Bulgarian Population Research Articles

Epidermal growth factor receptor mutations in East European non-small cell lung cancer patients.

Epidermal growth factor receptor (EGFR) gene mutations are recurrently observed in non-small cell lung carcinomas (NSCLCs), and it has been found that they may serve as specific therapeutic targets. The aim of the present study was to determine the prevalence of EGFR gene mutations in NSCLCs in an East European (Bulgarian) population in different histological subtypes, in cytological versus histological samples and in primary versus metastatic lesions. In this study 1427 NSCLC samples were included. DNA was extracted from either formalin-fixed paraffin embedded (FFPE) tissues or cytology specimens and analyzed for the presence of 29 recurrent EGFR gene mutations using SARMS PCR. EGFR gene mutations were found to occur significantly more often in female than in male patients (19.4% vs. 5.4%; p<0.001), in adenocarcinomas than in squamous cell carcinomas or other histological subtypes (12.5% vs. 6.2%, and 7.6%, respectively; p=0.009), and in never smokers than in ex-smokers and current smokers (22.9% vs. 8.5% and 4.9%, respectively; p<0.001). No significant differences were observed in the occurrence of EGFR gene mutations in primary tumors compared to metastases (7.9% vs. 11.2%; p=0.092), or in FFPE samples compared to cytological samples (8.9% vs. 8.1%; p=0.813). Our data show that the overall frequency of EGFR gene mutations in lung adenocarcinomas in the East European cohort studied is within the range of that observed in North American and West European populations, but that its frequency in squamous cell carcinomas is higher than that in any population reported to date. All specimens appeared to be suitable for EGFR gene mutation analysis, irrespective nature or origin.

Sun protection habits and ocular UV damage of the Bulgarian population, first results using the method of conjunctival ultraviolet fluorescence

The purpose of this study is to present our first data and impressions of the sun protection habits and conjunctival ultraviolet autofluorescence (UVAF) of a randomly selected target group. Materials and Methods : A prospective, randomized study, including photographs of 123 subjects (246 eyes) and 200 questionnaires. Subsequently UV photography based on autofluorecence was used. For each eye three pictures were taken - eye in first position, temporal gaze (documenting nasal part of the limbus) and nasal gaze (documenting temporal part of the limbus). Results : Results are based on the study of 123 subjects (246 eyes). The participants in the study were aged between 5 and 88 years (average age=39). 87% of the surveyed believe that there is a risk of UV damage only in the summer. A significant percentage (55%) do not pay attention to the special protective equipment such as umbrellas and caps. Photography results were analyzed with specialized software and showed that 83 participants (67.48%) have conjunctival autofluorescence, as women prevail (women n=47 persons, men n=36 persons). The area of conjunctival UVAF tends to increase with age. No correlation between intensive sun exposure (resp. UV radiation) and a sharp increase in the dimensions of the UVAF zone is established, suggesting a chronic damage, in support of which is the demonstrative eye damage in people with high-risk occupations (associated with electric welding, lifeguards and other outdoor occupations). Conclusions : We suggested that the area and the intensity of UVAF increases with age, and probably corresponds only to a chronic damage. The degree of damage correlates to a large extent to the bad sun protection habits demonstrated in the questionnaire.

Patient Attitudes and Patterns of Self-Medication with Antibiotics – A Cross-Sectional Study in Bulgaria

BACKGROUND: Self-medication with antibiotics is a major concern worldwide because of the high risks of antimicrobial resistance which may result in complicated courses of treatment, increased risk of death and excess costs to the healthcare systems. AIM: The aim was to study the attitudes and self-medication patterns as related to the use of antibiotics among the general Bulgarian population and their determinants. MATERIALS AND METHODS: A questionnaire-based survey was performed among the patients in two randomly selected municipalities. The questionnaire was mailed to 50 randomly selected adult patients by each of the 33 responding GPs thus addressing a total of 1650 participants. RESULTS: A total of 1050 patients completed and returned the questionnaire. The observed self- medication rate was 43%. The women and the younger employees and students tended to have a higher self-medication rate. Fever (22%), sore throat and cough (12.7%) and discomfort when urinating (8.2%) were the most frequent patterns related to the practice of self-medication. CONCLUSION: This analysis reported an extensive use of self-medication with antibiotics in the study population before the changes in the Bulgarian legislation. Younger age and social status (students, employed) were the most important socio-demographic patterns that had probably led towards self-medication with antibiotics.

