Volume and Its Relation to Anthropometric Measures in a Healthy Cuban Population

Objectives: The aim of this study was to describe the thyroid volume in healthy adults by ultrasound and to correlate this volume with some anthropometric measures and other differentiated thyroid cancer risk factors. Study Design: Thyroid volume and anthropometric measures were recorded in a sample of 100 healthy adults, including 21 men and 79 women aged 18-50 years, living in a non-iodine-deficient area of Havana city. Results: The average thyroid volume was 6.6 ± 0.26 ml; it was higher in men (7.3 ml) than in women (6.4 ml; p = 0.15). In the univariate analysis, thyroid volume was correlated with all anthropometric measures, but in the multivariate analysis, body surface area was found to be the only significant anthropometric parameter. Thyroid volume was also higher in current or former smokers and in persons with blood group AB or B. Conclusion: Specific reference values of thyroid volume as a function of body surface area could be used for evaluating thyroid volume in clinical practice. The relation between body surface area and thyroid volume is coherent with what is known about the relation of thyroid volume to thyroid cancer risk, but the same is not true about the relation between thyroid volume and smoking habit.

Effect of age on the sensitivity of the rat thyroid gland to ionizing radiation.

Exposure to ionizing radiation during childhood is a well-known risk factor for thyroid cancer. Our study evaluated the effect of age on the radiosensitivity of rat thyroid glands. Four-week-old (4W), 7 -week-old (7W), and 8-month-old (8M) male Wistar rats were exposed to 8 Gy of whole-body X-ray irradiation. Thyroids were removed 3–72 h after irradiation, and non-irradiated thyroids served as controls. Ki67-positivity and p53 binding protein 1 (53BP1) focus formation (a DNA damage response) were evaluated via immunohistochemistry. Amounts of proteins involved in DNA damage response (p53, p53 phosphorylated at serine 15, p21), apoptosis (cleaved caspase-3), and autophagy (LC3, p62) were determined via western blotting. mRNA levels of 84 key autophagy-related genes were quantified using polymerase chain reaction arrays. Ki67-positive cells in 4W (with high proliferative activity) and 7W thyroids significantly decreased in number post-irradiation. The number of 53BP1 foci and amount of p53 phosphorylated at serine 15 increased 3 h after irradiation, regardless of age. No increase in apoptosis or in the levels of p53, p21 or cleaved caspase-3 was detected for any ages. Levels of LC3-II and p62 increased in irradiated 4W but not 8M thyroids, whereas expression of several autophagy-related genes was higher in 4W than 8M irradiated thyroids. Irradiation increased the expression of genes encoding pro-apoptotic proteins in both 4W and 8M thyroids. In summary, no apoptosis or p53 accumulation was noted, despite the expression of some pro-apoptotic genes in immature and adult thyroids. Irradiation induced autophagy in immature, but not in adult, rat thyroids.

Detection rate and its time trend analysis on thyroid cancer from 2009 to 2013 in Shaoxing, Zhejiang Province

Objective To analyze the detection rate of thyroid cancer from 2009 to 2013 in Shaoxing of Zhejiang province and its time trend. Methods The data of thyroid cancer in Shaoxing from 2009 to 2013 was collected to calculate the detection rate, age adjusted detection rate and percentage change of incidence, and the annual percentage change(APC)of incidence was estimated by linear regression based on the logarithm of the incidence rates observed. Results During 2009-2013, a total of 3 290 new cases were diagnosed as thyroid cancer with the sex ratio of male to female being 1∶3.69. The detection rate of thyroid cancer was 14.98/100 000(male 6.39/100 000, female 23.59/100 000), with age-standardized detection rate by Chinese standard population(ASR China)9.13/100 000(male 3.94/100 000, female 14.31/100 000), and age-standardized detection rate by world standard population(ASR world)10.39/100 000(male 4.47/100 000, female 16.32/100 000). The detection rate of thyroid cancer increased from 7.26/100 000 in 2009 to 27.26/100 000(APC=39.65%, P<0.05), with the detection rate among males increasing from 2.42/100 000 to 12.65/100 000(APC=48.44%, P<0.05), and the detection rate among female increasing from 12.15/100 000 to 41.96/100 000(APC=37.58%, P<0.05). In Shaoxing, most of the new thyroid cancer cases were from 25 to 59 years old, and the highest incidence happened in the group of 50-54 years. For each age group, the detection rate in female was almost over two-folds higher than the incidence in male. Conclusion The detection rate of thyroid cancer was increased year by year from 2009 to 2013 in Shaoxing, especially among the young and middle-aged women. The corresponding measures must be taken to control the risk factors of thyroid cancer. (Chin J Endocrinol Metab, 2015, 31: 4-9) Key words: Thyroid cancer; Detection rate; Time trend

