Background: More than 90 % of anal cancers are caused by high-risk human papillomavirus (HR HPV) infection and a history of cervical intraepithelial neoplasia (CIN) and cervical cancer is established as possible risk factor. The aim of this study was to demonstrate relationship between anal and cervical HPV infection in women with different grades of CIN and microinvasive cervical cancer and to determinate potential risk factors for concurrent cervical-anal HPV infection. Methods: A total of 272 women were enrolled in the study. The study group included 172 women who underwent conization for high-grade CIN or microinvasive cervical cancer. The control group consisted of 100 women with non-neoplastic gynecologic diseases or biopsy- confirmed CIN 1. All participants completed a questionnaire detailing their medical history and sexual risk factors and were subjected to anal and cervical HPV genotyping using Lynear array test (Roche). Results: Cervical, anal, and concurrent cervical-anal HPV infections were detected in 82.6 %, 48.3 % and 42.4 % of women in the study group, and in 28.0 %, 26.0 % and 8.0 % of women in the control group, respectively. The prevalence of the HR HPV genotypes was higher in the study group and significantly increased with the severity of cervical lesion. Concurrent infections...

Introduction: The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal and pancreatic cancer. The first part deals with the etiological factors and the importance of polymorphisms in biotransformation enzymes and genetic alterations in the gene CHEK2 in the origin of these malignancies. In the second part, the ABC transporter genes were analyzed as potential prognostic and predictive markers of a treatment's outcome. Materials and methods: The polymorphisms and other genetic alterations were detected using real-time PCR, allelespecific PCR and PCR-RFLP methods in DNA which was extracted from the blood of patients. The frequency of polymorphisms was evaluated and their importance was assessed with regard to the available epidemiological data. Gene expressions were determined by qPCR in paired samples of tumor tissue and adjacent non-tumorous parenchyma. Results: A majority of the observed polymorphisms failed to show a relationship between their presence and the risk of any of these malignancies. CYP2A13 variant allele*7 coding inactive enzyme was found in 7 of 265 controls and in none of 235 pancreatic carcinoma patients. In contrast, GSTP1-codon 105 Val variant allele and GSTT1-null genotype were associated with an elevated...

Introduction: Colorectal cancer (CRC) is one of the most frequent malignancies and affects approximately 5% of worldwide population. More than 75% of CRC cases represent sporadic forms. Susceptibility to nonhereditary CRC is significantly influenced by polymorphisms and mutations in low-penetrance genes. Variations in biotransformation and DNA repair genes may result in acumulation of toxins and DNA damage in cells leading to the development of cancer. Furthermore, different gene expression profiles of membrane transporters affecting the accumulation of anticancer drugs in tumour cells, e.g. ABC drug transporters, may largely influence inter-individual variability in drug response and chemotherapy outcome. The aim of this study was to evaluate the role of genetic and lifestyle factors in the risk of onset and progression of colorectal cancer. This study followed selected genetic alterations in xenobiotic-metabolizing enzymes (CYP1B1, GSTM1, GSTT1, GSTP1, NQO1 and EPHX1) and genes involved in response to DNA damage (CHEK2 and NBN), as potential CRC susceptibility factors. Another aim of this study was to investigate expression profile of all human ABC transporter genes to follow their prognostic and predictive potential in colorectal carcinoma. Materials and methods: The polymorphisms and other...