Patient Attitudes and Patterns of Self-Medication with Antibiotics – A Cross-Sectional Study in Bulgaria

BACKGROUND: Self-medication with antibiotics is a major concern worldwide because of the high risks of antimicrobial resistance which may result in complicated courses of treatment, increased risk of death and excess costs to the healthcare systems.AIM: The aim was to study the attitudes and self-medication patterns as related to the use of antibiotics among the general Bulgarian population and their determinants.MATERIALS AND METHODS: A questionnaire-based survey was performed among the patients in two randomly selected municipalities. The questionnaire was mailed to 50 randomly selected adult patients by each of the 33 responding GPs thus addressing a total of 1650 participants.RESULTS: A total of 1050 patients completed and returned the questionnaire. The observed self-medication rate was 43%. The women and the younger employees and students tended to have a higher self-medication rate. Fever (22%), sore throat and cough (12.7%) and discomfort when urinating (8.2%) were the most frequent patterns related to the practice of self-medication.CONCLUSION: This analysis reported an extensive use of self-medication with antibiotics in the study population before the changes in the Bulgarian legislation. Younger age and social status (students, employed) were the most important socio-demographic patterns that had probably led towards self-medication with antibiotics.

The relationship between apolipoprotein B/ apolipoprotein A1 ratio, high sensitivity C - reactive protein and some components of metabolic syndrome in Bulgarian population

The relationship between apolipoprotein B/ apolipoprotein A1 ratio, high sensitivity C - reactive protein and some components of metabolic syndrome in Bulgarian population

Association of single nucleotide polymorphism at position −308 of the tumor necrosis factor-alpha gene with ankylosing spondylitis and rheumatoid arthritis

In this study, we analyzed the putative association between the −308 G/A polymorphism in the promoter region of the tumor necrosis factor (TNF) α gene (rs1800629) and chronic inflammatory arthritis in the Bulgarian population. A case-control study was carried out on 58 patients with ankylosing spondylitis (AS), 108 rheumatoid arthritis (RA) patients and 177 healthy subjects. −308 G/A TNF-α genotypes of patients and controls were determined by restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR). No significant association between the rs1800629 polymorphism and RA risk in the study cohort was observed. However, there were significant differences in the genotype and allele frequencies of the −308 G/A TNF-α polymorphism between AS patients and the healthy subjects. In logistic regression analysis, the presence of the TNF-α −308A allele in the genotype (AA + AG vs. GG) was associated with a 3.298 times lower risk of developing AS. In addition, in AS, there were associations for age at disease onset (<29 years; odds ratio (OR) = 0.222), disease severity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score > 4; OR = 0.152) and response to anti-TNF treatment (OR = 2.25) under a dominant model (AA + AG vs. GG). In conclusion, our results suggested that the promoter polymorphism −308 G/A in the TNF-α gene had no significant effect on RA development, but could play a role in AS development and in determining the age of disease onset, disease severity and therapeutic outcome of AS in the Bulgarian patients who participated in our study.