Thyroid cancer has become a problem that gravely impacts public health

The global incidence of thyroid cancer has been increasing in recent years, but the reasons for the increase are still not well established. Widely applied and improved diagnostic modalities, together with that people are more likely to concern their health status may contribute to the increased incidence of thyroid microcarcinomas and incidental (asymptomatic)carcinomas. There might be an association between Hashimoto thyroiditis and thyroid cancer. Many environmental factors, such as exposure to ionizing radiation, may also be risk factors for thyroid cancer. (Chin J Endocrinol Metab, 2015, 31: 1-3) Key words: Thyroid cancer; Incidence; Epidemiology

Reproductive Factors but Not Hormonal Factors Associated with Thyroid Cancer Risk: A Systematic Review and Meta-Analysis

Many studies have investigated the association between hormonal and reproductive factors and thyroid cancer risk but provided contradictory and inconclusive findings. This review was aimed at precisely estimating this association by pooling all available epidemiological studies. 25 independent studies were retrieved after a comprehensive literature search in databases of PubMed and Embase. Overall, common hormonal factors including oral contraceptive and hormone replacement therapy did not alter the risk of thyroid cancer. Older age at menopause was associated with weakly increased risk of thyroid cancer in overall analysis (RR = 1.24, 95% CI 1.00–1.53, P = 0.049); however, longer duration of breast feeding was related to moderately reduced risk of thyroid cancer, suggested by pooled analysis in all cohort studies (RR = 0.7, 95% CI 0.51–0.95, P = 0.021). The pooled RR in hospital-based case-control studies implicated that parous women were more susceptible to thyroid cancer than nulliparous women (RR = 2.30, 95% CI 1.31–4.04, P = 0.004). The present meta-analysis suggests that older age at menopause and parity are risk factors for thyroid cancer, while longer duration of breast feeding plays a protective role against this cancer. Nevertheless, more relevant epidemiological studies are warranted to investigate roles of hormonal and reproductive factors in thyroid carcinogenesis.

Sustained Lower Incidence of Thyroid Cancer in West Cumbria, UK

Background: In recent years, incidences of thyroid cancer have increased in developed countries; one of the known risk factors for thyroid cancer is exposure to radioiodine. Previous research by Bowlt and Tiplady [5] has shown an inverse link between radioactive iodine levels contained in thyroid tissue of deceased inhabitants and the distance they lived from the Sellafield nuclear facility in Cumbria, UK. Objectives: The present study aimed to determine what thyroid cancer incidences were in the regional localities in Cumbria for the last decade. Methods: An ethics-approved retrospective cohort study in which age-standardised incidence of thyroid cancer per 100,000 population was compared between localities within Cumbria and with UK average figures. Conclusions: The present study shows that the apparent lower incidence of thyroid cancer in West Cumbria has persisted, although due to the limited number of thyroid cancers diagnosed, a statistically significant difference was not observed. Further research – potentially involving populations living near sources of radioiodine emission - is indicated to investigate if there are any mechanisms that underlie this apparent trend.

