Cancer In Belarus Research Articles

Relationship of the expression of the NF1, p53, bcl-2, pRB proteins with DNA/RNA of viruses and mutations of the BRCA 1/2 and hMSH2 genes in liver cancer

Among tumors of the gastrointestinal tract, the incidence and mortality from primary liver cancer remains high. Over the past 20 years, the incidence of liver cancer in Belarus has increased by 45.7 %. The aim of the study was to establish the relationship between the expression of the NF1, p53, bcl-2 proteins and the pRB genes with DNA/RNA of viruses and mutations of the BRCA 1/2 and hMSH2 genes in liver cancer. Patients (n = 303) with morphologically established primary liver cancer were examined. A molecular biological and immunological study was performed: antibodies to cell-cycle NF1, p53, bcl-2, pRB proteins, DNA/RNA of viruses, the BRCA 1/2, hMSH2 gene. The levels of antibodies to p53, bcl-2, pRB, and NF1 in the serum of healthy individuals differed from those in blood samples and tissue extracts from patients with hepatitis C, liver cancer and in native liver tissue samples. Mutations in liver cancer were (p = 0.004): in the tumor tissue – 6.13 %, in the blood – 0.85 %. Changes in the hMSH2 gene in the tissue were set at 15.48 %. DNA/RNA was isolated in the tumor tissue: HSV 1/2 – 56.1 %, HHV6 – 24.4, CMV – 17.1, HCV – 17.1, HBV – 4.9, HPV – 4.1, VEB – 2.4 %. Including mixed persistence – 26.8 %. In hepatitis (C, B) and liver cancer with CMV carriers, the expression of bcl-2, NF1 and pRb1 (p = 0.001) increases. The Epstein–Barr virus leads to the activity of the p53 protein in liver cancer (p = 0.003). The p53, bcl-2, pRB, and NF1 proteins in the liver tissue do not depend on the age and sex of patients. The degree of their influence on the function of genes with regard to DNA/RNA of viruses and mutations present in the genome (BRCA 1/2, hMSH2) suggests the degree of oncogenicity of viruses. The concentrations of p53, bcl-2, pRB, and NF1 in the blood, exceeding the predicted ones, for 50.8 year old persons, indicate the risk of development/presence of a tumor process in the liver.

Low Survival in Poor Prognosis Metastatic Germ Cell Cancer in Belarus.

PURPOSESince the development of the International Germ Cell Cancer Collaborative Group (IGCCCG) risk classification in a 1997 study, high-income countries have reported a significant increase in survival for poor prognosis patients. There are scant data on IGCCCG risk-stratified survival from low- and middle-income countries. We assessed the progression-free survival (PFS) and overall survival (OS) rates in a contemporary cohort of Belarusian patients with advanced germ cell cancer (GCC) stratified by the IGCCCG prognostic classification and analyzed prognostic factors for survival.MATERIALS AND METHODSThe consecutive cohort of patients with clinical stage IIb-III testicular GCC or extragonadal germ cell tumors who received treatment or consultation in our two centers between 2010 and 2015 was included. All patients underwent primary chemotherapy. The patients were divided into seminoma and nonseminomatous germ cell carcinoma (NSGCC) subgroups. The Kaplan-Meier method was used to estimate 5-year PFS and OS.RESULTSThis study included 111 patients with a median age of 32 years, 95% of whom were diagnosed with testicular cancer. Seminoma and NSGCC were identified in 32 (29%) and 79 (71%) patients, respectively. The median follow-up was 6.1 years. The 5-year PFS and OS rates for the entire cohort were 70% and 77%, respectively. In patients with good prognosis seminoma and good, intermediate, and poor prognosis NSGCC, the estimated PFS rates were 76%, 88%, 74%, and 39% and those for OS were 83%, 97%, 83%, and 38%, respectively.CONCLUSIONIn our cohort of Belarusian patients with advanced germ cell tumors, we failed to demonstrate an improvement in PFS and OS compared with the 1997 IGCCCG study. Moreover, survival in poor prognosis group is inferior to that in IGCCCG and all contemporary series from high-income countries.