<p>Vitamin D ima antiproliferativno, proapoptotsko i prodiferencijaciono dejstvo. Dokazi o dejstvu na ćelije adenokarcinoma prostate su malobrojni i nekonzistentni. Cilj ispitivanja je određivanje stepena povezanosti između nivoa vitamina D, stadijuma adenokarcinoma prostate, prostata specifičnog antigena, Gleason grade i progresije oboljenja. Ispitivanje je prospektivno, sprovedeno na 120 ispitanika (90 pacijenata sa dijagnostikovanim karcinomom prostate i 30 kontrolnih, zdravih subjekata). Pacijenti sa dijagnostikovanim adenokarcinomom prostate podeljeni su prema stadijumu bolesti u dve grupe: lokalizovano (pT2cN0M0, prostata specifični antigen &le; 20 ng/ml, Gleason 2-7) i metastatsko oboljenje (pT3-4, N1, M 0,1(a,b,c), prostata specifični antigen &ge; 20 ng/ml, Gleason &ge; 8), dok su prema ordiniranoj terapiji podeljeni u tri grupe: pacijenti koji su hemijski kastrirani, hirur&scaron;ki kastrirani i grupa kod koje je urađena radikalna prostatektomija. Uzorci za analizu nivoa vitamina D i prostata specifičnog antigen uzeti pre ordinirane terapije a nakon toga posle 6 i 12 meseci. Kako ne postoje definisane vrednosti unosa vitamina D i kalcijuma za ispitivano podneblje formirani smo Upitnik kojim smo evaluirali dnevni unos kod 90 zdravih subjekata mu&scaron;kog pola starijih od 50 godina koji nisu učestvovali u ispitivanju. Da bismo uočili ispitanike koji su hranom ili životnim navikama drastično uticali na vrednost vitamina D isti Upitnik su ispunili svi ispitanici uključeni u ispitivanje. Ustanovljena je očuvana godi&scaron;nja oscilacija vitamina D kod ispitanika te smo statističkim modelom korigovali ovu varijablu. Rezultati pokazuju da grupa obolelih nema apsolutno niske vrednosti vitamina D i da su vrednosti kod obolelih niže u odnosu na kontrolne subjekte (64.12 nmol/l vs. 74.45 nmol/l). Nije uočena razlika u nivou vitamina D kod pacijenata sa lokalizovanim i metastatskim oboljenjem (62.90 nmol/l vs. 64,65 nmol/l). Odnos između prostata specifičnog antigena i vitamina D posmatran tokom perioda ispitivanja pokazuje da je kod obolelih pacijenata koji su hemijski ili hirur&scaron;ki kastrirani i kod pacijenata kod kojih je urađena radikalna prostektomija postoji pozitivna korelacija pre ordinirane terapije u sve tri grupe, nakon ordinirane terapije možemo uočiti inverznu korelaciju. Konrolna grupa ispitanika pokazuje stalnu pozitivnu korelaciju između nivoa vitamina D i prostata specifičnog antigena. Pacijenti kod kojih je do&scaron;lo do progresije imaju niže vrednosti nivoa vitamina D u odnosu na pacijente kod kojih nije do&scaron;lo do progresije. Nije ustanovljena korelacija između vremenskog intervala do progresije oboljenja i nivoa vitamina D.</p> / <p>Vitamin D has antiproliferative, proapoptotic and prodifferentiational actions. There is a limited number of studies asessing influence of vitamin D on prostate cancer. Results of those available studies are inconsistent. This study hypothesizes with correlation of vitamin D, prostate cancer stage, prostate specific antigen, Gleason grade, stage, and disease progression. This prospective study included 120 subjects (90 subjects with diagnosed prostate cancer and 30 healthy, age adjusted controls). Patients with diagnosed prostate cancer formed two groups by criterion of disease advancement: localized (&le;pT2cN0M0, prostate specific antigen &le; 20 ng/ml, Gleason 2-7) and metastatic (&ge;pT3-4, N1, M 0,1(a,b,c), prostate specific antigen &ge; 20 ng/ml, Gleason &ge; 8. According to applied therapy subjects were devided in three groups: surgicaly castrated, medicamentous castrated and radical prostatectomy treated. Samples were obtained before therapy and after 6 and 12 months. As no defined value for vitamin D and calcium intake could be found we formed Questionnaire for vitamin D and calcium intake. Data were obtained from 90 healthy, age adjusted subjects, not included in this study. All subjects included in this study filed the Questionnarie and subjects with unusual vitamin D and calcium intake were excluded. Annual oscilation of vitamin D was observed, so we applied statistical model that excluded this variable. Subjects with diagnosed prostate cancer didn&#39;t have absolutely low vitamin D level. This level was lower in group of subjects whith diagnosed prostate cancer comparing to controls (64.12 nmol/l vs. 74.45 nmol/l). No differences in vitamin D level was observed in groups of patients with localised and metastatic disease (62.90 nmol/l vs. 64,65 nmol/l).<br />Correlation of vitamin D and prostate specific antigen during 12 months period showed that castrated subjects and subjects in radical prostatectomy group showed possitive correlation before surgical treatment and inverse, negative correlation, after treatment. Control group showed possitive correlation of vitamin D and prostate specific antigen in all three measurements. Subjects with progression have significantly lower vitamin D level comparing to subjects without progression. No correlation between time to progression and vitamin D have been observed.</p>

Chronic pancreatitis is considered a risk factor for pancreatic cancer. An exact mechanism how chronic inflammation of the pancreas leads to pancreatic cancer is not yet understood; the possibility of a shared genetic predisposition for both diseases is also assumed. A similar association in patients with AIP has not yet been demonstrated. The aim of our work was to expand the knowledge about relationship between chronic pancreatitis and pancreatic cancer. We studied the association of the diseases in two synchronous projects. In the first one, we examined the occurrence of pancreatic cancer in patients with autoimmune pancreatitis. In the second project, we investigated the presence of genetics variants associated with chronic pancreatitis in patients with pancreatic cancer. In the retrospective study of our cohort of patients, we were one of the very first in the world to show occurrence of pancreatic cancer in patients with autoimmune pancreatitis, and as the only one, we have defined the characteristics of such patients. To assess the association of the diseases, we performed a systematic review where we identified all reported cases of coincidence of pancreatic cancer and autoimmune pancreatitis; the incidence of cancer in patients with autoimmune pancreatitis was similar to that of patients...

