Use of mammography, Pap test and prostate examination by body mass index during the developmental period of cancer screening in Estonia.

OBJECTIVES: Analysis of the use of mammography, Pap test and prostate examination (palpation and/or prostate-specific antigen test) by body mass index (BMI) in Estonia. STUDY DESIGN: Cross-sectional. METHODS: In total, 7286 individuals aged 16-64 years, randomly selected from the National Population Register, filled out questionnaires in postal surveys in 2000, 2004 and 2008. The target age group was 45-64 years for mammography, 25-64 years for Pap test and 50-64 years for prostate examination. The probability of using these preventive medical services within the past 2 years by BMI was analysed using logistic regression models. Potential confounding variables included socio-economic factors, health behaviour, number of outpatient visits, current self-rated health, study year and age. RESULTS: Compared with women of normal weight, the probability of mammography use was higher for overweight women [adjusted odds ratio (OR) 1.32, 95% confidence interval (CI) 1.01-1.73], and the probability of a Pap test was significantly lower for severely obese women (adjusted OR 0.51, 95% CI 0.35-0.76). Prostate examination was independent of BMI. In 2008, mammography was predominantly performed within the screening framework for all BMI groups (highest rate in the mild obesity group, 76.2%), while Pap tests were predominantly performed following referral by a doctor (especially in the severe obesity group, 66.7%). The attendance rate for prostate examination was higher for men who rated their current health status as rather poor/poor. CONCLUSIONS: In a country where population-based breast cancer screening works fairly well, cervical cancer screening is in its developmental stage and there is no screening for prostate cancer, the deciding role in referring people for preventive examinations for cervical and prostate cancer is still held by doctors. As such, they should pay particular attention to obese women, as this group has a worse prognosis for cervical cancer, and perform more prostate examinations for preventive purposes.

Risk factors for pulmonary tuberculosis in Estonia.

OBJECTIVE: To determine the risk factors for pulmonary tuberculosis incidence in Estonia. DESIGN: In a case-control study, the cases were 248 adult tuberculosis patients treated in a hospital in Tallinn between January 1999 and June 2000, and the controls were 248 persons sampled from the Population Registry and matched to cases by sex, year of birth and county of residence. A questionnaire was administered to collect information on potential risk factors. Logistic regression was used to calculate odds ratios and 95% confidence intervals. RESULTS: The main risk factors for tuberculosis were marital status other than married, educational level less than higher, low income, having been in prison, not having own place of residence, current unemployment, current smoking, alcohol consumption, shortage of food, and contact with tuberculosis patients. Place of birth was not a risk factor. Risk of tuberculosis decreased for overweight persons whose individual economic situation had improved during the last year. CONCLUSIONS: The pattern of risk factors for pulmonary tuberculosis in Estonia was somewhat different from that in Western European countries; a large percentage of the patients were men, but were not elderly, and immigration and drug abuse did not increase the risk. Major risk factors were related to poverty and low socio-economic status.

Studies of cancer risk among Chernobyl liquidators: materials and methods.

The current paper presents the methods and design of two case-control studies among Chernobyl liquidators-one of leukaemia and non-Hodgkin lymphoma, the other of thyroid cancer risk-carried out in Belarus, Estonia, Latvia, Lithuania and Russia. The specific objective of these studies is to estimate the radiation induced risk of these diseases among liquidators of the Chernobyl accident, and, in particular, to study the effect of exposure protraction and radiation type on the risk of radiation induced cancer in the low-to-medium- (0-500 mSv) radiation dose range. The study population consists of the approximately 10000 Baltic, 40000 Belarus and 51 000 Russian liquidators who worked in the 30 km zone in 1986-1987, and who were registered in the Chernobyl registry of these countries. The studies included cases diagnosed in 1993-1998 for all countries but Belarus, where the study period was extended until 2000. Four controls were selected in each country from the national cohort for each case, matched on age, gender and region of residence. Information on study subjects was obtained through face-to-face interview using a standardised questionnaire with questions on demographic factors, time, place and conditions of work as a liquidator and potential risk and confounding factors for the tumours of interest. Overall, 136 cases and 595 controls after receiving their consent were included in the studies. A method of analytical dose reconstruction has been developed, validated and applied to the estimation of doses and related uncertainties for all the subjects in the study. Dose-response analyses are underway and results are likely to have important implications to assess the adequacy of existing protection standards, which are based on risk estimates derived from analyses of the mortality of atomic bomb survivors and other high dose studies.

