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.

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.

Lung cancer risk and radiation dose among women treated for breast cancer.

BACKGROUND: Evidence shows ionizing radiation can cause lung cancer, but few studies have quantified risk in relation to radiation dose. PURPOSE: This study evaluated the long-term risk of lung cancer among women treated with radiation for breast cancer. METHODS: In this case-referent study, the Connecticut Tumor Registry was used to identify women diagnosed with histologically confirmed invasive breast cancer between 1935 and 1971 who survived for at least 10 years (8976) and to ascertain lung cancers occurring in this group between 1945 and 1981. Seventy-six cases of lung cancer were identified; however, 15 cases did not meet the criteria for inclusion. For the 61 remaining lung cancer case patients and 120 reference subjects (selected from the same registry and matched according to race, age at breast cancer diagnosis, year of breast cancer diagnosis, and survival without a second primary tumor), hospital charts were reviewed to collect medical history and radiotherapy information. A medical physicist estimated radiation dose to different segments of the lungs on the basis of radiotherapy reports and experimental simulations of treatments. RESULTS: For these 10-year survivors of breast cancer, the overall relative risk (RR) of lung cancer associated with initial radiotherapy for breast cancer was 1.8 (95% confidence interval [CI] = 0.8-3.8), and the RR increased with time following treatment. The RR for periods of 15 years or more after radiotherapy was 2.8 (95% CI = 1.0-8.2). Mean dose was 15.2 Gy to the ipsilateral lung, 4.6 Gy to the contralateral lung, and 9.8 Gy for both lungs combined. The excess RR was 0.08 per Gy, based on average dose to both lungs, and 0.20 per Gy to the affected (cancerous) lung. CONCLUSIONS: Breast cancer radiotherapy regimens in use before the 1970s were associated with an elevated lung cancer risk many years following treatment. The estimated risk coefficients are lower than those reported for atomic bomb survivors. The lower than expected risk might be attributable to high-dose cell killing or the fractionated nature of the exposure. IMPLICATIONS: Approximately nine cases of radiotherapy-induced lung cancer per year would be expected to occur among 10,000 women who received an average lung dose of 10 Gy and survived for at least 10 years. Current radiotherapy for breast cancer results in less extensive exposure of the lungs in comparison to treatments of years past, and the risk of secondary lung cancer need not play a major role in clinical decisions regarding treatment for breast cancer. Nonetheless, efforts to reduce unnecessary exposure of the lungs and heart should continue to further reduce possible adverse radiation effects.

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.

Serum estrogen and androgen levels following treatment for cervical cancer.

Endogenous sex hormones seem to influence the risk of several common and debilitating diseases. With a view toward better understanding the effects of surgical removal of the ovaries and high-dose pelvic radiotherapy on plasma sex hormone levels, we measured estrogen and androgen concentrations cross-sectionally among 147 women who had been treated for cervical cancer 0.3-18.5 years previously. Pelvic radiotherapy (mean dose to ovaries, 50 Gy) and bilateral ovariectomy were associated with similarly reduced hormone concentrations relative to levels among nonirradiated women with intact ovaries, most of whom had had early-stage disease and were treated by hysterectomy. There was little evidence that radiotherapy in addition to ovariectomy further lowered concentrations below levels associated with ovariectomy alone, such as might be expected if radiation was suppressing adrenal endocrine function. Among women age 50 years or older at the time of blood drawing, the removal or irradiation of the ovaries was associated with approximately 45% lower concentrations of estradiol (mean ratio [MR], 0.55; 95% confidence interval [CI], 0.32-0.95) and testosterone (MR, 0.57; 95% CI, 0.32-0.99), and 25-30% lower concentrations of estrone (MR, 0.69; 95% CI, 0.44-1.09) and androstenedione (MR, 0.76; 95% CI, 0.47-1.23), relative to the hysterectomy-only group. Among women younger than 50, ovariectomy and radiotherapy, alone or in combination, were associated with 83% lower estradiol concentrations (MR, 0.17; 95% CI, 0.09-0.31), 46% lower estrone concentrations (MR, 0.54; 95% CI, 0.37-0.81), 23% lower androstenedione concentrations (MR, 0.77; 95% CI, 0.57-1.04), and 14% lower testosterone levels (MR, 0.86; 95% CI, 0.64-1.15).(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Ionizing radiation: future etiologic research and preventive strategies.