Association of rs172378 C1q gene cluster polymorphism with lupus nephritis in Bulgarian patients.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease that can affect substantially any organ in the body. One of its most severe manifestations is lupus nephritis. Hereditary C1q deficiency is strongly related to SLE but there are very few and inconsistent studies exploring the single nucleotide polymorphisms (SNPs) of the C1q gene cluster in relation to the pathogenesis of SLE. In the present study we evaluated the possible association of gene variants in complement C1q gene cluster with susceptibility to lupus nephritis in a Bulgarian population, focusing on five previously associated with SLE SNPs in other populations. Thirty-eight patients with lupus nephritis and 185 healthy controls, all from Bulgaria, were genotyped for the five C1q SNPs, rs587585, rs292001, rs172378, rs294179 and rs631090, by quantitive real-time PCR methods. We also determined C1q serum levels of C1q and haemolytic activity of C1q in relation to C1q genotypes. Lupus nephritis patients and healthy controls had statistically similar frequencies of genotypes and alleles of rs587585, rs292001, rs294179 and rs631090 SNPs. Nevertheless, minor G allele in rs172378 was significantly overrepresented in lupus nephritis patients when compared with healthy controls (36% vs. 23%, odds ratio = 1.80, 95% confidence interval = 1.06-3.06, p = 0.029). The SNP rs292001 showed a trend towards lower serum C1q levels in healthy controls. Two SNPs - rs294179 and rs292001 - were in a linkage disequilibrium in patients and healthy controls with different power (healthy controls: r (2 )= 0.6526, D' = 0.842; lupus nephritis patients: r (2 )= 0.491, D' = 0.686). The haplotype C-A-A-T-T in the patient group was associated with lupus nephritis: 7.7% vs. 0.8%, odds ratio = 10.81, 95% confidence interval = 1.45-80.57, p = 0.002. These results support the implication of the G allele in rs172378 as a risk factor for lupus nephritis in a homozygous status, at least for a Bulgarian population.

Winter 25-hydroxyvitamin D levels in young urban adults are affected by smoking, body mass index and educational level.

To study the relationship of winter 25-hydroxycholecalciferol (25-OHD) levels with age, education, place of residency, marital status and body mass index (BMI) as they may affect sun exposure, vitamin D synthesis and metabolism. Subjects (1952) answered a structured questionnaire concerning education, marital status and smoking; and body weight/height, and parathyroid hormone and 25-OHD were measured. 25-OHD levels were higher in the males with elementary and secondary education compared with higher education (46.8±18.5 and 43.7±16 vs 39.9±15.3 nmol/l, P<0.01). Vitamin D deficiency was more prevalent (16.7%, (13.1-20.2) vs 10.8%, (8.4-13.2), P=0.08) and sufficiency was less prevalent (24.6% (20-29.2) vs 33.7%, (29.5-37.8), P=0.005) in those with higher than secondary education. No differences were found among the females. Male smokers had lower 25-OHD than nonsmokers (40.2±16.6 vs 43.6±15.7 nmol/l, P=0.004). Deficiency was more prevalent in the male smokers than nonsmokers with secondary and higher education (secondary 16.6%, (10.1-22.4) vs 8.2%, (5.1-11.3), P=0.006; higher 27.4%, (17.7-37.1) vs 13.2%, (9.0-17.5), P=0.003). 25-OHD was lower in the obese than in the normal-weight females (34.6±16.2 vs 38.2±17.8 nmol/l, analysis of variance, P=0.014), but not males. Marital status was not related to 25-OHD. Only in the urban residents, increasing BMI in the young females increased the risk for vitamin D deficiency by 1%, and smoking had an odds ratio of 1.99 (1.05-3.78) in the young and 2.5 (1.07-5.75) in the middle-aged males. Smoking and higher education in the males and obesity in the females were factors for vitamin D deficiency among Bulgarian urban population.