Ultrasound and cytological diagnostics of thyroid - its proper application in case of coexisting disturbing clinical signs and symptoms, suggestive of active proliferative lesion

Ultrasound and cytological diagnostics of thyroid - its proper application in case of coexisting disturbing clinical signs and symptoms, suggestive of active proliferative lesion

Thyroid Cancer and Radiation

Epidemiological studies have reported an increasing incidence of thyroid cancer worldwide. This phenomenon is unclear whether it is apparent increase or true increase. In Korea, the incidence rate of thyroid cancer in both men and women showed abrupt increase from 1999 through 2011. The possible reason of this increase is suggested as improved screening with sensitive diagnostic procedures. If the incidence increase is real, there are risk factors such as ionizing radiation, obesity, diabetes mellitus, genetic predisposition, hormones, iodine diet, Hashimoto's thyroiditis, and pollutants contributing to this increased incidence. Exposure to ionizing radiation is a well-known risk factor for thyroid cancer. This was verified by epidemiological studies from survivors after Hiroshima and Nagasaki and the Chernobyl accident. The studies demonstrated that the dose-response relationship seems to be linear. However, a statistically significant increase has hardly been described with exposure to low dose radiation (<100 mSv). In addition, with respect to the data on adult exposure, there was no proven radiation related increase of the thyroid cancer incidence. Therefore, a clear understanding for the pathogenesis of radiation induced thyroid cancer is essential. Like other cancers, there are several gene alterations thought to be involved in pathogenesis of sporadic thyroid cancer. Whereas, the exact pathogenesis of radiation induced thyroid cancer by genetic alteration has not been demonstrated until now. Recently, gene expression profiling by microarray analysis has been applied to investigate the possible pathogenesis.

Research of DNA repair genes polymorphism XRCC1 and XPD and the risks of thyroid cancer development in persons exposed to ionizing radiation after Chornobyl disaster

The objective of this work was to determine and compare the features of DNA repair gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms in patients with thyroid cancer (TC), who were exposed to ionizing radiation (IR) as a result of the Chornobyl disaster, and in patients without exposure to ionizing radiation in history. Determination of gene XRCC1 Arg399Gln and XPD Lys751Gln polymorphisms was performed by polymerase chain reaction (PCR) in 102 patients with thyroid cancer: 38 people, who were exposed to ionizing radiation due to Chornobyl disaster (members of the accident, and evacuees and residents from controlled areas contaminated with radionuclides), 64 individuals without exposure to ionizing radiation in history and 41 persons residents of Ukraine without cancer pathology in the control group. For comparison of the data on spontaneous and radiation-associated thyroid cancer and settlement of allele frequencies differences and risk of cancer pathology were used the literature data on control groups of populations of Russia, Belarus and Poland. Comparing to the literature data on XRCC1 Arg399Gln polymorphisms in radiation-exposed individuals without cancer pathology, the risk of thyroid cancer in homozygous minor allele XRCC1 Gln399Gln carriers, who were exposed to ionizing radiation was significantly increased: OR = 4,14, p = 0,001 (CI95 % 1,72-9,93). In homozygous carriers of the minor allele of the gene XPD Lys751Gln, exposed to IR, revealed increased risk of thyroid cancer: OR = 3,30, p = 0,05 (CI 95 % 0,82-14,14), when compared with the control group of Ukrainian population. The carriage of homozygous minor allele Gln399Gln XRCC1 and XPD Gln751Gln of DNA repair genes is a risk factor for thyroid cancer under the influence of ionizing radiation in research group of Ukrainian population.

Cold Climate Is a Risk Factor for Thyroid Cancer.

