Immune-related conditions and subsequent risk of brain cancer in a cohort of 4.5 million male US veterans.

BACKGROUND: Case-control studies have reported an inverse association between self-reported history of allergy and risk of glioma, but cohort data are limited. Our objectives were to evaluate the associations of major groups of medically diagnosed immune-related conditions (allergy/atopy, autoimmune disease, diabetes, infectious/inflammatory disease) and to explore associations with specific conditions in relation to subsequent diagnosis of brain cancer in a large cohort study. METHODS: We used hospital discharge records for a cohort of 4.5 million male US veterans, of whom 4383 developed primary brain cancer. Rate ratios (RRs) and 95% confidence intervals (CIs) were calculated using time-dependent Poisson regression. RESULTS: We found a significant trend of decreasing RRs for brain cancer with longer duration of allergy/atopy (P=0.02), but not for other conditions studied. Rate ratios of brain cancer for allergy/atopy and diabetes with duration of 10 or more years were 0.60 (95% CI: 0.43, 0.83) and 0.75 (95% CI: 0.62, 0.93), respectively. Several associations with specific conditions were found, but these did not withstand correction for multiple comparisons. CONCLUSIONS: This study lends some support to an inverse association between allergy/atopy and diabetes of long duration and brain cancer risk, but prospective studies with biological samples are needed to uncover the underlying biological mechanisms.

Cigarette smoking, alcohol intake, and risk of glioma in the NIH-AARP Diet and Health Study.

BACKGROUND: Although cigarette smoking and alcohol drinking increase the risk of several cancers and certain components of cigarette smoke and alcohol can penetrate the blood-brain barrier, it remains unclear whether these exposures influence the risk of glioma. METHODS: We examined the associations between cigarette smoking, alcohol intake, and risk of glioma in the National Institutes of Health-AARP Diet and Health Study, a prospective study of 477,095 US men and women ages 50-71 years at baseline. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using models with age as the time metric and adjusted for sex, race/ethnicity, education, and marital status. RESULTS: During a median 10.5 person-years of follow-up, 492 men and 212 women were diagnosed with first primary glioma. Among men, current, heavier smoking was associated with a reduced risk of glioma compared with never smoking, but this was based on only nine cases. No associations were observed between smoking behaviours and glioma risk in women. Greater alcohol consumption was associated with a decreased risk of glioma, particularly among men (>2 drinks per day vs <1 drink per week: HR=0.67, 95% CI=0.51-0.90). CONCLUSION: Smoking and alcohol drinking do not appear to increase the risk of glioma.

Mobile phone use and glioma risk: comparison of epidemiological study results with incidence trends in the United States.

OBJECTIVE: In view of mobile phone exposure being classified as a possible human carcinogen by the International Agency for Research on Cancer (IARC), we determined the compatibility of two recent reports of glioma risk (forming the basis of the IARC's classification) with observed incidence trends in the United States. DESIGN: Comparison of observed rates with projected rates of glioma incidence for 1997-2008. We estimated projected rates by combining relative risks reported in the 2010 Interphone study and a 2011 Swedish study by Hardell and colleagues with rates adjusted for age, registry, and sex; data for mobile phone use; and various latency periods. SETTING: US population based data for glioma incidence in 1992-2008, from 12 registries in the Surveillance, Epidemiology, and End Results (SEER) programme (Atlanta, Detroit, Los Angeles, San Francisco, San Jose-Monterey, Seattle, rural Georgia, Connecticut, Hawaii, Iowa, New Mexico, and Utah). PARTICIPANTS: Data for 24,813 non-Hispanic white people diagnosed with glioma at age 18 years or older. RESULTS: Age specific incidence rates of glioma remained generally constant in 1992-2008 (-0.02% change per year, 95% confidence interval -0.28% to 0.25%), a period coinciding with a substantial increase in mobile phone use from close to 0% to almost 100% of the US population. If phone use was associated with glioma risk, we expected glioma incidence rates to be higher than those observed, even with a latency period of 10 years and low relative risks (1.5). Based on relative risks of glioma by tumour latency and cumulative hours of phone use in the Swedish study, predicted rates should have been at least 40% higher than observed rates in 2008. However, predicted glioma rates based on the small proportion of highly exposed people in the Interphone study could be consistent with the observed data. Results remained valid if we used either non-regular users or low users of mobile phones as the baseline category, and if we constrained relative risks to be more than 1. CONCLUSIONS: Raised risks of glioma with mobile phone use, as reported by one (Swedish) study forming the basis of the IARC's re-evaluation of mobile phone exposure, are not consistent with observed incidence trends in US population data, although the US data could be consistent with the modest excess risks in the Interphone study.