Sub-species diversity of Xanthomonas euvesicatoria Bulgarian and Macedonian strains from pepper

Sub-species diversity of pepper populations of Xanthomonas euvesicatoria in Bulgaria and Macedonia in 2012 was the object of this study. Species determination of 44 strains was performed by molecular methods using two pairs of species-specific primers and RFLP (restriction fragment length polymorphism) analysis of the 16S-23S ITS region with HpaII. The populations were characterized by genotypic and phenotypic properties. The genotypic diversity of the strains was evaluated by RAPD (random amplified polymorphic DNA) technique. Primer CUGEA-6 differentiated the strains in two groups, one of which included only Bulgarian strains and revealed a mixed profile of the type strain. BiologTM metabolite profiles separated the strains in four groups: two of which were composed only of Bulgarian or Macedonian strains. Correlation between the RAPD and the metabolic profiles was observed. Twelve antibiotics and copper ions in five concentrations (1–5 g kg−1) were tested for biological activity. The inhibition zones of the Bulgarian strains were statistically proven to be considerably larger than the Macedonian ones in the tests with kanamycin, streptomycin, polymyxin B sulphate, tetracycline and vankomycin. The inhibition zones of the Bulgarian strains were statistically proven to be relatively larger than the Macedonian ones in the copper tests. Based on our studies the Macedonian population of X. euvesicatoria manifested a relative homogeneity while a greater diversity was observed in the Bulgarian population.

Determinants of normal macular and retinal nerve fiber layer thickness measured by 3d Oct 2000 - Topcon

PURPOSE : To generate the normative data of macular and retinal nerve fiber layer thickness for Bulgarian population using 3D OCT 2000 – Topcon and to evaluate the effects of gender and age on these parameters. MATERIALS AND METHODS : The 131 eyes of 67 healthy individuals aged between 16-71 years, with no ocular disease and best corrected visual acuity of 20/20, were examined using standard scanning protocols. The mean macular and RNFL thickness were evaluated, and the effects of age and gender on these parameters were analyzed. RESULTS : The mean retinal thickness (RT) was 275.4±11.59μm, mean central foveal thickness (CFT) was 241.8±2.01μm, mean central point thickness (CPT) was 213.7±28.64μm. The macular thickness was lowest at the fovea and maximal at the superior inner macula (308.7±13.6 μm). The mean retinal nerve fiber layer (RNFL) thickness was 109.44±9.73μm. The RNFL was thickest in the inferior quadrant (136.13±17.70μm). There was negative but insignificant correlation between macular thickness and volume, and age. The RNFL thickness showed significant negative correlation with age (p=0.03). CFT in females was significantly thinner than in males (p=0.01). CONCLUSIONS : Our findings provide basic data to facilitate macular and RNFL thickness analysis using 3D OCT- 2000. The normative database is important for early diagnosis and evaluation of pathological changes in various retinal diseases and glaucoma. Our results indicate that age and gender must be considered while interpreting macular retinal thickness data.

AB0076 Promoter IL12B Gene Polymorphism Contributes to Rheumatoid Arthritis Development

BackgroundIL12B encodes the IL-12p40 subunit of both the IL-12 and IL-23 cytokines, which play critical and unique roles in bridging the innate and adaptive immune systems. Whereas IL-12 induces development...

Potential statin-drug interactions: prevalence and clinical significance.

BackgroundStatins are cholesterol-lowering drugs widely used for cardiovascular prevention. Although safe when used alone, in combination with other drugs the likelihood of adverse drug reactions increases significantly. The exposure of the Bulgarian population to coprescriptions leading to potential statin-drug interactions is currently unknown.ObjectiveThe aim of this study was to investigate the incidence of coprescriptions involving statins and to compare the exposure of outpatients and inpatients to potential statin-drug interactions.SettingA cardiology clinic of the teaching University hospital in Varna, Bulgaria.MethodThis observational retrospective study examined the medical records of hospitalized patients prescribed a statin in combination with potentially interacting drugs. Patients who entered the hospital with a statin coprescription (considered outpatients) were compared with those coprescribed a statin at discharge from hospital (considered inpatients). Potentially interacting drugs included inhibitors and inducers of cytochrome P450 (CYP) enzymes and drugs of narrow safety margin (coumarin anticoagulants, digitalis).Main outcome measureThe proportion of patients exposed to statin coprescriptions with potentially interacting drugs at hospital admission and discharge. Secondary outcome measures: laboratory evidence supporting possible statin-drug interactions.ResultsOut of 1641 hospitalized patients examined, 572 were prescribed a statin, either at hospital admission or discharge. Simvastatin was most commonly prescribed and simvastatin-drug coprescription predominated, especially at discharge. The exposure to all potential statin-drug interactions was similar at hospital admission (26.1%) and discharge (24.4%), as was the exposure to statin combinations with CYP inhibitors, 6.4% and 4%, correspondingly. Overall, more coprescriptions were generated, than were eliminated by hospital physicians. Amiodarone was the CYP inhibitor most frequently coprescribed. Of all interacting drugs acenocoumarol was the most commonly found, the proportions of statin-acenocoumarol coprescriptions being roughly the same at hospital entry (11.5%) and discharge (12.4%). In 7 patients out of 69 exposed to the combination, INR was found to be higher than 3, indicating a risk of over-anticoagulation.ConclusionsPotential statin-drug interactions are common. Although they do not differ between outpatient and inpatient settings, new hazardous coprescriptions are more frequently generated in hospital. Caution is required when acenocoumarol is coprescribed with statins, especially simvastatin.

