Occupational radiation exposure and thyroid cancer incidence in a cohort of U.S. radiologic technologists, 1983-2013.

Although childhood exposure to ionizing radiation is a well-established risk factor for thyroid cancer, the risk associated with adulthood exposure remains unclear. We prospectively examined the association between cumulative, low-to-moderate dose occupational radiation exposure to the thyroid and thyroid cancer incidence in the U.S. Radiologic Technologists cohort. The study included 89,897 members who completed at least two of four mailed questionnaires and were cancer-free at the time of the first questionnaire. Cumulative occupational thyroid radiation dose (mean = 57 mGy, range = 0-1,600 mGy) was estimated based on self-reported work histories, historical data and, during the years 1960-1997, 783,000 individual film badge measurements. During follow-up, we identified 476 thyroid cancer cases. We used Poisson regression to estimate excess relative risk of thyroid cancer per 100 milliGray (ERR/100 mGy) absorbed dose to the thyroid gland. After adjusting for attained age, sex, birth year, body mass index and pack-years smoked, we found no association between thyroid dose and thyroid cancer risk (ERR/100 mGy = -0.05, 95% CI <-0.10, 0.34). In this large cohort study of radiologic technologists, protracted, low-to-moderate dose ionizing radiation exposure to the thyroid gland in adulthood was not associated with an increased risk of thyroid cancer.

The rising trend of papillary carcinoma in thyroidectomies: 14-years of experience in a referral center of Turkey.

BACKGROUND: During the past 25 years, the incidence of thyroid papillary carcinoma (TPC), especially the micropapillary subtype, has been increasing in different countries worldwide. The rise in the rate of thyroid malignancies were also determined in Turkey in the last two decades. This fact was attributed to the Chernobyl accident because Turkey is one of the affected countries by the radioactive fallout. The aim of this study was to assess the changes in the parameters of the thyroid and put forth the reasons in a 14-year period. METHODS: The patient records, demographic and malignancy characteristics, and operations of 1,585 patients who had a thyroidectomy from 1996 to 2009 were reviewed retrospectively. The study was divided in two equal time periods for comparison of data. RESULTS: A total of 216 thyroid carcinomas (13.6%) were diagnosed in the study period. There was a significant increase in the frequency of papillary (P <0.023) and micropapillary (P <0.001) carcinomas when the two different time periods were compared. The rate of follicular, medullary and other types of malignancies did not change. In the second period (2003 to 2009) of analysis, the rate of micropapillary carcinoma (P = 0.001) and within male (P = 0.031) and female (P <0.001) genders, application of total thyroidectomy (p = 0.029), and multicentric disease (P = 0.015) increased significantly. A slight decrease in the mean age of the whole number of patients and patients with papillary and micropapillary carcinomas (P >0.05) was observed. The increased number of TPC >10 mm was insignificant. Geographic region and age specific malignancy increase was not determined. CONCLUSIONS: Micropapillary carcinoma has become a dominant type of thyroid malignancy in Turkey. The main reasons of this transition were mandatory iodization and much higher application of total thyroidectomy in surgery. Improvement in healthcare and diagnostic techniques are the complementary factors. Due to its lack of molecular and genetic basis from the perspective of thyroid cancer, the Chernobyl disaster has lost its importance in Turkey.

Molecular and genetic markers of follicular-cell thyroid cancer: etiology and diagnostic and therapeutic opportunities.

Thyroid cancer has an increasing incidence in the US population and worldwide, with 95% of the cancers being of follicular cell origin-papillary, follicular, or anaplastic thyroid carcinomas. Both follicular and papillary thyroid cancers portend good survival rates, with estimated 5-year survival amongst differentiated thyroid cancer approaching 97%. On the other hand, the median survival for a patient with anaplastic thyroid carcinoma is measured in months. Despite the optimistic survival rates for papillary and follicular thyroid carcinoma, a subset of this population demonstrates resistance to radioactive iodine, and a proclivity for more aggressive tumors with higher rates of recurrence and metastasis.As there is an increased understanding of the molecular etiology of thyroid cancer, there is also a new interest in alternative treatment methods for those nonresponsive to typical treatment. Multiple signaling pathways have been identified, including the mitogen activated protein kinase pathway, as crucial to thyroid tumor formation and progression. Additionally, particular oncogenes have been identified as prevalent in anaplastic thyroid carcinoma and thought to be involved in the transformation from differentiated to anaplastic histology.We review the current literature and evidence describing the molecular and genetic etiology of non-medullary (follicular cell derived) thyroid carcinomas including papillary, follicular, and anaplastic thyroid carcinoma. Additionally, we evaluate the current literature on emerging and established therapies of molecular and genetic targets in these cancers.