Single-nucleotide polymorphisms in selected cytokine genes and risk of adult glioma.

A role of immunological factors in glioma etiology is suggested by reports of an inverse relationship with history of allergy or autoimmune disease. To test whether single-nucleotide polymorphisms (SNPs) in cytokine genes were related to risk of adult glioma, we genotyped 11 SNPs in seven cytokine genes within a hospital-based study conducted by the National Cancer Institute and an independent, population-based study by the National Institute for Occupational Safety and Health (overall 756 cases and 1190 controls with blood samples). The IL4 (rs2243248, -1098T>G) and IL6 (rs1800795, -174G>C) polymorphisms were significantly associated with risk of glioma in the pooled analysis (P trend = 0.006 and 0.04, respectively), although these became attenuated after controlling for the false discovery rate (P trend = 0.07 and 0.22, respectively). Our results underscore the importance of pooled analyses in genetic association studies and suggest that SNPs in cytokine genes may influence susceptibility to glioma.

Season of birth and risk of brain tumors in adults.

BACKGROUND: Recent studies demonstrated an excess of winter births in children with brain tumors and in adults with various neurologic or psychiatric diseases relative to the general population. OBJECTIVE: To investigate a possible association between month of birth and risk of brain tumors in adults using data from a large, hospital-based case-control study. METHODS: Cases were patients with incident glioma (n = 489) or meningioma (n = 197) diagnosed at hospitals in Boston, MA, Phoenix, AZ, and Pittsburgh, PA. Controls (n = 799) were patients hospitalized for a variety of nonmalignant conditions and frequency matched to cases by hospital, age, sex, race/ethnicity, and distance of residence from hospital. Odds ratios (ORs) were calculated using multivariate unconditional logistic regression allowing for cyclic variation in risk with month of birth. RESULTS: A relationship between month of birth and risk of adult glioma and meningioma was found, best described by a 12-month periodic function with peaks in February and January and troughs in August and July. The association between month of birth and risk of glioma differed significantly by handedness, with left-handed and ambidextrous subjects born during late fall through early spring being at particularly high risk of adult glioma as compared with those born at other times of the year. CONCLUSION: These findings suggest the importance of seasonally varying exposures during the pre- or postnatal period in the development of brain tumors in adults.

Occupation and the risk of adult glioma in the United States.

OBJECTIVE: Previous studies have observed increased glioma incidence associated with employment in the petroleum and electrical industries, and in farming. Several other occupations have also been associated with increased risk, but with inconsistent results. We evaluated associations between occupational title and glioma incidence in adults. METHODS: Cases were 489 patients with glioma diagnosed from 1994 to 1998 at three United States hospitals. Controls were 799 patients admitted to the same hospitals for non-malignant conditions. An experienced industrial hygienist grouped occupations that were expected to have similar tasks and exposures. The risk of adult glioma was evaluated for those subjects who ever worked in an occupational group for at least six months, those who worked longer than five years in the occupation, and those with more than ten years latency since starting work in the occupation. RESULTS: Several occupational groups were associated with increased glioma incidence for having ever worked in the occupation, including butchers and meat cutters (odds ratio [OR] = 2.4; 95% confidence limits [CL]: 1.0, 6.0), computer programmers and analysts (OR = 2.0; 95% CL: 1.0, 3.8), electricians (OR = 1.8; 95% CL: 0.8, 4.1), general farmers and farmworkers (OR = 2.5; 95% CL: 1.4, 4.7), inspectors, checkers, examiners, graders, and testers (OR = 1.5; 95% CL: 0.8, 2.7), investigators, examiners, adjustors, and appraisers (OR = 1.7; 95% CL: 0.8, 3.7), physicians and physician assistants (OR = 2.4; 95% CL: 0.8, 7.2), and store managers (OR = 1.6; 95% CL: 0.8, 3.1), whereas occupation as a childcare worker was associated with decreased glioma incidence (OR = 0.4; 95% CL: 0.2, 0.9). These associations generally persisted when the subjects worked longer than five years in the occupation, and for those with more than ten years latency since starting to work in the occupation. CONCLUSIONS: This is our first analysis of occupation and will guide future exposure-specific assessments.