Iodine in Soils and Potatoes Produced in Private Farms of Bryansk and Gomel Regions Located in the Impact Zone of the Chernobyl Accident

Among residents of the Bryansk and Gomel regions of Russia and Belarus, who were exposed to the so-called “iodine attack” as a result of the 1986 Chernobyl Nuclear Power Plant accident, there was a sharp increase in thyroid disease. Therefore, the natural iodine deficiency in soils was an important additional risk factor that could cause adverse reactions primarily among children, for whom the incidence of thyroid cancer in Belarus increased by 76 times. Potatoes belong to one of the main ration-forming foods for local population. In this regard, in 2007–2017, 97 settlements were surveyed in the affected areas, in which samples of local arable soils and potatoes were taken from 138 private subsidence farms (PFs).The iodine content in the studied soils of the private farms of the Bryansk region ranged from 0.11 to 3.5 mg/kg (air-dry weight). The content of iodine in potatoes grown on these soils varied within a considerably wider interval: from 0.002 to 0.119 mg/kg (wet weight), averaging 0.033 mg/kg, which indicates a generally low iodine transfer to this particular product. The data obtained deserve attention when organizing monitoring and carrying out measures for the prevention of iodine deficiency.

82 - Treatment burden in patients with testicular cancer in Belarus

82 - Treatment burden in patients with testicular cancer in Belarus

PO-067 Thyroid cancer incidence in belarusian residents exposed to chernobyl fallout

IntroductionThe accident at the Chernobyl nuclear power plant was the largest radiation-ecological catastrophe, which was accompanied by a massive release of the radioactive isotope of iodine. The aim of this work was to investigate the incidence of thyroid cancer in Belarus and assess the risk of developing this disease in various groups of affected cohorts.Material and methodsThe data from the State Register of persons affected by the Chernobyl accident (from 1987 to 2015) and the data of the Belarusian Cancer Registry (from 1978 to 2015) were used in the study. The analysis was conducted using crude rates (CR), age-specific rates (AsR) and age-standardised rates (ASR) and standardised incidence ratio (SIR). Affected population was divided into four groups: liquidators (99 498 persons), evacuees (13 096 persons), residents of contaminated areas (139 811 persons) and their offspring (30 475 persons), which were analysed by sex, age at time of the disaster, year of being in contaminated area, duration of staying in contaminated area, density of radiation contamination and individualised doze in thyroid gland.Results and discussionsIt was shown the intensive increase in the incidence rates of thyroid cancer in the Belorussian population after the Chernobyl accident, which finished after 2001 (CR1986=1.5±0.24, CR2001=10.3±0.63, CR2015=12.5±0,71). Thyroid cancer growth was most significant in most contaminated Gomel, Mogilev and Brest areas. It was shown that the maximum increase in incidence was observed in persons aged 0–4 years at the time of the accident. In the affected population, significantly high risk of thyroid cancer was noted in all groups. The risk was highest in the evacuees in 1995–1999 (SIR=13.0 (9.21–17.70)) and was significantly higher than in the liquidators (SIR=4.4 (3.63–5.25)) and in the cohort of living in contaminated areas (SIR=2,4 (1.88–2.98)). The risk was higher in men than in women, for those who were children at the time of the accident and who were in the most contaminated areas. The dose-response relationship was shown for the evacuees (rSpearman=0.9, p=0.037) and for persons living in contaminated areas (rSpearman=1.0, p<0.001). For the group of liquidators, the dose-effect relationship was not noted (rSpearman=−0.48, p=0.329).ConclusionIn our work we have shown that Chernobyl disaster increased thyroid cancer incidence in both whole population and most affected groups. Especially in people who were children at the time of disaster.