Risk Factors for Recurrence of Follicular Thyroid Cancer: A Systematic Review.

Background: In risk assessment of recurrence, papillary thyroid cancer (PTC) and follicular thyroid cancer (FTC) are often grouped together as differentiated thyroid cancer (DTC). However, while risk factors affecting recurrence of PTC are well established, risk factors for recurrence of FTC are not. This systematic review examines risk factors for recurrence of FTC and evaluates their significance. Methods: A systematic search on PubMed and Embase was performed in September 2020, including studies evaluating risk factors for recurrence of FTC. A quality assessment of the enrolled studies was performed. Results: Nine studies (n = 1544 patients) from eight countries were included. The average recurrence rate was 13.6%, and distant metastasis (DM) constituted 64.8% of the recurrent cases. The risk factors examined were sex, age at diagnosis, primary tumor size, degree of invasiveness, focality, positive resection margin, lymph node (LN) metastasis, and DM at diagnosis. Risk factors correlated with recurrence of FTC were age older than 45 years, primary tumor size above 40 mm, widespread invasion, multifocality, positive resection margin, LN metastasis, and DM at diagnosis. Sex was not a statistically significant risk factor. Conclusions: We identified seven risk factors associated with recurrence of FTC. Age and multifocality were found to be of greater impact regarding recurrence risk of FTC compared with PTC. Future research needs to address the impact of different risk factors for recurrence of FTC particularly including age, primary tumor size, angioinvasion, and mutational status.

The occurrence of malignant thyroid lesions in patients after radioiodine treatment due to benign thyroid diseases.

INTRODUCTION: Radioiodine treatment (RT) of benign thyroid diseases is a well-known, safe, and effective treatment. In a group of patients after RT, who remained in long-term follow-up, sporadic cases of malignant thyroid lesions occurred. The aim of the study was to estimate how often it happened despite the exclusion of malignancy before RT. MATERIAL AND METHOD: A group of 4314 patients (7438 person-years) underwent RT and subsequently were followed-up for 1-8 years (mean 20.69 months). Apart from thyroid function estimation, if needed, fine needle aspiration biopsy (FNAB) of the thyroid or neck focal lesions was performed based on ultrasonographic or clinical examination. Patients with pathological FNAB were analyzed and histopathologically verified. RESULTS: In 12 out of 4314 cases (0.27%) suspicious FNAB results were found. Suspicious thyroid lesion results were found in 9 patients (8 F, 1 M), aged 46-73 (average 56 years) followed up for 3-57 months after RT: papillary cancer in two patients, Hürthle cell tumour in one patient, and suspicious cells in two patients (with benign lesions on postoperative histopathology). Two patients refused surgery (a suspicion of papillary cancer in one case and suspicious cells in FNAB in the second case). A follicular tumour in FNAB was suspected in two cases (no data about the first, and the second with lung cancer was not operable). In the remaining 3 cases FNAB revealed lymph node metastases due to other cancers. CONCLUSIONS: Malignant thyroid lesions in patients after RT due to benign thyroid diseases are seldom detected. However, periodical clinical and ultrasonographic evaluation is recommended.

Papillary and Follicular Thyroid Cancer in children and adolescents: Current approach and future directions.

An increasing number of children are diagnosed with differentiated thyroid cancer. With an excellent prognosis for the majority of pediatric patients, the goal of therapy is to optimize outcome while reducing complications. Increased knowledge of the somatic, oncogenic driver mutations provides opportunities to improve the accuracy of diagnosis, to stratify surgery, and to treat patients with morbidly invasive or refractory disease. Treatment complications can be reduced by referral to regional, high-volume pediatric thyroid centers.

Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study.