Gliomas presenting after age 10 in individuals with neurofibromatosis type 1 (NF1).

Children with neurofibromatosis 1 (NF1) often develop low-grade gliomas, but brain tumors are infrequently encountered in adults with NF1. The authors present evidence from two clinical series, one including patients known to have NF1 and another focusing on adults with new onset brain tumors, that suggests an association between NF1 and symptomatic gliomas in older individuals. They also summarize the clinical data on 17 adolescents or adults with NF1 and symptomatic gliomas. The findings suggest that individuals with NF1 are at increased risk of developing gliomas throughout their lives.

Prevalence of antimicrobial resistance in Salmonellae isolated from market-age swine.

Antimicrobial resistance levels were examined for 365 Salmonella isolates recovered from the lymph nodes (n = 224) and cecal contents (n = 141) of market-age swine at slaughter. Antimicrobial resistance testing was performed by disk diffusion using 13 antibiotics common in the treatment of disease in human and veterinary medicine. Although none of the antibiotics tested were used subtherapeutically within the last 5 years on the farms sampled, resistance to chlortetracycline, penicillin G, streptomycin, and sulfisoxazole was common. Penicillin G resistance was significantly more frequent (P = 0.03) and sulfisoxazole resistance was significantly less frequent (P < 0.01) in lymph node versus cecal isolates. Multidrug resistance was observed among 94.7% of the lymph node isolates and 93.5% of the cecal isolates. The most frequent multidrug resistance pattern included three antibiotics-penicillin G, streptomycin, and chlortetracycline. Isolates in somatic serogroup B, and more specifically, Salmonella Agona and Salmonella Schwarzengrund isolates, were often resistant to a greater number of antibiotics than were isolates in the other serogroups. Streptomycin, sulfisoxazole, ampicillin (lymph node isolates), and nitrofurantoin (cecal isolates) resistance levels differed significantly between somatic serogroups. The prevalence of penicillin G-, streptomycin-, and sulfisoxazole-resistant isolates differed significantly between serovars for both lymph node and cecal isolates. Results of this study suggest that a correlation exists between the somatic serogroup or serovar of a Salmonella isolate and its antimicrobial resistance status, which is specific to the antibiotic of interest and the source of the isolate (lymph node versus cecal contents).

Diagnostic radiation and the risk of multiple myeloma (United States).

OBJECTIVE: To evaluate the relationship between cumulative lifetime exposure to diagnostic radiation and the risk of multiple myeloma using data from a large, multi-center, population-based case-control study. METHODS: Study subjects included a total of 540 cases with newly diagnosed multiple myeloma and 1998 frequency-matched population controls living in three areas of the United States (Georgia, Michigan, New Jersey). Information on exposure to diagnostic X-rays was obtained by personal interview. RESULTS: No association was found between case-control status and the total number of reported diagnostic X-rays of any type (odds ratio (OR) for 20 or more compared to less than 5 X-rays = 0.9, 95% confidence interval (95% CI) = 0.7-1.2). There was no evidence of an excess risk of multiple myeloma among individuals who reported exposure to 10 or more diagnostic X-rays that impart a relatively high radiation dose to the bone marrow, as compared to individuals reporting no such exposures (OR 0.7, 95% CI 0.4-1.3). CONCLUSIONS: These data suggest that exposure to diagnostic X-rays has a negligible impact, if any, on risk of developing multiple myeloma.

Thyroid cancer after radiotherapy for childhood cancer.