Estimates of cancer risks following exposure to ionizing radiation traditionally have been based on the experience of populations exposed to substantial (and known) doses delivered over short periods of time. Examples include survivors of the atomic bombings at Hiroshima and Nagasaki, and persons treated with radiation for benign or malignant disease. Continued follow-up of these populations is important to determine the long-term effects of exposure in childhood, to characterize temporal patterns of excess risk for different types of cancer, and to understand better the interactions between radiation and other host and environmental factors. Most population exposure to radiation occurs at very low dose rates. For low linear energy transfer (LET) radiations, it often has been assumed that cancer risks per unit dose are lower following protracted exposure than following acute exposure. Studies of nuclear workers chronically exposed over a working lifetime provide data that can be used to test this hypothesis, and preliminary indications are that the risks per unit dose for most cancers other than leukemia are similar to those for acute exposure. However, these results are subject to considerable uncertainty, and further information on this question is needed. Residential radon is the major source of population exposure to high-LET radiation. Current estimates of the risk of lung cancer due to residential exposure to radon and radon daughters are based on the experience of miners exposed to much higher concentrations. Data indicate that lung cancer risk among miners is inversely associated with exposure rate, and also is influenced by the presence of other lung carcinogens such as arsenic in the mine environment. Further study of populations of radon-exposed miners would be informative, particularly those exposed at below-average levels. More direct evidence on the effects of residential exposure to radon also is desirable but might be difficult to come by, as risks associated with radon levels found in most homes might be too low to be quantified accurately in epidemiological studies.

A novel approach to data collection in a case-control study of cancer and occupational exposures.

BACKGROUND: In community and hospital-based case-control studies, the occupational data collected in interviews are usually limited to responses to general questions asked of all study subjects. A procedure is described in which more detailed information can be collected in an efficient, standardized and systematic way. METHODS: A generic work history is initially collected from all subjects using a computer-assisted interview. The work history includes job title, type of business, job activities, materials and chemicals, and tools and equipment used. After responses are entered into the computer by the interviewer, the computer searches a synonym file to identify possible job-specific modules relevant to the reported job. The modules are detailed questionnaires that address specific jobs administered after obtaining the generic work history. The modules are used to ask questions about the work environment; sources of exposure; factors affecting the movement of the agent from the source to the subject, such as local exhaust ventilation; and individual and job characteristics. After the interview is completed, the work history and responses to the modules are sent electronically to an industrial hygienist who reviews the information using a custom-designed software package. Where ambiguities or contradictions occur in information reported by the respondent, or for jobs for which no module had been developed, the industrial hygienist generates up to 10 additional questions per job. These questions are sent back to the interviewer for administration of a short, second interview. CONCLUSIONS: These procedures, which are being successfully implemented in an on-going case-control study of brain tumours, should improve disease risk estimates over those derived from more traditional approaches to exposure assessment.

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.

Cancer mortality following radium treatment for uterine bleeding.

Cancer mortality in relation to radiation dose was evaluated among 4153 women treated with intrauterine radium (226Ra) capsules for benign gynecologic bleeding disorders between 1925 and 1965. Average follow up was 26.5 years (maximum = 59.9 years). Overall, 2763 deaths were observed versus 2687 expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.03]. Deaths due to cancer, however, were increased (SMR = 1.30), especially cancers of organs close to the radiation source. For organs receiving greater than 5 Gy, excess mortality of 100 to 110% was noted for cancers of the uterus and bladder 10 or more years following irradiation, while a deficit was seen for cancer of the cervix, one of the few malignancies not previously shown to be caused by ionizing radiation. Part of the excess of uterine cancer, however, may have been due to the underlying gynecologic disorders being treated. Among cancers of organs receiving average or local doses of 1 to 4 Gy, excesses of 30 to 100% were found for leukemia and cancers of the colon and genital organs other than uterus; no excess was seen for rectal or bone cancer. Among organs typically receiving 0.1 to 0.3 Gy, a deficit was recorded for cancers of the liver, gall bladder, and bile ducts combined, death due to stomach cancer occurred at close to the expected rate, a 30% excess was noted for kidney cancer (based on eight deaths), and there was a 60% excess of pancreatic cancer among 10-year survivors, but little evidence of dose-response. Estimates of the excess relative risk per Gray were 0.006 for uterus, 0.4 for other genital organs, 0.5 for colon, 0.2 for bladder, and 1.9 for leukemia. Contrary to findings for other populations treated by pelvic irradiation, a deficit of breast cancer was not observed (SMR = 1.0). Dose to the ovaries (median, 2.3 Gy) may have been insufficient to protect against breast cancer. For organs receiving greater than 1 Gy, cancer mortality remained elevated for more than 30 years, supporting the notion that radiation damage persists for many years after exposure.

Leukemia following radiotherapy for uterine bleeding.