Maximizing affluence within the planetary boundaries

Ordinary product LCA studies focus on measuring or minimizing environmental impact, but do not address if the product fits in a sustainable consumption pattern. This paper proposes a setup in which the planetary boundaries define the maximum impact, and the minimum requirements for a reasonable consumption level specify a lower impact level. Thus, a “safe operating space” remains. We use an IO table for EU-27 and the consumption pattern of the Bulgarian population extrapolated to the EU level as driving climate impact. The EU’s policy targets are used as a planetary boundary for climate change. The 2020 target is shown to be able to accommodate the Bulgarian-style consumption, with room for a much higher GDP. The 2050 target, however, is too narrow, and a slightly smaller consumption pattern is needed to reach the target. Although the approach is highly simplified and neglects many developments, the idea of using IO-tables and minimum consumption levels to backcast directions to be taken is expected to help policymakers. We acknowledge some important limitations of our approach, but accept these in the context of exploring future scenarios and how to get there, instead of predicting the future.

Frequency of Primary Torsion Dystonia for the Population of Bulgaria – A Service-Based Survey

Background: According to the majority of epidemiological studies for primary torsion dystonia (PTD), it is a rare disease, although there are some controversial data, showing much higher figures. Because the need of clarification in this field, the aim of this study is to estimate the frequency of primary torsion dystonia in the Bulgarian population. Materials and Methods: We made an official inquiry to the National Center for Health Information, and to the National Health-Insurance Fund for the total count of all the patients, registered with the diagnose of PTD for a period of a year. Simultaneously we examined the archive of the University Multidisciplinary Hospital for Active Treatment of Neurology and Psychiatry - UMHATNP “St. Naum” in Sofia, with a specialized department of Movement Disorders, for the period of 01.01.2008-01.01.2012. Results: Crude annual prevalence of primary torsion dystonia estimated in this study is significantly lower than most reported epidemiological findings on prevalence. Probably the actual prevalence is higher than that calculated in the current study, but this could be demonstrated by improving the collection of data and methods for screening and diagnosis. Conclusions: The downside of this study, as with most studies in this area worldwide, is that it is based on the demand of medical care. Thus remain not estimated all undiagnosed and and incorrectly diagnosed cases and patients that have not sought medical attention. The majority of the patients in our sample came from the South-Western Region of the country. According to distribution by form of dystonia, age, gender and time to diagnose our results with some exceptions are similar to those, reported in the literature.