The incidence rates of differentiated thyroid cancers of all sizes increased between 1988 and 2005 in both men and women. Exposure to ionizing radiation is the best-established environmental risk factor for thyroid cancer. Nonionizing radiation from cell phones has also been implicated. A positive correlation between all-cancer incidence rates and latitude and an inverse correlation between all-cancer incidence rates and temperature have been reported. In the present study, we examined the relationship between thyroid cancer incidence and average temperature in 50 U.S. states. The age-adjusted incidence of thyroid cancer is from U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2010, Incidence and Mortality Web-based Report (Atlanta: Department of Health and Human Services, Centers for Disease Control and Prevention and National Cancer Institute; 2013, available at: www.cdc.gov/uscs). Average temperature by state is from the National Climatic Data Center, National Oceanic and Atmospheric Administration (http://www.ncdc.noaa.gov). Information on high-impact exposure to nuclear radiation by state is from the National Radiation Exposure Screening and Education Program, U.S. Health Resources and Services Administration (http://www.hrsa.gov/gethealthcare/conditions/radiationexposure). Cell-phone subscriber data for 2007 is from the Governing State and Local Sourcebook (http://sourcebook.governing.com). Mean elevation and latitude of U.S. states is from "Elevations and Distances in the United States," Reston, VA: U.S. Geological Survey, April 29, 2005 (http://pubs.er.usgs.gov). There was a significant negative correlation between average temperature by state and the age-adjusted incidence of all thyroid cancers (r2 = -0.212, P = 0.001). Because of the possible effects of ionizing radiation exposure from nuclear testing and nonionizing radiation exposure from cell phones, multiple linear regression analysis was performed. The analysis was done only for all thyroid cancers and for thyroid cancers in whites. The data from blacks and Hispanics were too fragmentary to analyze. In all thyroid cancers and thyroid cancers in whites, there was a significant negative correlation between average temperature and incidence that was unrelated to nuclear testing, cell-phone use, altitude, and latitude and was independent of the significant correlation of cell-phone subscriptions per population with thyroid cancer in whites. Living in a cold-climate state, such as Alaska, doubles the risk of thyroid cancer as compared with a warm state such as Texas. Because of climate change, a significantly raised risk of heat-related and cold-related mortality is expected in the years to come. The elderly will be most at risk. No doubt, incidence patterns of thyroid cancer and other cancers may be affected.

Associations between body mass and papillary thyroid cancer stage and tumor size: a population-based study.

The incidence of large thyroid tumors has increased over the past decades, suggesting that improved diagnosis is not the only driver of increased thyroid cancer incidence. Obesity has recently been implicated as an independent risk factor for thyroid cancer in specific populations. We aimed to investigate whether thyroid tumor size and advanced stage of diagnosis is associated with the obesity epidemic, for the first time, in a US population-based cohort. We leveraged existing data and linked 1,077 papillary thyroid cancer patients from the Nevada Central Cancer Registry to the Department of Motor Vehicle dataset. Tumor size and cancer stage were assessed from cancer registry records, and obesity was obtained using height and weight in the Department of Motor Vehicle records and measured by a body mass index greater than 25 kg/m(2). Crude analysis showed obesity as was associated with tumors larger than 2 cm [odds ratio (OR) 1.50, p = 0.0423] and advanced cancer stage (stage III and IV) (OR 1.40, p = 0.0111). After adjusting for confounders, a significant association was still observed between obesity and tumor larger than 2 cm (OR 1.53, p = 0.0339). A marginally significant association was shown between obesity and advanced cancer stage (OR 1.29, p = 0.0649). As thyroid cancer incidence continues to increase, this study's finding that obesity was significantly associated with larger tumor size and marginally significantly associated with advanced tumor stage can help establish new preventative actions and identify new target populations for interventions.

Thyroid nodules: pathophysiological insight on oncogenesis and novel diagnostic techniques.

Thyroid nodules are a very frequent pathology among common population. Despite the vast majority of them are of benign origin, the incidence of thyroid cancer is currently rather rising. Although there are several risk factors of thyroid cancer and several clinical, ultrasound, biochemical and molecular diagnostic markers, the exact mechanisms of thyroid oncogenesis and the linkage between thyroid nodule ultrasound appearance and its biological character remain unclear. While ionizing radiation is the only one well-known risk factor for thyroid cancer, the significance of some others remains unclear. The aim of our review was to discuss some not completely known pathophysiological mechanisms involved in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell proliferation, thyroid autoimmunity and pregnancy and to describe pathophysiological background of some ultrasound markers of thyroid cancer (size, echogenicity, vascularization, calcifications and stiffness). Better knowledge in this field is crucial for development of novel diagnostic techniques and therapeutic approaches. For example, the analysis of BRAF, RAS and other mutations in cytological samples may help to distinction between follicular thyroid carcinoma and follicular thyroid adenoma and may significantly decrease the number of unnecessary surgery among patients with thyroid nodules. Alternatively, the different malign cells growth, angiogenesis, destructions of thyroid follicles, reparative changes, growth retardation, fibrosis and increased interstitial fluid pressure implicate the typical ultrasound appearance of papillary thyroid cancer (hypoechogenicity, irregular vascularization, microcalcifications, stiffness) which is essential to catch the suspicious nodules on the basis of their ultrasound appearance among large amount of benign nodules.

