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Role of the FTO gene in the genetic determination of common multifactorial diseases
Dlouhá, Dana ; Hubáček, Jaroslav (advisor) ; Černá, Marie (referee) ; Rossmeislová, Lenka (referee)
Obesity is a risk factor for development of cardiovascular disease, diabetes type 2 and some cancers. Newly detected genetic risk factor for body weight is the FTO gene ("fat mass and obesity associated"). The aim of this thesis was determine 1) whether the presence of risk alleles correlate with BMI in Czech population and to determine 2) whether there is an association between variants in the FTO gene and risk of myocardial infarction/ acute coronary syndrome (MI/ ACS), 3) renal failure (ESRD), or 4) incidence of colorectal cancer (CRC). We analyzed polymorphisms rs17817449 (first intron) and rs17818902 (3rd intron) using by PCR-RFLP and then also RT PCR. We found an association of the first intron variant (but not the 3rd one) and BMI in Czech control population. We have detected an association of 1st intron SNP and BMI changes during the intervention study in obese children, but not in obese females. We found a correlation between the risk allele and increased risk of ACS (OR 1.49) in patients with MI. In patients with ESRD was detected association between the risk allele and the risk of disease (OR 1.37). We didn't confirmed the association between rs17817449 and the development of CRC. Representative selected groups of the Czech populations "MONICA" and "HAPPIE" were used as controls. One...
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Diagnosis of Lynch syndrome based on pathologic examination
KRAUSOVÁ, Lenka
Lynch syndrome is an autosomal dominant disease predisposing to cancer development. Up to 5 % of colorectal cancers may be associated with Lynch syndrome. Due to its familial occurrence the diagnosis is important for family screening. Currently it is based on methods of modern pathology. Theoretical part describes structure of gastrointestinal tract, definition and history of Lynch syndrome, and methods of its laboratory diagnostics. The diagnosis can be based on evaluation of tumor microscopical features (Semi PREDICT score) in tissue sections, imunohistochemical investigation of MMR (mismatch repair) proteins, or molecular genetic MSI (microsatellite instability) testing. Practical part focuses mainly on correlation of immunohistochemistry and MSI testing. Randomly selected cases of colorectal cancer were organized into 2 study groups. The first group consisted of 25 cases with intact MMR immunoexpression, the second group comprised 25 cases with at least one MMR protein being deficient. For further verification molecular genetic MSI testing, along with BRAF gene analysis and MLH1 promoter methylation status to discriminate Lynch syndrome from sporadic cases, were performed. Germline analysis of MMR genes proved the diagnosis of Lynch syndrome in 5 cases of the second group. Semi PREDICT score sensitivity for MMR-deficiency prediction (and indirectly for Lynch syndrome detection) was 84 %, specificity 48 %. Sensitivity of MSI testing was 87 %, but only 50 % in Lynch syndrome subset of cases, specificity was 100 %. The results show major role of MMR immunohistochemistry in the diagnostics of MSI-H cancers, which is the cornerstone of Lynch syndrome screening.
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Effect of colorectal cancer screening programs on lethality and incidence from this disease in the Czech Republic modeled by an APC approach
Čady, Ondřej ; Hulíková Tesárková, Klára (advisor) ; Kurtinová, Olga (referee)
This work will first introduce the problems related to the colorectal cancer - its epidemiology and screening possibilities. Next the main topic is addressed - i.e. to ascertain the influence of national screening programmes for colorectal cancer on really observed data of lethality and incidence of this disease. Group of so-called APC models was selected as a useful tool for this purpose. Applying these methods on data of The National Oncological Registry of the Czech Republic for the period between 1980 till 2009 this work aims to prove expected reducing effect of area-wide screening programme on incidence and lethality related to colorectal cancer. Using the AP model and data of previous period before the screening introduction (i.e. 1980-1999) the values of incidence and lethality were predicted for the period in question (i.e. 2000-2009). Mere comparison of this predicted values with really observed data showed that real lethality and incidence was significantly lower in both sexes as compared to the model without the screening intervention. Difference between predicted and real data corroborates positive influence of colorectal cancer screening.