The thyroid gland in children is among the most sensitive organs to the carcinogenic effects of ionizing radiation, and very young children are at especially high risk. Risk associated with exposure to external X- or gamma-radiation increases linearly with increasing dose to the thyroid gland at low-to-moderate doses, but the dose-response relationship appears to flatten at the very high doses characteristic of cancer radiotherapy. Because of the extreme sensitivity of the thyroid gland in children, there is a risk of radiation-induced thyroid cancer even when the thyroid gland is outside of the irradiated field. Increased incidence of thyroid cancer has been noted following radiotherapy for childhood Hodgkin disease, non-Hodgkin lymphoma, neuroblastoma, Wilms tumor, acute lymphocytic leukemia and tumors of the central nervous system. Radiation-induced tumors begin to appear 5-10 years after irradiation and excess risk persists for decades, perhaps for the remainder of life. The background incidence of thyroid cancer is two- to threefold higher among females than males, and the absolute increase in risk due to irradiation is higher in females as well. Most of the thyroid cancers that occur in association with irradiation are of the papillary type, for which the cure rate is high if tumors are detected early. This highlights the importance of long-term surveillance of persons irradiated during childhood. Important areas for research include the possibility that children with certain types of first cancer are especially susceptible, the basis of the greater female susceptibility, the joint effects of radiation and other factors, and genetic mechanisms in radiation-induced and spontaneously occurring thyroid cancer.

Cellular-telephone use and brain tumors.

BACKGROUND: Concern has arisen that the use of hand-held cellular telephones might cause brain tumors. If such a risk does exist, the matter would be of considerable public health importance, given the rapid increase worldwide in the use of these devices. METHODS: We examined the use of cellular telephones in a case-control study of intracranial tumors of the nervous system conducted between 1994 and 1998. We enrolled 782 patients through hospitals in Phoenix, Arizona; Boston; and Pittsburgh; 489 had histologically confirmed glioma, 197 had meningioma, and 96 had acoustic neuroma. The 799 controls were patients admitted to the same hospitals as the patients with brain tumors for a variety of nonmalignant conditions. RESULTS: As compared with never, or very rarely, having used a cellular telephone, the relative risks associated with a cumulative use of a cellular telephone for more than 100 hours were 0.9 for glioma (95 percent confidence interval, 0.5 to 1.6), 0.7 for meningioma (95 percent confidence interval, 0.3 to 1.7), 1.4 for acoustic neuroma (95 percent confidence interval, 0.6 to 3.5), and 1.0 for all types of tumors combined (95 percent confidence interval, 0.6 to 1.5). There was no evidence that the risks were higher among persons who used cellular telephones for 60 or more minutes per day or regularly for five or more years. Tumors did not occur disproportionately often on the side of head on which the telephone was typically used. CONCLUSIONS: These data do not support the hypothesis that the recent use of hand-held cellular telephones causes brain tumors, but they are not sufficient to evaluate the risks among long-term, heavy users and for potentially long induction periods.

A preliminary survey of antibiotic resistance of Salmonella in market-age swine.

We conducted an epidemiological survey of antibiotic resistance in Salmonella recovered from market-age swine at five different Texas farms. These farms, which were visited between October 1997 and June 1998, were completely integrated, farrow-to-finish operations. Samples were taken from the lymph nodes and cecal contents at the time of slaughter. The Salmonella samples that were recovered were sent to the National Veterinary Services Laboratory for serotyping. Antibiotic resistance was determined using the Dispens-O-Disc Susceptibility Test System using 13 different antimicrobial agents that have been utilized in either veterinary medicine, human medicine, or both. Preliminary analysis of the first 183 samples out of approximately 400 Salmonella samples recovered indicated that 183 (100%) of the Salmonella samples were resistant to penicillin G, and 122 (66.7%) were resistent to chlortetracycline. Six (3.3%) were resistant to four antibiotics (chlortetracycline, penicillin G, streptomycin, and sulfisoxazole), and 25 (13.7%) were resistant to three antibiotics (chlortetracycline, penicillin G, and either streptomycin, sulfisoxazole, or ampicillin). Variation was seen between serotypes, with four out of five S. agona samples (80.0%) and two out of eight S. derby samples (25.0%) resistant to four antibiotics. Variation in antibiotic resistance also was seen between farms. There is an increasing concern about the prevalent usage of antibiotics in medicine and agriculture and the relationship this may have on emerging microbial resistance patterns; therefore, continued surveillance on antibiotic resistance in animal production is warranted.

Thyroid palpation versus high-resolution thyroid ultrasonography in the detection of nodules.