Major Factors Affecting Incidence of Childhood Thyroid Cancer in Belarus after the Chernobyl Accident: Do Nitrates in Drinking Water Play a Role?

One of the major health consequences of the Chernobyl Nuclear Power Plant accident in 1986 was a dramatic increase in incidence of thyroid cancer among those who were aged less than 18 years at the time of the accident. This increase has been directly linked in several analytic epidemiological studies to iodine-131 (131I) thyroid doses received from the accident. However, there remains limited understanding of factors that modify the 131I-related risk. Focusing on post-Chernobyl pediatric thyroid cancer in Belarus, we reviewed evidence of the effects of radiation, thyroid screening, and iodine deficiency on regional differences in incidence rates of thyroid cancer. We also reviewed current evidence on content of nitrate in groundwater and thyroid cancer risk drawing attention to high levels of nitrates in open well water in several contaminated regions of Belarus, i.e. Gomel and Brest, related to the usage of nitrogen fertilizers. In this hypothesis generating study, based on ecological data and biological plausibility, we suggest that nitrate pollution may modify the radiation-related risk of thyroid cancer contributing to regional differences in rates of pediatric thyroid cancer in Belarus. Analytic epidemiological studies designed to evaluate joint effect of nitrate content in groundwater and radiation present a promising avenue of research and may provide useful insights into etiology of thyroid cancer.

BRCA1 founder mutations and ovarian cancer in Belarus

In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases. BRCA1 mutations also predispose to ovarian cancer. The aim of this study was to estimate the frequency of the three BRCA1 founder mutations in Belarus. The study group consisted of 134 consecutive, newly diagnosed cases of ovarian cancer after surgical treatment, unselected for age or family history. The control group constituted 853 blood samples from newborn children (417 girls and 436 boys). All patients were inhabitants of the western region of Belarus. DNA was extracted from peripheral blood lymphocytes for cases and from cord blood from afterbirth. Two BRCA1 mutations (4153delA and 5382insC) were studied using ASA-PCR and one mutation (C61G) was detected with RFLP-PCR. A mutation was identified in 9 of 853 newborn controls (1.1%). The 5382insC mutation was the most common (78%). A BRCA1 mutation was detected in 18 of the 134 (13.4%) unselected ovarian cancer cases. The median age of diagnosis of the 18 hereditary ovarian cancers was 54±10 years. (range 41–79 years). The frequency of a BRCA1 mutation in underlying population and hereditary proportion of ovarian cancer in Belarus is among the highest of any countries studied to date.

Polymorphism of DNA repair genes OGG1, XRCC1, XPD and ERCC6 in bladder cancer in Belarus

Context: The study of DNA base and nucleotide excision repair gene polymorphisms in bladder cancer seems to have a predictive value because of the evident relationship between the DNA damage response induced by environmental mutagens and cancer predisposition.Objective: The objective was to determine OGG1 Ser326Cys, XRCC1 Arg399Gln, XPD Asp312Asn, and ERCC6 Met1097Val polymorphisms in bladder cancer patients as compared to controls.Methods: Both groups were predominantly represented by Belarusians and Eastern Slavs. DNA samples from 336 patients and 370 controls were genotyped using a PCR-RFLP method.Results: The genotype distributions were in agreement with the Hardy–Weinberg equilibrium. The minor allele frequencies in the control population were in the range of those in Caucasians in contrast to Asians. The OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes were inversely associated with cancer risk (OR [95% CI] = 0.69 [0.50–0.95] and 1.35 [1.0–1.82], respectively). The contrasting effects of these genotypes were potentiated due to their interactions with smoking habit or age.Conclusions: Among four DNA repair gene polymorphisms, the OGG1 326 Ser/Cys and XPD 312 Asp/Asn heterozygous genotypes might be recognized as potential genetic markers modifying susceptibility to bladder cancer in Belarus.