Mortality due to leukemia among 4483 women treated with radiation to control uterine bleeding between 1925 and 1965 was twice as high as expected based on U.S. population rates (standardized mortality ratio (SMR) = 2.0; 95% confidence interval (CI): 1.4 to 2.8). Women were followed for an average of 26.4 years. Relative risk was highest 2 to 5 years after treatment (SMR = 8.1) and among women over 55 years at irradiation (SMR = 5.8). The usual method of treatment was intrauterine radium. Average radiation dose to active bone marrow was estimated on the basis of original radiotherapy records (median, 53 cGy). A linear dose-response model provided an adequate fit to the data. The average excess relative risk was 1.9% per cGy (95% CI: 0.8 to 3.2), and the average absolute risk was 2.6 excess leukemia deaths per million women per year per cGy (95% CI: 0.9 to 4.8). Chronic myeloid leukemia predominated during the first 15 years following exposure, whereas acute leukemias and chronic lymphatic leukemia were most common thereafter. The radiation doses experienced during treatment of benign gynecologic disease appear to result in greater leukemia risk per cGy average marrow dose than the considerably higher doses used to treat malignant disease, perhaps because of a decreased likelihood of killing potentially leukemic cells.

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.

Leukemia, lymphoma, and multiple myeloma after pelvic radiotherapy for benign disease.

The relationship between exposure to sparsely ionizing radiation and mortality due to cancers of hematopoietic and lymphopoietic tissues was studied among 12,955 women treated for benign gynecological disorders at any of 17 hospitals in New England or New York State and followed for an average of 25 years; 9770 women were treated by radiation (intracavitary 226Ra, external-beam X rays), while 3185 were treated by other methods, including curettage, surgery, and hormones. The average age at treatment was 46.5 years, and the mean dose to active bone marrow among irradiated women was 119 cGy. Forty deaths due to acute, myelocytic, or monocytic leukemia were observed among irradiated women. This number was 70% higher than expected based on U.S. mortality rates [standardized mortality ratio (SMR) = 1.7; 90% confidence interval (CI) 1.3-2.3]. A deficit was recorded among nonirradiated women, based on three observed deaths (SMR = 0.5; 90% CI 0.1-1.2). A well-defined gradient in the SMR with dose among exposed women was not detected. The SMR was highest within 5 years after irradiation but remained elevated even after 30 years. The temporal pattern differed by subtype of leukemia: excess mortality due to chronic myelocytic leukemia occurred almost exclusively within the first 15 years, whereas the SMR for acute leukemia, though also elevated, varied little over time. Cancers of lymphoreticular tissue occurred more often than expected based on U.S. mortality rates, but not appreciably differently for irradiated and nonirradiated women. There was little or no evidence of effects attributable to radiotherapy for chronic lymphocytic leukemia [relative risk (RR) = 1.1; 90% CI 0.5-3.0], Hodgkin's disease (RR = 0.9; 90% CI 0.3-3.2), non-Hodgkin's lymphoma (RR = 0.9; 90% CI 0.6-1.6), or multiple myeloma (RR = 0.6; 90% CI 0.3-1.4). These results corroborate previous findings indicating that acute and myelocytic leukemias are the most prominent malignancies after exposure to sparsely ionizing radiation, occurring in excess shortly after irradiation, and that lymphomas are either not caused by radiation or are induced only rarely.

Chromosome aberrations in lymphocytes from women irradiated for benign and malignant gynecological disease.

Excess leukemias have occurred after partial-body radiotherapy for cervical cancer and benign gynecological disease (BGD). However, the level of risk is nearly the same in both groups, about twofold, despite a tenfold difference in average dose to active bone marrow (8 Gy vs 0.7 Gy, respectively). High-dose cell killing has been postulated as one explanation for this apparent inconsistency. To examine whether chromosome aberration rates observed in lymphocytes many years after exposure might serve as population markers of cancer risk, blood samples were taken from 60 women treated for BGD (34 with radiation) and cytogenetic data compared with previous results from 96 women irradiated for cervical cancer. Remarkably, the rate of stable aberrations, which reflects nonlethal damage in surviving stem cells, was only slightly higher among the cancer patients. Thus the lower-dose regimens to treat benign disorders resulted in much higher aberration yields per unit dose than those for cervical cancer. Assuming that the fraction of cytogenetically aberrant stem cells that survive radiotherapy contributes to the leukemogenic process, these data are then consistent with the epidemiological observations of comparable overall leukemia risks seen in these two irradiated populations. Accordingly, for patient populations given partial-body radiotherapy, stable aberrations at a long time after exposure appear to serve as biomarkers of effective risk rather than as biomarkers of radiation dose received.

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.

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.

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).

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.