Detection of thyroid nodules by physical examination and high-resolution ultrasonography was compared using small groups of blinded, experienced physician examiners working with a sample of 2441 persons from Estonia, most of whom were Chernobyl nuclear reactor clean-up workers. A random subsample of 113 (5%) persons was subjected to triple control examinations with both physical examination and high-resolution ultrasonography. Positive high-resolution ultrasonographic findings were considerably more reproducible among different observers than were positive physical examination findings. Agreement between methods was poor. Nodules were found in 169 (6.9%) subjects by physical examination and in 249 (10.2%) subjects by high-resolution ultrasonography. Physical examination found only 53 (21%) of the 249 nodules found by high-resolution ultrasonography. High-resolution ultrasonography did not confirm the existence of 115 (68%) of the 169 nodules found by physical examination. Only 6.4% of nodules less than 0.5 cm in diameter, as based on high-resolution ultrasonographic results, were detected by physical examination. Physical examination detection improved with increasing nodule size but was still only 48.2% for nodules larger than 2 cm. Physical examination was relatively effective in detecting nodules in the isthmus of the thyroid gland but much less so for nodules in the upper pole of the gland. Clinical evaluation and epidemiologic studies of nodular thyroid disease stand to benefit from the greater sensitivity and specificity of ultrasonographic examinations.

Do recorded doses overestimate true doses received by Chernobyl cleanup workers? Results of cytogenetic analyses of Estonian workers by fluorescence in situ hybridization.

Studies of workers who were sent to Chernobyl after the 1986 reactor accident are being conducted to provide a better understanding of the effects of chronic low-dose radiation exposures. A crucial component to these investigations is an accurate assessment of the radiation doses received during the cleanup activities. To provide information on biological measurements of dose, fluorescence in situ hybridization (FISH) with whole-chromosome painting probes has been applied to quantify stable chromosome aberrations (translocations and insertions) among a defined cohort of 4,833 cleanup workers from Estonia. Cytogenetic analysis of 48-h lymphocyte cultures from 118 Estonian cleanup workers (10.3 cGy mean recorded dose; 25 cGy maximum), 29 Estonian population controls and 21 American controls was conducted by three laboratories. More than 258,000 painted metaphases were evaluated. Overall, we observed lower translocation frequencies than has been reported in previous studies using FISH among Chernobyl cleanup workers. In our data, a clear association with increased levels of translocations was seen with increasing age at blood drawing. There was no correlation, however, between aberration frequency and recorded measurements of physical dose or any category of potential high-dose and high-dose-rate exposure such as being sent to Chernobyl in 1986, working on the roof near the damaged nuclear reactor, working in special zones or having multiple tours. In fact, the translocation frequency was lower among the exposed workers than the controls, though not significantly so. To estimate the level of effect that would have been expected in a population of men having an average dose of approximately 10 cGy, blood from six donors was exposed to low-LET radiation, and more than 32,000 metaphases were scored to estimate dose-response coefficients for radiation-induced translocations in chromosome pairs 1, 2 and 4. Based on these results, we estimate that had this group of 118 men received an average whole-body dose of 10-11 cGy, as chronic or acute exposures, an increase in the mean frequency of chromosome translocations of more than 40-65% would have been observed in their lymphocytes compared to findings in nonirradiated controls. In spite of evaluating more than a quarter of a million metaphases, we were unable to detect any increase in the mean, median or range in chromosome aberrations in lymphocyte cultures from a group of Estonian men who took part in the cleanup of the Chernobyl nuclear power site and those who did not. We conclude that it is likely that recorded doses for these cleanup workers overestimate their average bone marrow doses, perhaps substantially. These results are consistent with several negative studies of cancer incidence in Chernobyl cleanup workers and, if borne out, suggest that future studies may not be sufficiently powerful to detect increases in leukemia or cancer, much less distinguish differences between the effects of chronic compared to brief radiation exposures.

Incidence of intracranial tumors following hospitalization for head injuries (Denmark).