BRCA1 founder mutations compared to ovarian cancer in Belarus

In Belarus and other Slavic countries, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases, but the data on contribution of these mutations to ovarian cancers are limited. To estimate the proportion of ovarian cancers in Belarus, which are dependent on BRCA1 Slavic founder mutations, we sought the presence of three most frequent mutations (BRCA1: 5382insC, C61G and, 4153delA) in 158 consecutive unselected cases of ovarian cancer. One of the three founder mutations was present in 25 of 158 unselected cases of ovarian cancer (15.8 %). We recommend that all cases of ovarian cancer in Belarus be offered genetic testing for these founder mutations. Furthermore, genetic testing of the Belarusian population will provide the opportunity to prevent a significant proportion of ovarian cancer.

Treatment efficacy of uterine cervix cancer in Belarus

Treatment efficacy of uterine cervix cancer in Belarus

Clinical experiences with radiation induced thyroid cancer after chernobyl.

The risk of developing thyroid cancer increases considerably after exposure to external or internal radiation, especially in children below the age of 10. After the Chernobyl reactor accident, the yearly incidence of childhood thyroid cancer in Belarus increased to approximately 40 per 1.000.000 in girls and to roughly 20 per 1.000.000 in boys compared to approximately 0.5 cases per 1.000.000 prior to the accident. Typically, young children with thyroid cancer after radiation exposure present in ≈95% of the cases as papillary cancers, in ≈50% as invasive tumors growing outside the thyroid capsule, in ≈65% with lymph node metastases and in ≈15% with distant metastases. A joint Belarusian-German project starting in April 1993 that combined treatment with surgery and radioiodine was organized in 237 selected children from Belarus who were exposed to the Chernobyl fallout and had advanced stages of thyroid cancer. The study group included 141 girls and 96 boys. Their median age at the time of the accident was 1.7 years; whereas the median age at the time of diagnosis was 12.4 years. With the exception of two cases with follicular histology, the majority of the patients had been diagnosed with papillary thyroid cancers. In 63%, the tumor had grown outside the thyroid capsule and invaded the tissue of the neck (pT4). Nearly all of the selected cases (96%) showed-up with lymph node metastases (pN1) and 43% of the patients with distant metastases mainly to the lungs (pM1). In 58% of the children, complete remissions of thyroid cancer could be achieved until December 31st 2010 and in 34% of the children, stable partial remissions; in the remaining 8% of the patients, partial remissions were observed. The risk of radiation-induced thyroid cancer increased considerably in children and adolescents who were affected by the Chernobyl reactor accident. In spite of the fact, that thyroid cancers in young children seem to behave more aggressively than in older patients, the results of combined treatment with thyroidectomy, radioiodine therapy and thyroid hormone replacement are excellent.

The contribution of founder mutations in BRCA1 to breast cancer in Belarus

Mutations in the BRCA1 gene increase susceptibility to both breast and ovarian cancer. In some countries, including several in Eastern Europe, founder mutations in the BRCA1 gene are responsible for a significant proportion of breast cancer cases. To estimate the hereditary proportion of breast cancer in Belarus, we sought the presence of any of three founder mutations in BRCA1 (4153delA, 5382insC and C61G) in 500 unselected cases of breast cancer. These mutations have previously been identified in breast/ovarian cancer families from Belarus and from other Slavic countries, including Poland and Russia. One of the three founder mutations in BRCA1 was present in 38 of 500 unselected cases of breast cancer (7.6%). A mutation was found in 12.6% of women diagnosed before age 50 and 5.6% of women diagnosed after age 50. A mutation was identified in 2 of 251 newborn controls (0.8%). The hereditary proportion of breast cancers in Belarus is among the highest of any countries studied to date.