Incidence and mortality of thyroid cancer in six cancer registries of Zhejiang province, 2000-2009

To investigate the incidence and mortality rates of thyroid cancer in Zhejiang province during 2000 to 2009. The data of thyroid cancer were collected from six cancer registries in Zhejiang province and the incidence and mortality rates of thyroid cancer were analysed. The mean annual incidence rate of thyroid cancer in Zhejiang cancer registration areas was 6.93/100 000 during 2000 to 2009, and male/female ratio was 1: 3.43. The incidence rate was 3.62/100 000 in 2000 and it increased to 11.42/100 000 in 2009, with the annual percent change (APC) of 16.32% (95% confidence interval: 12.90%-19.85%). The mean annual mortality rate of thyroid cancer was 0.27/100 000 during 2000 to 2009, and male/female ratio was 1: 1.12. The mortality showed a rising trend without a distinct fluctuation from 2000 to 2009, the APC was 2.14% (95% confidence interval: from -7.10% to 12.30%). The incidence showed a rising trend with the increase of ages after 15 years old, and peaked at 55-60 years old. The mortality was low before 54 years old, but showed a rising trend with a distinct fluctuation after 55 years old, and peaked at 85-90 years old. The prevention and control of risk factors for thyroid cancer in young and middle-aged people is key to decrease the incidence and mortality of thyroid cancer.

Assessment of Risk Factors For Patients With Thyroid Cancer in Mosul Teaching Hospitals

Background and Objectives: Thyroid cancer is the most common endocrine malignancy. Several riskfactors were found to play a role in thyroid cancer. The aim of the study was to identify risk factors forthyroid cancer in Mosul city and to assess the relationship between some types of food and thyroidcancer.Materials and Methods: The Non-experimental Quantitative design (a Case – Control approach) wasused in this study. The study was conducted at AL-Jamhori Teaching Hospital, Al-Salam TeachingHospital, and Nuclear Medicine and Oncology Hospital in Mosul city. The period from 18th. October,2012 to 20th, August, 2013. A formal consent was taken from all participants (case group and controlgroup) in questionnaire . A non probability purposive sample was selected that consisted (172) clientsdivided into two groups, a case group (86) clients with thyroid cancer and a control group (86) clientswithout goiter and thyroid cancer.Results: According to the age, the highest percentage was in the age group (50-59 years),constituted(34%)for the case group. The majority of the case group are female who were accounted (78.0%) femaleto male ratio 4:1. The incidence of differentiated thyroid carcinoma according to histopathology wasincreased for women compared with men specially papillary thyroid carcinoma.Conclusion: The statistical analysis shows that there are significant relationship in previous history forgoiter, family history for thyroid cancer, and exposure to radio active iodine items with respect to the riskfactors of thyroid cancer.Keywords: Assessment, Risk Factors, Thyroid Cancer.

Ultrasound risk factors of thyroid cancer

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Risk-Based Ultrasound Screening for Thyroid Cancer in Obese Patients is Cost-Effective