The incidence of brain and other intracranial tumors following head trauma was evaluated in a cohort of 228,055 Danish residents hospitalized because of concussion, fractured skull, or other head injury between 1977 and 1992 and followed for an average of eight years (maximum, 17 years). Traffic accidents, falls, and sports-related incidents were the usual causes of the injury. Malignant and benign neoplasms were identified by linking the study roster with records of the Danish Cancer Registry for the years 1977 to 1993. This approach precludes differential reporting of injuries by study participants as an explanation for any associations seen. Intracranial tumors of the nervous system occurred more often than expected based on incidence rates for the Danish population; however, most of the excess occurred during the first year after the injury and likely was due to the detection of tumors that were present before the injury occurred. Excluding the first year of follow-up, the standardized incidence ratio (SIR) was 1.15 (95 percent confidence interval [CI] = 0.99-1.32). The same general temporal pattern was seen for the major subtypes of brain tumor as for all types combined. SIRs after the first year were 1.0 for glioma (CI = 0.8-1.2), 1.2 for meningioma (CI = 0.8-1.7), and 0.8 for neurilemmoma (CI = 0.4-1.7). However, hemangioblastoma and hemangioma were more frequent than expected, based on 15 cases (SIR = 2.6, CI = 1.4-4.2). Results indicate that head trauma causes, at most, a small increase in the overall risk of brain tumors during the ensuing 15 years; however, a possible association with intracranial vascular tumors warrants further evaluation.

The Estonian study of Chernobyl cleanup workers: I. Design and questionnaire data.

Nearly 2% of the male population of Estonia aged 20-39 years were sent to Chernobyl to assist in the cleanup activities after the reactor accident. A cohort of 4,833 cleanup workers was assembled based on multiple and independent sources of information. Information obtained from 3,704 responses to a detailed questionnaire indicated that 63% of the workers were sent to Chernobyl in 1986; 54% were of Estonian and 35% of Russian ethnicity; 72% were married, and 1,164 of their 5,392 children were conceived after the Chernobyl disaster. The workers were less educated than their counterparts in the general population of Estonia, and only 8.5% had attended university. Based on doses entered in worker records, the mean dose was 11 cGy, with only 1.4% over 25 cGy. Nearly 85% of the workers were sent as part of military training activities, and more than half spent in excess of 3 months in the Chernobyl area. Thirty-six percent of the workers reported having worked within the immediate vicinity of the accident site; 11.5% worked on the roofs near the damaged reactor, clearing the highly radioactive debris. The most commonly performed task was the removal and burial of topsoil (55% of the workers). Potassium iodide was given to over 18% of the men. The study design also incorporates biological indicators of exposure based on the glycophorin A mutational assay of red blood cells and chromosome translocation analyses of lymphocytes; record linkage with national cancer registry and mortality registry files to determine cancer incidence and cause-specific mortality; thyroid screening examinations with ultrasound and fine-needle biopsy; and cryopreserved white blood cells and plasma for future molecular studies. Comprehensive studies of Chernobyl cleanup workers have potential to provide new information about cancer risks due to protracted exposures to ionizing radiation.

The Estonian study of Chernobyl cleanup workers: II. Incidence of cancer and mortality.

A cohort of 4,742 men from Estonia who had participated in the cleanup activities in the Chernobyl area sometime between 1986 and 1991 and were followed through 1993 was analyzed with respect to the incidence of cancer and mortality. Incidence and mortality in the cleanup workers were assessed relative to national rates. No increases were found in all cancers (25 incident cases compared to 26.5 expected) or in leukemia (no cases observed, 1.0 expected). Incidence did not differ statistically significantly from expectation for any individual cancer site or type, though lung cancer and non-Hodgkin's lymphoma both occurred slightly more often than expected. A total of 144 deaths were observed [standardized mortality ratio (SMR) = 0.98; 95% confidence interval (CI) = 0.82-1.14] during an average of 6.5 years of follow-up. Twenty-eight deaths (19.4%) were suicides (SMR = 1.52; 95% CI = 1.01-2.19). Exposure to ionizing radiation while at Chernobyl has not caused a detectable increase in the incidence of cancer among cleanup workers from Estonia. At least for the short follow-up period, diseases directly attributable to radiation appear to be of relatively minor importance when compared with the substantial excess of deaths due to suicide.

Thyroid nodularity and cancer among Chernobyl cleanup workers from Estonia.