Persistence of translocations after accidental exposure to ionizing radiation.

PURPOSE: To assess the validity of translocations for retrospective biodosimetry using FISH chromosome painting of peripheral lymphocytes in repeated samples of people accidentally exposed to radiation. MATERIALS AND METHODS: Blood samples from five people exposed to mainly whole-body irradiation of gamma-rays from a radiation accident in Estonia in 1994 were taken at 2-4 month intervals. A total of eight samplings were carried out, including one directly after the accident. Fluorescence in situ hybridization with probes for chromosomes 1, 2 and 4 was performed on metaphase preparations from 48 h whole blood cultures; 1500 cells were scored from each individual per time point. RESULTS: Translocations remained relatively stable during 2 years after exposure in all subjects. A noticeable decrease in complete translocation yields and a significant decrease in incomplete translocations were observed in one person. In addition to whole-body exposure, he had also been exposed to partial-body irradiation. Due to the overall persistence of translocations, dose estimates were very similar throughout the 2 year period. A rapid decline in dicentric frequencies was noted during the first year after exposure. CONCLUSIONS: The results suggest that during 2 years the yield of translocations in peripheral lymphocytes remained at a constant level after whole-body exposure. This finding supports the use of translocations for retrospective dosimetry, at least within this relatively short period of follow-up. In the case of partial-body irradiation, however, the elimination of co-existing unstable aberrations reduced the translocation yield over time. Follow-up will be continued in order to determine the stability of translocations over longer times.

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.

Chromosomal instability in in vivo radiation exposed subjects.

PURPOSE: To investigate whether delayed chromosomal instability arises in human peripheral T lymphocytes exposed in vivo to gamma-irradiation. MATERIALS AND METHODS: Long-term cultures were established from lymphocytes obtained from subjects involved in the radiological accident in Estonia in 1994. Two individuals exposed to a high dose, one individual with low exposure and one apparently unexposed person were studied. Two Estonian controls not involved with the accident were also analysed. Cells were grown for 6-42 days and chromosomal aberrations were assessed from G-banded metaphases. In addition, FISH chromosome painting analysis was performed on short-term cultures established from whole blood. RESULTS: No obvious sign of chromosomal instability was observed in the in vivo follow-up of the frequencies of chromosomal aberrations in lymphocytes of radiation accident victims performed by the FISH technique (48 h cultures established at different time intervals after the exposure). However, when the lymphocytes were cultured long term in vitro, chromosomal instability was observed. There was no dose-response, and the appearance of chromosomally unstable cells in long-term cultures was also observed in a subject exposed to a dose of less than 0.1 Gy. Moreover, in contrast with previous findings, chromosomal instability was also observed in cells from non-exposed control individuals. The chromosomal changes observed in the controls were less complex than the aberrations in the cultures derived from individuals exposed to high doses. CONCLUSIONS: Chromosomal instability was observed in long-term cultures of donors with in vivo exposure to gamma-radiation. No dose-response was apparent. However, in contrast with previous findings, signs of chromosomal instability were observed also in long-term cultures from non-exposed controls. Further studies are needed to assess possible inter-individual differences in the induction of chromosomal instability.

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.

Biodosimetry of Chernobyl cleanup workers from Estonia and Latvia using the glycophorin A in vivo somatic cell mutation assay.

The reactor accident at Chernobyl in 1986 necessitated a massive environmental cleanup that involved over 600,000 workers from all 15 Republics of the former Soviet Union. To determine whether the whole-body radiation received by workers in the course of these decontamination activities resulted in a detectable biological response, over 1,500 blood samples were obtained from cleanup workers sent from two Baltic countries, Estonia and Latvia. Here we report the results of studies of biodosimetry using the glycophorin A (GPA) locus in vivo somatic cell mutation assay applied to 734 blood samples from these workers, to 51 control samples from unexposed Baltic populations and to 94 samples from historical U.S. controls. The data reveal inconsistent evidence that the protracted radiation exposures received by these workers resulted in a significant dose-associated increase in GPA locus mutations compared with the controls. Taken together, these data suggest that the average radiation exposure to these workers does not greatly exceed 10 cGy, the minimum levels at which radiation effects might be detectable by the assay. Although the protracted nature of the exposure may have reduced the efficiency of induction of GPA locus mutations, it is likely that the estimated physical doses for these cleanup worker populations (median reported dose 9.5 cGy) were too low to result in radiation damage to erythroid stem cells that can be detected reliably by this method.