Second primary neoplasms (SPNs) are a recognised late effect of treatment for childhood cancer. Thyroid SPNs can develop after exposure to low-dose radiation, due to the radio-sensitivity of the thyroid gland. The British Childhood Cancer Survivor Study (BCCSS) was set up to directly monitor the late effects of treatment, including risk of SPNs, in childhood cancer survivors and includes 17,980 5-year survivors. We carried out a cohort analysis to determine the risk of thyroid SPNs in the BCCSS, and estimated risk using standardised incidence ratios (SIRs), relative risk (RR) using multivariate Poisson regression and cumulative incidence curves. There were 340,202 person years at risk subsequent to a 5-year survival, median follow-up 17.4 years per survivor. We identified 50 thyroid SPNs including 31 (62%) papillary carcinomas, 15 (30%) follicular carcinomas and 4 (8%) other types. 88% of thyroid SPNs developed after exposure to radiotherapy in or around the thyroid gland. SIR overall was 18.0 (95% confidence interval 13.4-23.8). Risk of thyroid cancer was highest after Hodgkin's disease: RR 3.3 (1.1-10.1) and Non Hodgkin's Lymphoma: RR 3.4 (1.1-10.7) relative to leukaemia (RR 1.0) (p < 0.001). Survivors treated with radiotherapy in childhood had a RR of 4.6 (1.4-15.1) relative to survivors not treated with radiotherapy (RR 1.0), p = 0003. In conclusion, the risk of thyroid cancer in childhood cancer survivors is relatively high in this cohort of childhood cancer survivors. These results will be of use in counselling survivors of childhood cancer exposed to radiation in or around the thyroid area.

Follow-up and results in patients with differentiated thyroid carcinoma in Castilla-La Mancha (2001-2015). The CADIT-CAM study. / Resultados del seguimiento de pacientes con carcinoma diferenciado de tiroides en Castilla-La Mancha (2001-2015). Estudio CADIT-CAM.

OBJECTIVE: The CADIT-CAM study was designed to retrospectively analyze the clinical characteristics, treatments, and outcomes of patients with differentiated thyroid carcinoma (DTC) in Castilla La Mancha. PATIENTS AND METHODS: A total of 1434 patients from 7 hospitals in Castilla La Mancha were enrolled into the study from 2001 to 2015. RESULTS: Seventy-seven percent of patients were female, with a mean age at diagnosis of 48 years. Papillary thyroid carcinoma accounted for 93% of cases. Mean tumor size was significantly smaller at final follow-up (P<.05). Radioiodine ablation (RA) was performed in 84% of patients, and its use decreased during the study, especially in tumors with low recurrence risk. Recurrence occurred in 22% of patients and was associated to male gender, greater tumor size, multifocality, lymph node metastases, extrathyroid involvement, distant metastases and increasing thyroglobulin antibody titers. At the end of follow-up 76.2% of patients were alive and free of disease, 2.4% had died from DTC. Overall survival of the cohort was 95.1% at 15 years of follow-up. CONCLUSIONS: Characteristics of DTC in this Spanish cohort are similar to those reported in other studies in our country. Final results were excellent and use of treatment (RA) was consistent with risk-stratified recommendations.

Glycemic index, glycemic load and thyroid cancer risk.

BACKGROUND: Risk of thyroid cancer has already been related to refined cereals and starch food, but the association has not been studied in terms of glycemic index (GI) and glycemic load (GL). PATIENTS AND METHODS: We analyzed data from a case-control study conducted in Italy from 1986 to 1992 and including 399 histologically confirmed and incident cases of thyroid cancer and 616 control subjects. Information on dietary habits was derived through a food-frequency questionnaire and multivariate odds ratios (ORs) for GI and GL levels were estimated with adjustment for age, education, sex, area of residence, history of diabetes, body mass index, smoking, alcohol consumption, intake of fruit and vegetables, and noncarbohydrate energy intake. RESULTS: Compared with the lowest tertile, the ORs in subsequent tertiles were 1.68 and 1.73 for GI, and 1.76 and 2.17 for GL. The OR for highest tertile of GI compared with lowest one was 1.70 for papillary and 1.57 for follicular thyroid cancer. The ORs for GL were 2.17 for papillary and 3.33 for follicular thyroid cancer. CONCLUSION: Our study shows that high dietary levels of GI and GL are associated with thyroid cancer risk.

Menstrual and reproductive factors in the risk of thyroid cancer in Japanese women: the Japan Public Health Center-Based Prospective Study.