Breast cancer is the most common tumor disease diagnosed in women worldwide. The hereditary character of this disease is observed in 5-10 % of all cases, and it is usually caused by a pathogenic mutation in one of the predisposition genes. Although a variety of pathogenic mutations in the coding sequences of these genes was described, the cause of the disease is still unknown in many familial cases (> 50%). A great number of identified pathogenic mutations were localized in the consensus splicing sites, which results in the formation of aberrant mRNA splicing variants and their damaged protein isoforms. However, little is known about mutations affecting regulatory splicing sites, which can result in the translation of similarly affected mRNAs. In this work, we proposed a method for indirect detection of mutations affecting the natural splicing pattern of any gene of our interest based on multiplex PCR and NGS with high sensitivity. Verification of this method on the BRCA1 model gene revealed the presence of the total of 94 splicing variants in peripheral leucocytes and healthy breast and adjacent fat tissues. This is the most detailed catalogue of physically occurring BRCA1 mRNA variants thus far. The most commonly occurring variants, maintaining open reading frame, were quantified by RT-qPCR which...

Thyroid nodules represent a very common pathology. Using modern high-resolution ultrasound, nodules could be found in up to 68 % of patients. The most important task is the diagnosis of thyroid cancer which represents only about 5-15 % of nodules, however the incidence is still growing. Even with the use of a fine needle aspiration biopsy, it is not always possible to decide on the biological nature of the nodule. A significant proportion of such patients have to undergo thyroid surgery for diagnostic reason. Thyroid surgery is associated with risks to the patient and financial costs to the health-care system. In recent decades, the efforts to improve non-invasive diagnostics of thyroid nodules have been made. The thyroid elastography and thyroid autoimmunity are among the examined risk parameters. Using real-time strain elastography, thyroid carcinomas elasticity has been significantly reduced compared to benign thyroid nodules in our group of patients. The elastography of thyroid nodules can be used as a suitable complement to conventional sonographic examination. In our work, the combination of both methods (conventional ultrasound and elastography) increased the negative predictive value compared to both methods individually. The results of our work further indicate that, in case of absence of...

Chemotherapy is one of the basic therapeutic procedures of breast cancer (BC) which may precede and/or follow the surgical resection of a tumor as a part of neoadjuvant or adjuvant therapy. However, the selective pressure of chemotherapy on tumor cells may change their molecular and expression profile and thus also their chemosensitivity. The aim of our work was to document the expression changes of selected markers in BC after neoadjuvant chemotherapy, which may contribute to the understanding of the role of these proteins and genes in tumor response to chemotherapy and the development of chemoresistance. Immunohistochemical analysis of expression of standard BC markers [estrogen (ER) and progesterone receptors (PR), HER2 and proliferation activity (Ki67)] and intercellular junction proteins (claudin 1, 3 and 4, E- and N-cadherin) before and after neoadjuvant chemotherapy revealed a decrease of PR, Ki67 and claudin 3 expression and an increase of claudin 1 expression. The expression of ER, HER2, claudin 4, E- and N-cadherin proved to be stable. Assessment of standard BC markers is performed routinely during a bioptic investigation as a necessary factor for therapy indication. Our results support the current recommendations for the re-examination before indication of adjuvant chemotherapy. Claudins...

Introduction: About 5 - 10% of breast carcinomas are caused by genetic mutations. The most common genetic mutation that is involved in the development of this malignancy is a mutation in the tumor suppressor genes BRCA1/2 whose carriers have approximately a 70% lifetime risk of developing breast cancer. The prognosis of patients with BRCA1/2-asociated breast carcinoma, compared to patients with sporadic breast carcinoma is the subject of many studies with ambiguous results. Aim: The aim of the theoretical part of this work was to approach the issue of breast cancer and the most common genetic syndromes associated with it. In the practical part of this work a retrospective study was carried out in order to compare BRCA1/2 mutated breast cancer patients with non-mutated breast cancer patients in the tumor profile, methods of treatment and prognosis. Methods: We retrospectively analyzed the data of 134 patients who were tested for the presence of BRCA1/2 mutation at the Institute of Medical Genetics, University Hospital in Pilsen during the years 2013-2018 and at the same time were treated for early breast cancer at the University Hospital in Pilsen during the years 2000-2020. 32 patients were BRCA1 positive (24%), 10 BRCA2 positive (7%) and 92 without BRCA1/2 mutation (69%). The follow- up time was...

The Ph.D. thesis is a collection of eleven commented articles on the topic of molecular-genetic profiling of urogenital tract tumors published in impact factor journals. In the introduction the origin and development of classification units is described including a brief overview of recent genetic profiles of selected types of renal carcinomas. Reviewed are major signaling pathways exploited in targeted therapy as well as the function of the corresponding drugs. Directions in which the research of new biomarkers is aimed are mentioned and the introduction ends with a short list of molecular genetic methods used in classification of renal carcinomas. In the results section are summarized the most important morphological, immunohistochemical, and molecular genetic findings of the studied sets of renal carcinomas. The data are compared with the present characteristics of known entities and hypotheses of possible new entities or relations between them are inferred. In the conclusions the suitability and limitations of the used molecular genetic methods are discussed in the context of the difficulties of the material analyzed and the designs of the studies.