Next-generation sequencing of BRCA1 and BRCA2 in breast cancer patients and control subjects

Breast cancer is currently the most common type of cancer in females. The majority of the hereditary forms of breast cancer are caused by mutations in the BRCA1 and BRCA2 genes, whose main function is the DNA repair of double-strand breaks. Genetic testing of females with a family history of breast cancer is recommended to determine their hereditary predisposition for this type of cancer. The variants with no clear clinical significance may represent a diagnostic challenge when performing targeted resequencing. In this study, DNA samples were obtained from 24 breast cancer patients (mean age, 35±10 years) with a positive family history and from 71 age-matched healthy controls. Informed consent was obtained from all the subjects. Sequence-targeted BRCA1 and BRCA2 libraries were prepared using the TruSeq Custom Amplicon method and sequenced on the Illumina MiSeq system. A wide range of variants were identified in the BRCA1 and BRCA2 genes. Two pathological/presumably pathological variants were detected in the breast cancer patient group: a mutation in BRCA2 at the chromosomal (chr) position chr13:32890665, which affected the first position of the 5' splice region following exon 2; and a mutation in BRCA1 at chr17:41219635, causing an in-frame triple nucleotide deletion of valine 1688 (8.3%). In the patient and control groups, 7 likely polymorphic variants and 13 common variants were detected in the BRCA1 and BRCA2 genes. To the best of our knowledge, this study was the first to identify 3 common polymorphisms in BRCA2, characteristic solely of the Bulgarian population, including chr13:32973737, T/-, a single-nucleotide polymorphism (SNP) within the 3'-UTR of exon 27; chr13:32973280, A/-, a mononucleotide deletion within the 5'-UTR of exon 27; and chr13:32973924, T/-, a mononucleotide deletion downstream of the gene sequence. To the best of our knowledge, this study was the first to apply next-generation sequencing of the BRCA1 and BRCA2 genes in a Bulgarian population, prompting further investigation for local founder mutations and variants characteristic for this particular region.

Survival rate and mortality of juvenile and immature eastern imperial eagles (Aquila heliaca) from Bulgaria studied by satellite telemetry

Abstract A long-living species like A. heliaca has a natal dispersal period lasting several years. This period is crucial for the survival and conservation of the eagles. In this study we present mortality factors and the survival rate of juvenile and immature A. heliaca from Bulgaria as established by satellite telemetry. A total of 20 juvenile A. heliaca were fitted with GPS/Argos transmitters in their nests in Bulgaria. Fourteen birds were tracked till their death and the bodies were found. Tracking allows the survival rate of juvenile and immature A. heliaca to be estimated for the first time. It is 59.1% for the first calendar year, 83.3% for the second calendar year and 80.0% for the third calendar year. The main mortality factor for juvenile and immature A. heliaca from the Bulgarian population is electrocution, which caused 59.0% of the mortality cases. Other threats identified are shooting, poisoning and collisions. Most of the fatalities of these tracked eagles occurred in Bulgaria (50%) and Turkey (43%). Thus, Turkey is a key country for conservation of the Bulgarian population ofA. heliaca during its dispersal period. Eagles from Bulgaria have been recorded dispersing further south, to Sudan and Saudi Arabia. Conservation efforts are needed both inside and outside Bulgaria in order to reduce mortality. International collaboration and the exchange of experiences should be part of any conservation strategy or plans focused on the eastern imperial eagle.

Serum hepcidin levels in Bulgarian population.

Hepcidin is a 25-aminoacid cysteine-rich iron regulating peptide. Hepcidin quantification in human serum provides new insights for the pathogenesis of disorders of iron homeostasis. This study describes an ELISA immunoassay for hepcidin quantification in human serum and reference ranges for Bulgarian population. We used a sandwich ELISA method from USCN Life Science inc. that consists of ready to use, pre-coated 96-well strip plate with 2 antihepcidin-25 monoclonal antibodies. A recombinant Hepcidin in 16 μg/L concentration is used as a standard. We correlated ELISA results of hepcidin-25 measurements in healthy population to ferritin, hemoglobin concentration in reticulocytes, transferrin, and iron levels. The sandwich ELISA was highly specific for hepcidin-25. We found that serum hepcidin levels for Bulgarian population are 3.052 μg/L - 37.750 μg/L, which is quite similar to that established by WCX-TOF MS from the Laboratory of Genetic, Endocrine and Metabolic Diseases; Dept. of Laboratory Medicine, Radbound University Medical Centre; Nijmegen, The Netherlands. Ferritin levels and hemoglobin concentration in reticulocytes correlated significantly to serum hepcidin levels (0.3 < r < 0.5, p < 0.010). Transferrin levels showed negative and no significant correlation to hepcidin in serum (r = -0.111). The use of two monoclonal antibodies in a sandwich ELISA format provides a reliable, reproducible, and not very expensive method for measuring serum concentrations of the bioactive form of hepcidin in Bulgarian laboratory practice.