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.

Biodosimetry after accidental radiation exposure by conventional chromosome analysis and FISH.

A 137Cs source was stolen from a radioactive waste depository in Estonia on 21 October 1994 and kept in a private house for 4 weeks. This resulted in the death of one person, acute radiation injuries to four people and exposure of several other people to lower doses of radiation. Analysis of chromosomal aberrations in peripheral blood lymphocytes was used in the assessment of radiation exposure of 18 people involved in the accident. Dose estimation assessment based on the frequencies of dicentric chromosomes was performed both by the standard method and by considering possible dose protraction and non-uniform exposure. Considerable differences in dose estimates were obtained depending on the approach used, ranging from about 1 Gy to almost 3 Gy in the patients most heavily exposed. In view of the deterministic health effects observed in some of the subjects, it was concluded that the dose estimates involving information on dose protraction were more realistic than those obtained by comparison with the standard high dose-rate calibration curve. Chromosome painting analyses using fluorescence in situ hybridization, with a probe cocktail for chromosomes 1, 2 and 4 and centromere detection, were performed in parallel. Good agreement on dicentric chromosome frequencies was observed between the conventional and painting analyses. The frequencies of complete translocations were comparable with the frequencies of dicentric chromosomes. In addition to the complete translocations, a pronounced increase in the frequency of incomplete translocations was observed. Dose estimates performed on the basis of FISH translocation frequencies were consistent with the dicentric analysis.

Retrospective dose estimates in Estonian Chernobyl clean-up workers by means of FISH.

The present study deals with retrospective estimation of radiation doses, among Estonian Chernobyl clean-up workers, by means of scoring stable translocations using the FISH technique. All persons investigated in this study were sent to the area in 1986 and the majority of them were selected to be among those with the presumably highest exposure doses. In spite of the selection the estimated average dose is between 0.2-0.3 Gy, thus not clearly above the officially permitted dose level of 0.25 Gy. Due to unforseen conditions during transport of the blood samples, both the number of persons available for analysis and the number of metaphases available for scoring were substantially reduced. However, unless this selection is linked with the potential aberration frequency of the cells involved, no bias is expected.

[Diagnostic effectiveness of mammography in various age groups]. / Diagnosticheskaia éffektivnost' mammografii v raznykh vozrastnykh gruppakh.

The diagnostic efficacy of 935 mammographies from the mammology service for self-referred symptomatic women was assessed for the period of 1975-1988. Breast cancer was detected in 200 women. The paper is concerned with the distribution of true- or false-positive and true- or false-negative mammographic diagnoses in the age groups of women under 40, 40 to 49 and over 49. The sensitivity of mammography in these age groups was 87.5, 72.4 and 89%, the specificity was 83.5, 76.4 and 83%, and the positive predictive values were 42, 38.2 and 69.5%, respectively.

[The organization of breast self-examination among women in the Estonian SSR]. / Organizatsiia samoobsledovaniia molochnykh zhelez u zhenshchin v Estonskoi SSR.

Patients with breast cancer and healthy females (150 in each group) aged 40-64 years were examined to assess the extent of breast self-examination development in Estonia. Breast cancer was detected by self-examination in 82.0% of cases. The occurrence of stage I tumors detected by the physician was comparable to that in the self-examination group. Breast self-examination was practised by 69.3% of healthy females and 42.7% of patients. Most of them had read about the method in the literature. Early detection of breast cancer can be assured provided breast self-examination is performed regularly.

Survival of female breast cancer patients in Finland and in Estonia: stage at diagnosis important determinant of the difference between countries.

The survival experiences of female breast cancer patients diagnosed in 1968-81 in Finland and in Estonia were compared. The series consisted of 18,729 patients in Finland and 4100 in Estonia. The overall estimated 5-year relative survival rate was 67.3% in Finland and 55.9% in Estonia. The stage-adjusted 5-year relative survival rate in Estonia was 63.4% (the Finnish rates used as a standard). Older patients in Finland had much higher survival rates than older patients in Estonia. There was a clear difference in the stage distribution in Estonia between older and younger age groups, with non-localized cases occurring in older age groups. No such difference was noticed in Finland. It seems that the diagnostic lag for older women is longer in Estonia than in Finland. In Estonia older patients seek medical assistance later, or symptoms and signs of younger patients are more effectively studied.