3516 Trends in incidence rates of tobacco-related cancer in Belarus, 1970–2005

Cancer incidence rates in Lebanon have been lacking for over three decades. National data based on a total of 4388 cases diagnosed during the year 1998 were reviewed and analyzed.Crude and age-standardized rates (ASRs) per 100,000 population were calculated and results were contrasted with estimates from developed and selected developing countries in the region.Among males, bladder (18.5%), prostate (14.2%), and lung cancer (14.1%) were the most frequently reported malignancies. Among females, breast cancer alone accounted for over a third of all cancers, followed by colon cancer (5.8%), and cancer of the corpus uteri (4.8%). Sex-differentials in incidence rates were highest for tobacco-related cancers (lung, larynx, and bladder). Compared with current estimates worldwide, ASRs for bladder cancer in Lebanon showed strikingly high rates. Whereas ASRs for breast and prostate cancer remained lower than those observed in developed countries, they were greater than those estimated from neighboring countries with a similar epidemiological transition as Lebanon.Findings of the comparative assessments most likely reflect differentials in prevalence of risk factors and lifestyle variables (e.g., lung and breast cancers) and can be partly explained by improvement in cancer detection rate in recent years (for prostate cancer). The implications of the results in light of primary prevention activities, screening practices, and research initiatives in Lebanon are discussed.

The epidemiological situation of thyroid cancer in Belarus.

Starting in 1990, an increasing number of children in regions adjacent to the site of the Chernobyl nuclear accident have been diagnosed as suffering from thyroid cancer. Using available data up to 1994, the geographical distribution, time and cohort trends, age distribution and other characteristics of this epidemic are reviewed. The results show that the geographical distribution is similar to that of iodine-131 after the nuclear accident. When looking at cohorts of children born in the same years, one can see that the incidence has been increasing steadily since 1990; deviations from this pattern might be explained by active case finding. A causal relationship with the Chernobyl accident appears the most likely interpretation of these results. Possible modifying factors should, however, be examined closely.

Childhood thyroid cancer in Belarus, Russia, and Ukraine after Chernobyl and at present

Thyroid cancer in children is usually rare, but in the individuals exposed to radiation risk of disease increases considerably. After the Chernobyl accident in 1986, an over 10-fold maximal elevation in the incidence of thyroid cancer was registered about a decade later, cumulatively resulting in more than a thousand of newly diagnosed cases in children who lived in the territories of Belarus, Russia, and Ukraine affected by radioactive fallouts. Experience from the epidemic substantially promoted knowledge in clinical pediatric oncology, pathology and basic sciences. This article overviews epidemiology, clinical features, results of treatment and follow-up of childhood patients with radiation-induced Chernobyl thyroid cancer in comparison to sporadic cases diagnosed at present. In addition, we discuss general issues of pathology and molecular findings in childhood thyroid carcinomas.

Thyroid cancer in Belarus after Chernobyl

Abstract. During 20 years after the Chernobyl catastrophe (1986–2005 inclusive) thyroid cancer was diagnosed in more than 12,000 patients of Belarus. The peak incidence in children was observed in 1995 and since 2001 only sporadic cases occur in the age group under 15 years old. In adolescents, the maximum was registered in 2001. By contrast, in the age group of 46 years or over, the current tendency is a marked increase in the number of primary thyroid cancers that dictates a correspondent intensification of special kinds of treatment. Despite a great number of patients, disease-associated mortality remains stably low; the increasing incidence indicates that thyroid malignancies have proved an actual medical problem in 5 of the 6 administrative regions of Belarus.

Childhood thyroid cancer in Belarus

The retrospective analysis was performed to compare the clinical course of radiogenic and sporadic childhood thyroid cancer. The entire series included 752 patients aged less than 15 years at diagnosis. Of them, 686 (91.2%) individuals had radiation history including 681 (90.6%) exposed at the time of the Chernobyl disaster and 5 (0.7%) children were previously treated for malignant lymphoma with an external beam therapy. The second group consisted of 66 (8.8%) unexposed patients. All the children underwent surgery and received suppressive thyroxine therapy with the mean dose of 2.0–2.5 μg/kg of body weight. Radioiodine therapy was performed in 464 (61.7%) cases. The comparison of patients with radiogenic and sporadic thyroid cancer did not reveal statistically significant differences in the distribution of tumor size, histological type or TNM stage. During follow-up time relapses were registered in 204 (27.1%) patients. The main sites of recurrence were the lung or lymph nodes whereas other lesions (thyroid remnants, the bone, soft tissues or CNS involvement) were uncommon. The disease-free survival ranged widely, 0–213 months after the date of primary surgery without significant difference between the radiogenic and sporadic cases. The observed 10-year survival was 99.5% for the entire series, including 99.5% and 99.7% in patients with radiogenic and sporadic carcinomas, respectively.