The aim of this study was to evaluate the associations between menstrual and reproductive factors and thyroid cancer risk among Japanese women. A total 54 776 women aged 40-69 years completed a self-administered questionnaire, which included menstrual and reproductive history. During 1990-2012, 187 newly diagnosed cases of thyroid cancer were identified. Hazard ratios (HRs) and 95% confidence intervals (CIs) for menstrual and reproductive factors and incidence of thyroid cancer were estimated using Cox proportional hazards regression. Postmenopausal women who had natural menopause were at reduced risk of thyroid cancer than premenopausal women in the age-area-adjusted model (HR: 0.62 per 1 year increase, 95% CI: 0.39-0.99), but this association was slightly attenuated and no longer statistically significant in the multivariable-adjusted model. On analysis by menopausal status, an inverse association between age at menarche and risk of thyroid cancer was observed for premenopausal women (HR: 0.83 per 1 year increase, 95% CI: 0.70-0.98, P trend=0.03), but not for postmenopausal women. The risk of thyroid cancer increased with surgical menopause compared with natural menopause (HR: 2.34, 95% CI: 1.43-3.84). Although increasing age at menopause and duration of fertility were associated with an increased risk of thyroid cancer, this association was not observed among postmenopausal women. This study confirmed that early age at menarche for premenopausal women and surgical menopause and late age at natural menopause for postmenopausal women were associated with the development of thyroid cancer. Our results support the hypothesis that exposure to estrogens increases the risk of thyroid cancer.

Differentiated thyroid carcinomas associated with chronic thyroiditis: biological and clinical properties.

AIM: To determine biological and clinical features of papillary and follicular thyroid carcinomas associated or not associated with chronic thyroiditis. MATERIALS AND METHODS: The study was conducted by retrospective analysis of medical histories of 2,459 patients with thyroid cancer. Tumor size, its category according to the TNM system, multi-focal properties of tumor growth, carcinoma invasiveness, as well as disease stage, rates of relapses and metastasis, and also cumulative survival rates were analyzed. RESULTS: The tumor size in patients with papillary or follicular carcinoma associated with thyroiditis was smaller compared to the patients without thyroiditis. In the first case, the invasion frequency into extrathyroid structure and into the capsule was also lower. Multi-focal growth of both carcinoma types was registered more frequently in the presence of thyroiditis. The frequency of papillary carcinoma metastasis to lateral cervical lymph nodes was lower in the presence of thyroiditis, the frequency being equal for metastasis into lymph nodes of the VI lymph outflow zone in both groups of patients (with and without thyroiditis). In the presence of thyroiditis, the frequency of distant papillary carcinoma metastasis was decreased, no metastases were detected in patients with follicular carcinoma. In the group of patients with papillary carcinoma there was found no relation between the presence of thyroiditis and disease stage, relapse rates, and mortality levels; however, the risk of follicular carcinoma relapse was significantly lower in patients with thyroiditis. CONCLUSIONS: The presence of chronic thyroiditis in papillary carcinoma patients showed a certain positive impact on the course of the disease, in particular, primary tumor growth, invasion, and metastasis. Such effect is even more expressed in the patients with follicular thyroid carcinoma.

Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

BACKGROUND: The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk. METHODS: After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas. RESULTS: The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk. CONCLUSION: Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk.

Alcohol drinking, tobacco smoking, and anthropometric characteristics as risk factors for thyroid cancer: a countrywide case-control study in New Caledonia.

Exceptionally high incidence rates of thyroid cancer are observed in New Caledonia, particularly in Melanesian women. To investigate further the etiology of thyroid cancer and to clarify the reasons of this elevated incidence, the authors conducted a countrywide population-based case-control study in this multiethnic population. The study included 332 cases with histologically verified papillary or follicular carcinoma (293 women and 39 men) diagnosed in 1993-1999 and 412 population controls (354 women and 58 men) frequency matched by gender and 5-year age group. Thyroid cancer was negatively associated with tobacco smoking and alcohol drinking, but no inverse dose-response relation was observed. Height was positively associated with thyroid cancer, particularly in men. Strong positive associations with weight and body mass index were observed in Melanesian women aged 50 years or more, with an odds ratio of 5.5 (95% confidence interval: 1.5, 20.3) for a body mass index of 35 kg/m2 or greater compared with normal-weight women, and there was a clear dose-response trend. This study clarifies the role of overweight for thyroid cancer in postmenopausal women. Because of the high prevalence of obesity among Melanesian women of New Caledonia, this finding may explain in part the exceptionally elevated incidence of thyroid cancer in this group.