Dried Fruits – Brief Characteristics of their Nutritional Values. Author’s Own Data for Dietary Fibers Content

A review of nutritional and dietetic properties of dried fruits, such as natural and concentrated sources of sugars, vitamins A, C, niacin, riboflavin and folate, potassium and trace elements of iron and copper, and of organic acids, phytonutrients with antioxidant properties was made. Many important properties of dry fruits have a low glycemic index and the content of dietary fiber, including insoluble fiber. The results of insoluble dietary fiber content by enzymatic-gravimetric method AOAC 991.42 of 18 kinds of different varieties Bulgarian dried fruits were shown. The highest content of fiber was found in hips (40%), followed by dried quinces, pears, chokeberries, dried apples, and plums (from about 13% to over 23%). A lower content of insoluble fiber in different varieties of cherries and sour cherries is established. The data are important for a healthy nutrition of Bulgarian population, but also for a diet-therapeutic practice, and problems related to motility of the gastrointestinal system, anemia, and atherosclerosis, cardiovascular and metabolic diseases.

“Idea zrodzona z rozpaczy“. Rola ruchu unickiego w bułgarskim odrodzeniu narodowym

The article describes problems connected with the idea of a cooperation between Orthodox Bulgarian population and the Catholic Church at the turn of 50s and 60s of 19th century. The Uniate Movement was founded by Dragan Tsankov, who started to propagate the idea of westernization of Bulgarians in the newspaper “Balgariya” with the cooperation with the French missionaries from the Congregation of the Mission and the Polish emigrants from the Hotel Lambert. The milieu of Dragan Tsankov firstly supported the Union in Kukush in 1859 and one year later leaded to the nationwide Union. These events played an important role in history of the Bulgarian Revival and development of the Church Movement. It contributed to the emergence of the Bulgarian exarchate (1870), which was a decisive step for the Bulgarian fight for political rights in the Ottoman Empire.

Study of the Carrier State for Five BRCA1/BRCA2 Deleterious Mutations in Bulgarian Women with Breast Cancer

Summary Genetic testing for BRCA 1/2 mutation is a well recognized medical management tool. Identification of healthy carriers of such mutations allows effective risk reduction procedures to be performed. There is no data reported on the founder mutations in the Bulgarian population. To evaluate the contribution of genetic factors to breast cancer (BC), we investigated the carrier state of Bulgarian women with BC for five common (according to BIC database) deleterious BRCA1/2 mutations. The list of patients diagnosed with BC between January 2011 and April 2012 was obtained from the Cancer Registry of University Hospital, Pleven. Eighty-two women with BC were interviewed and a pedigree was constructed of each of them. The patients were classified into seven categories, according to personal, disease and family history. Based on the preliminary prepared selection criteria and the personal family history, we defined a target group of 33 Bulgarian women with BC. They were screened for five deleterious mutations: 5382insC in BRCA1 and 6174delT, 6079del4, 8138del5, 5946delCT in BRCA2, by DNA sequencing. The genetic analysis detected none of the tested mutations. Two polymorphic variants were found in BRCA2 gene: c.5744C&gt;T (rs4987117, SNP database) in exonl 1E in one patient and c.7806-14T&gt;C (rs9534262, SNP database) in exonl7 in 22 patients. In conclusion, without basic information on the founder mutations in the population, the genetic screening for the specific mutations in a small group of tested patients is ineffective.