Clinical Characteristics and Future Trends of Thyroid Cancer in Belarus

Clinical Characteristics and Future Trends of Thyroid Cancer in Belarus

Breast Cancer Trends in Two Oblasts of Belarus and the Chernobyl Accident

The 1986 Chernobyl accident contaminated 23% of Belarus with radioactive iodine and long half-life radionuclides. Radiation causes breast cancer. Population-based breast cancer incidence data from the Belarus National Cancer Registry were used to study secular trends and urban-rural differences, and determine whether an effect of Chernobyl radiation exposure was discernable. Trends in age-standardized incidences in Gomel and Vitebsk oblasts maximally and minimally exposed to Chernobyl radiation, respectively, were compared for 1978-2003 among all women, and women aged 30-49, separately for urban and rural areas. Incidences were higher and increasing more rapidly in urban than rural areas of both oblasts, annually increasing 0.150 +/- 0.008 vs. 0.098 +/- 0.007 new cases per 10,000 persons, p < 0.00005. Levels were similar in urban Gomel and Vitebsk, and slightly higher in rural Vitebsk than rural Gomel. For ages 30-49 trends in urban and rural Gomel and rural Vitebsk were similar to the all-ages rural trend: common urban/rural Gomel slope 0.098 +/- 0.015, rural Vitebsk slope 0.091 +/- 0.022. In urban Vitebsk, significant but erratic nonlinearity suggested stabilizing incidence since the mid-nineties after a sharp rise. However, recent declines in slopes, greater in Vitebsk, are nonsignificant. Secular breast cancer increases in Gomel have been generally consistent for 26 years. Secular increases in Vitebsk have been similar, but could be slowing. However, these data provide no convincing evidence for Chernobyl-induced breast cancer in Belarus.

Breast cancer in Belarus and Ukraine after the Chernobyl accident

An increase in breast cancer incidence has been reported in areas of Belarus and Ukraine contaminated by the Chernobyl accident and has become an issue of public concern. The authors carried out an ecological epidemiological study to describe the spatial and temporal trends in breast cancer incidence in the most contaminated regions of Belarus and Ukraine, and to evaluate whether increases seen since 1986 correlate to radiation exposure from the Chernobyl accident. The authors investigated the trends through age-cohort-period-region analyses of district-specific incidence rates of breast cancer for Gomel and Mogilev regions of Belarus and Chernigiv, Kyiv and Zhytomir regions of Ukraine. Dose-response analyses were based on Poisson regression, using average district-specific whole body doses accumulated since the accident from external exposure and ingestion of long-lived radionuclides. The study demonstrated increases in breast cancer incidence in all areas following the Chernobyl accident, reflecting improvements in cancer diagnosis and registration. In addition, a significant 2-fold increase in risk was observed, during the period 1997-2001, in the most contaminated districts (average cumulative dose of 40.0 mSv or more) compared with the least contaminated districts (relative risk [RR] in Belarus 2.24, 95% confidence interval [CI] 1.51-3.32 and in Ukraine 1.78, 95% CI=1.08-2.93). The increase, though based on a relatively small number of cases, appeared approximately 10 years after the accident, was highest among women who were younger at the time of exposure and was observed for both localised and metastatic diseases. It is unlikely that this excess could be entirely due to the increased diagnostic activity in these areas.