A higher body mass index (BMI) is associated with more advanced stages of thyroid cancer. Screening obese patients for thyroid cancer has been proposed but has yet to be examined for cost-effectiveness. The objective of this study was to assess the cost-effectiveness of ultrasound (US) screening of obese patients for thyroid cancer. A decision-tree model compared cost savings for the following: (i) base case scenario of an obese patient with thyroid nodule found by palpation, (ii) universal US screening of all obese patients, and (iii) risk-based US screening in obese patients. Risk-based screening consisted of patients who had at least one of four major identified risk factors for thyroid cancer (family history of thyroid cancer, radiation exposure, Hashimoto's thyroiditis, and/or elevated thyrotropin). Patients with nodules underwent established treatment and management guidelines. The model accounted for recurrence, complications, and long-term treatment/follow-up for five years. Outcome probabilities were identified from a literature review. Costs were estimated using a third-party payer perspective. Sensitivity analyses were performed to examine the impact of risk factor prevalence and US cost on the model. The resulted costs per patient were $210.73 in the base case scenario, $434.10 in the universal US screening arm, and $166.72 in the risk-based screening arm. Risk-based screening remained cost-effective until more than 14% of obese patients had risk factors and with a wide variation of US costs ($0-$1113). Risk-based US screening in selected obese patients with risk factors for thyroid cancer is cost-effective. Recommendations for screening this subgroup will result in cost savings and a likely decreased morbidity and mortality in this subpopulation with more aggressive disease.

Predictors for Thyroid Carcinoma in Israel: A National Cohort of 1,624,310 Adolescents Followed for up to 40 Years

Data on adolescent precursors of thyroid cancer in adulthood are scant. In order to evaluate potential risk factors for thyroid cancer, we linked two national data sources: the military recruitment health examinations and the Israel National Cancer Register. The study population (1,624,310 participants) included 1,145,865 Jewish males aged 16-19 years when examined between 1967 and 2005, and 478,445 Jewish females aged 16-19 years when examined between 1989 and 2005. The cancer follow-up extended up to 2006. Multivariable Cox proportional hazards modeling was used. During 24,389,502 person years of follow-up, 760 incidence cases of thyroid cancer were identified. The mean age at diagnosis was 25.2±4.2 years for women and 37.2±10.0 years for men. Women had a substantially higher incidence (birth cohort-adjusted hazard ratio (HR)=5.70 [95% CI 4.45-7.31]; p<0.001). Height predicted incidence in both sexes, with birth cohort-adjusted HRs of 1.03 (p<0.001) in males and 1.04 (p<0.001) in females, per 1 cm increment in height. In males, but not in females, there was a graded association between education, as measured by years of schooling, and incidence of thyroid cancer. Body mass index was not associated with incidence. In a multivariable analysis of 617,613 males and 469,185 females examined from 1989 onwards, which included sex, birth year, height, and education, the excess risk in females persisted strongly (HR=5.67 [CI 4.30-7.13]), as did the association with height. Female sex, measured height in adolescence, and later birth cohorts were independent predictors of thyroid cancer in young and middle-aged adults in Israel. Further study is needed to unravel the mechanisms whereby height is associated with thyroid cancer.

Variants in the ATM‐CHEK2‐BRCA1 axis determine genetic predisposition and clinical presentation of papillary thyroid carcinoma

The risk of developing papillary thyroid carcinoma (PTC), the most frequent form of thyroid malignancy, is elevated up to 8.6-fold in first-degree relatives of PTC patients. The familial risk could be explained by high-penetrance mutations in yet unidentified genes, or polygenic action of low-penetrance alleles. Since the DNA-damaging exposure to ionizing radiation is a known risk factor for thyroid cancer, polymorphisms in DNA repair genes are likely to affect this risk. In a search for low-penetrance susceptibility alleles we employed Sequenom technology to genotype deleterious polymorphisms in ATM, CHEK2, and BRCA1 in 1,781 PTC patients and 2,081 healthy controls. As a result of the study, we identified CHEK2 rs17879961 (OR = 2.2, P = 2.37e-10) and BRCA1 rs16941 (odds ratio [OR] = 1.16, P = 0.005) as risk alleles for PTC. The ATM rs1801516 variant modifies the risk associated with the BRCA1 variant by 0.78 (P = 0.02). Both the ATM and BRCA1 variants modify the impact of male gender on clinical variables: T status (P = 0.007), N status (P = 0.05), and stage (P = 0.035). Our findings implicate an important role of variants in the ATM- CHEK2- BRCA1 axis in modification of the genetic predisposition to PTC and its clinical manifestations.