Relevance of iodine intake as a reputed predisposing factor for thyroid cancer.

UNLABELLED: Iodine is a trace element that is essential for the synthesis of thyroid hormone. Both chronic iodine deficiency and iodine excess have been associated with hypertrophy and hyperplasia of follicular cells, attributed to excessive secretion of TSH. This may be associated to thyroid cancer risk, particularly in women. Experimental studies have documented thyroid cancer induction by elevation of endogenous TSH, although in a small number of animals. Iodine deficiency associated with carcinogenic agents and chemical mutagens will result in a higher incidence of thyroid malignancy. Inadequate low iodine intake will result in increased TSH stimulation, increased thyroid cell responsiveness to TSH, increased thyroid cell EGF-induced proliferation, decreased TGFbeta 1 production and increased angiogenesis, all phenomena related to promotion of tumor growth. Epidemiological studies associating iodine intake and thyroid cancer led to controversial and conflicting results. There is no doubt that introduction of universal iodine prophylaxis in population previously in chronic iodine-deficiency leads to a changing pattern of more prevalent papillary thyroid cancer and declining of follicular thyroid cancer. Also anaplastic thyroid cancer is practically not seen after years of iodine supplementation. Iodine excess has also been indicated as a possible nutritional factor in the prevalence of differentiated thyroid cancer in Iceland, Hawaii and, more recently, in China. IN CONCLUSION: available evidence from animal experiments, epidemiological studies and iodine prophylaxis has demonstrated a shift towards a rise in papillary carcinoma, but no clear relationship between overall thyroid cancer incidence and iodine intake.

[Epidemiology of thyroid tumors: effect of environmental iodine intake].

The incidence of thyroid cancer has been reported to be 0.5-1.3%, when assessed by sonographic examination and 3.7-28.4% by histologic examination at autopsies. These incidences are much higher than those of clinically evident thyroid cancer, which are 2.0/100,000 for males and 7.2/100,000 for females, reported in Japan. In iodine deficient areas, chronic stimulation by TSH causes multinodular autonomous growth and function, leading to hyperthyroidism in middle-aged and elderly subjects. Incidence of Plummer's disease among Japanese with sufficient iodine intake is very low, accounting for 0.5-0.8% of all thyroid nodules and 0.3% of all thyrotoxic patients. The Plummer/Graves ratio was higher than 1 in endemic goiter area before iodine supplementation. Iodine intake affects the type of thyroid carcinoma. Decreased intake of iodine is associated with higher frequency of follicular and anaplastic cancers and lower frequency of papillary cancer. The high prevalence of papillary cancer(>85%) with good prognosis may explain the preferred selection of partial rather than total thyroidectomy in Japan.

Risk of malignancy in thyroid nodules classified as TIR-3A: What therapy?

BACKGROUND: The aim of the present study was to assess the clinical applicability of the TIR3A category in managing thyroid nodules, to examine the malignancy rates of TIR 3A and TIR 3B nodules, and to suggest management guidelines for these nodules. MATERIALS AND METHODS: Thyroid cytologies performed in patients referred to our Department between January 2014 and August 2016 were classified according to the guidelines published by the SIAPEC. 102 cases were included in this retrospective study and were divided into two groups: 19 TIR3A were included in group A and 83 TIR3B in group B. RESULTS: In group A, malignancy was diagnosed in 4 (21.1%) cases, papillary thyroid cancer was found in 3 patients and follicular thyroid cancer in 1; one case was classified as microcarcinoma, in two cancer was multicentric and bilateral and in one central node metastases were observed. In Group B malignancy was diagnosed in 48 (57.8%) patients, papillary thyroid cancer was found in 36 patients and follicular cancer in 12; microcarcinoma was observed in 25 cases, 12 were unilateral multicentric and 7 bilateral multicentric; in 3 cases central node metastases were present. CONCLUSION: Thyroid nodules with TIR3A cytology have a lower risk of malignancy than TIR3B cases, for which the new SIAPEC classification has proved accurate and effective. Malignancy rates in nodules with TIR3A cytology are higher than expected, although the real and accurate definition of the risk is extremely difficult. The recommendation to perform an accurate follow-up and repeat the fine-needle aspiration still appears the best option. For better management of patients with TIR3A cytology a careful assessment of risk factors and ultrasound characteristics is always needed. Further multicenter studies with longer follow-up are needed to better define the efficacy of this classification, the actual cancer risk, and the best management of these lesions.