Thyroid examinations, including palpation, ultrasound and, selectively, fine-needle aspiration biopsy, were conducted on nearly 2,000 Chernobyl cleanup workers from Estonia to evaluate the occurrence of thyroid cancer and nodular thyroid disease among men with protracted exposure to ionizing radiation. The examinations were conducted in four cities in Estonia during March-April 1995, 9 years after the reactor accident. The study population was selected from a predefined cohort of 4,833 cleanup workers from Estonia under surveillance for cancer incidence. These men had been sent to Chernobyl between 1986 and 1991 to entomb the damaged reactor, remove radioactive debris and perform related cleanup activities. A total of 2,997 men were invited for thyroid screening and 1,984 (66%) were examined. Estimates of radiation dose from external sources were obtained from military or other institutional records, and details about service dates and types of work performed while at Chernobyl were obtained from a self-administered questionnaire. Blood samples were collected for assay of chromosomal translocations in circulating lymphocytes and loss of expression of the glycophorin A (GPA) gene in erythrocytes. The primary outcome measure was the presence or absence of thyroid nodules as determined by the ultrasound examination. Of the screened workers, 1,247 (63%) were sent to Chernobyl in 1986, including 603 (30%) sent in April or May, soon after the accident. Workers served at Chernobyl for an average of 3 months. The average age was 32 years at the time of arrival at Chernobyl and 40 years at the time of thyroid examination. The mean documented radiation dose from external sources was 10.8 cGy. Biological indicators of exposure showed low correlations with documented dose, but did not indicate that the mean dose for the population was higher than the average documented dose. Ultrasound examinations revealed thyroid nodules in 201 individuals (10.2%). The prevalence of nodules increased with age at examination, but no significant associations were observed with recorded dose, date of first duty at Chernobyl, duration of service at Chernobyl, building the sarcophagus or working on the roof of neighboring buildings or close to the damaged reactor. Nodularity showed a nonsignificant (p(1) = 0.10) positive association with the proportion of lymphocytes with chromosome translocations, but associations with the frequency of variant erythrocytes in the GPA assay were weak and unstable (p(1) > or = 0.46). The majority of fine-needle biopsies taken on 77 study participants indicated benign nodular disease. However, two cases of papillary carcinoma and three benign follicular neoplasms were identified and referred for treatment. Both men with thyroid cancer had been sent to Chernobyl in May of 1986, when the potential for exposure to radioactive iodines was greatest. Chernobyl cleanup workers from Estonia did not experience a markedly increased risk of nodular thyroid disease associated with exposure to external radiation. Possible reasons for the apparent absence of effect include low radiation doses, the protracted nature of the exposure, errors in dose measurement, low sensitivity of the adult thyroid gland or the insufficient passage of time for a radiation effect to be expressed.

Thyroid nodularity after diagnostic administration of iodine-131.

In contrast to external X and gamma radiation, radiation from internally deposited 131I has not been clearly shown to cause thyroid tumors or nodules. Given the wide use of 131I in medicine and concern about health risks associated with the release of radioiodines from nuclear reactors, more information is needed. The purpose of this study was to evaluate the risk of thyroid nodularity among women previously exposed to radioiodine (131I) for diagnostic reasons. A clinical examination survey, including thyroid palpation, was conducted for a sample of women drawn from a cohort of patients exposed to 131I and a comparison group of women attending a mammography screening clinic. The study was conducted during 1991-1993 at Radiumhemmet, Karolinska Hospital, Stockholm, Sweden. A total of 1,005 women referred for a thyroid scintigraph or tracer test during the period 1952-1977 were included in the study. For comparison, 248 nonexposed women attending a mammography screening clinic were also enrolled. The primary outcome measure was the presence or absence of palpable thyroid nodules at the time of the clinical examination. Odds ratios were used as estimates of relative risk (RR). The mean dose to the thyroid from 131I was 0.54 Gy, and the average age at 131I administration was 26 years. The prevalence of thyroid nodularity was 10.6% among women who had been exposed to 131I and 11.7% among the nonexposed women [RR = 0.9; 95% confidence interval (CI) 0.6-1.4]. When analysis was restricted to women exposed to 131I, prevalence was associated positively with thyroid dose (excess RR = 0.9 per Gy; 95% CI 0.2-1.9). However, the excess RR was similar for women exposed before age 20 years and those exposed after age 20, which is contrary to findings for populations exposed to external radiation. While results demonstrated a positive association between diagnostic administration of 131I and the subsequent occurrence of thyroid nodules, it is unclear whether the association is causal, as the possibility of confounding by indication for 131I administration cannot be ruled out. No tumors that were subsequently diagnosed as cancer were found during the thyroid examinations, which supports the view that exposure to 131I administered for diagnostic reasons during adulthood rarely causes thyroid cancer.