Clinical case seminar: metastatic follicular thyroid carcinoma arising from congenital goiter as a result of a novel splice donor site mutation in the thyroglobulin gene.

CONTEXT: Defects in thyroglobulin (Tg) synthesis are one of the causes of thyroid dyshormonogenesis. Only a few mutations in the Tg gene have been described. OBJECTIVES: We describe a novel Tg gene mutation and discuss the mechanisms by which it causes dyshormonogenesis with subsequent malignant transformation. CASES: Two siblings aged 21 and 19 yr presented with recurrent goiters for which they had undergone multiple thyroid surgeries since early childhood. The older sibling was diagnosed with metastatic follicular thyroid carcinoma at age 15 yr. METHODS: The entire coding region and intron-exon boundaries of the Tg gene were amplified and sequenced from the patients. We also sequenced the boundaries of exon 5 and intron 5 from both parents. RT-PCR amplification of a cDNA fragment encompassing exons 4-6 was also performed. RESULTS: A homozygous G to A point mutation at position +1 of the splice donor site of intron 5 (g.IVS5+1G-->A) was detected in both patients, whereas a monoallelic mutation was found in their parents. RT-PCR amplification of a cDNA fragment covering exons 4-6 revealed a 191-bp fragment in the patients and 351- and 191-bp fragments in the parents. Sequence analysis of these two fragments confirmed deletion of exon 5 in the 191-bp fragment. CONCLUSIONS: Aberrant splicing occurred as a result of the g.IVS5+1G-->A mutation, which caused fusion of exons 4 and 6, resulting in the frame shift at codon position 141 and a premature stop codon at position 147 (FS141-->147X). The malignant transformation is likely a result of prolonged TSH stimulation.

Medical diagnostic x rays and thyroid cancer.

BACKGROUND: Diagnostic x rays are the largest man-made source of exposure to ionizing radiation for the general population. Whether there are meaningful cancer risks associated with such exposures is unclear. Most previous case-control studies have relied on recalled histories of x rays, and there is concern that completeness and accuracy of recall might differ between cancer case and control subjects. PURPOSE: The present study used information recorded prospectively in hospital charts to address the relationship between medical diagnostic x rays and risk of thyroid cancer. METHODS: The Swedish Cancer Registry and the Uppsala-Orebro Regional Cancer Registry were used to identify persons with papillary or follicular thyroid cancer diagnosed from January 1, 1980, through December 31, 1992, among residents of the Uppsala Health Care Region. After histopathologic review, there were 484 such case subjects available for study. An equal number of age-, sex-, and county of residence-matched control subjects from the general population were randomly selected on the basis of the Swedish Registry of the Total Population. Lifetime residential histories were compiled, and radiology records were searched at all Swedish hospital serving regions where study subjects ever maintained an official residence. Approximate radiation doses to the thyroid gland for specific types of x-ray examinations were assigned on the basis of mean values of measurements made in Sweden in 1973-1975 and in the United States in 1970. Odds ratios were used to evaluate the association between diagnostic radiography and risk of thyroid cancer. RESULTS: A total of 3853 medical diagnostic x rays were ascertained among thyroid cancer case subjects and 4039 among the matched control subjects. There were no tendency for case subjects to have had more of the types of x-ray procedure associated with higher radiation dose to the thyroid gland (i.e., those involving the head or neck area). This finding was true even when analysis was restricted to x rays occurring before 1960, when doses likely were higher than in more recent years, and for examinations occurring in childhood and adolescence, when susceptibility to radiation-induced thyroid cancer is greatest. The relative risk of thyroid cancer was not significantly associated with estimated cumulative dose to the thyroid gland from diagnostic x rays (two-sided P for trend = .80). CONCLUSION: These data indicate that the risk of thyroid cancer due to medical diagnostic x rays, if any, is very small.