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Determination of tumor mRNA in colorectal cancer as screening and forecasting methods
Rupert, Karel ; Holubec, Luboš (advisor) ; Hoch, Jiří (referee) ; Pešková, Marie (referee) ; Dostalík, Jan (referee)
The level of MMP-7, TIMP-1 and MMP-2 mRNA expression was significantly higher in the tumour tissue of colorectal carcinoma than in normal colorectal tissue. It could be possible to inhibit matrix metalloproteinases activity using appropriate antibodies, which could have therapeutic effect on tumour tissue and its vicinity. Some of the preparations are being tested (Bay 12-9566 /Bayer/, BB94 /British Biotechnology/). We have not proved correlation between expression of these genes and disease stage and diagnosis. We have succeeded to prove that if the surgical principles for colon resection performed due to colorectal carcinoma are observed, the resection line does not show any signs of the presence of tumour cells - mRNA for CEA is not present. The level of mRNA for TIMP-1 is present in the resection line at lower levels than in tumour tissue, and this is due to the role that TIMP- 1 plays in the colon. Its level increases not only in all tumour diseases, but also in inflammatory diseases of the colon. The question whether the expression of mRNA for TIMP-1 is also increased outside the resection line and therefore it is a reaction of the colon as an organ will be subject to further research, as will be a potential comparison with samples of colon unaffected by tumour or inflammation. Although the...
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Assessment of Biological Activity of Colorectal Carcinoma using RT REAL-TIME PCR
Pešta, Martin ; Topolčan, Ondřej (advisor) ; Pešek, Miloš (referee) ; Pecen, Ladislav (referee)
The author in his doctoral thesis, proposed primers and conditions optimized design Quantitative PCR for determining the gene expression of MMP-7, TIMP-1, MMP-2 and TIMP- second Revealed the presence of gene expression of GAPDH TIMP-1 and TIMP-2 in cancer line HT-29 SW480 and SW620. Noted the high level expression of MMP-7 in line HT-29th Expression of the 2-3 orders of magnitude higher than the lines SW480 and SW620. MRNA expression of MMP-2 in line HT-29 noticed. MRNA expression of MMP-2 by the detected lines SW480 and SW620. He found that determining absolute and relative expression in tumor lines is ekvivalentní. significantly higher mRNA expression of MMP-7, TIMP-1, MMP-2 and TIMP-2 in tumor tissue compared to normal tissue. It can be used in therapy. Noticed the presence of correlation of gene expression MMP-7, TIMP-1, MMP-2 and TIMP-2 with survival and DFI. He showed that a higher stage cancer correlated with a higher median momery MMP-2/TIMP-2. 7, Noticed the difference in gene expression between TS, TP and DPD in control and tumor tissue. Scored marginally significant increase in TS expression in colon tumors compared to tumors rectosigmoid and rectum. This finding can be used in treatment decisions. scored marginally significant correlation between the expression of TS and DPD. This finding can be...
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Rakovina tlustého střeva: prevence a příčiny ve vztahu k výživě člověka
Kolatková, Zuzana
Abstract This thesis is focused on colon cancer in relation to nutrition. The thesis contains information about the cause of developing cancer of the colon, risk factors and preventive dietary measures that have demonstrable link with this disease. It also includes information on the incidence of colorectal cancer (colon cancer) in the world, Europe and the Czech Republic. Ten countries from Europe, Asia and Africa are selected for the study. The rate of occurrence of this type of cancer is compared with aspects of lifestyle such as smoking, alcohol consumption, consumption of red meat obesity, physical activity, consumption of fruits, consumption of vegetables and consumption of fish.
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Use of molecular-genetic methods for research of colorectal carcinoma
Janáková, Tereza ; Škutková, Helena (referee) ; Provazník, Ivo (advisor)
The aim of this bachelor work is to carry out statistical analysis of mutations in KRAS, BRAF and PIK3CA genes. Introductory part is focused on colorectal carcinoma in general. In following part of the work, we discuss genetics of tumors, description of KRAS, BRAF and PIK3CA genes, molecular-genetic analytical methods, widely used in genetics, especially PCR. Further detection of mutations is described. In the next part of the work, we propose a method for detection of mutations in KRAS, BRAF and PIK3CA genes, which consist in using PCR and commercial kits. The following chapter "Results of Analysis of mutations" contains detailed grafical presentation of mutations. Frequencies of mutations were compared with published data and with data from laboratories in Pilsen and Prague. In the end of the bachalor work, there is summary of results and their possible benefit.
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Primary and Secondary Prevention of Colorectal Carcinoma by People over 50
HORNÍKOVÁ, Kateřina
As the title reveals, the thesis deals with primary and secondary prevention of colorectal carcinoma among people over 50 years of age. Colorectal carcinoma, i.e. tumour disease of the colon or rectum, is a serious disease with increasing incidence. The Czech Republic has one of the highest incidence rates of this disease and is at the forefront of global statistics. Every year, about 8000 people are diagnosed with colorectal carcinoma in our country and about 4000 patients die of this disease every year. Almost four people out of ten have vicarious experience with colorectal carcinoma, claiming that someone in their immediate vicinity has developed this disease. Early detection of the disease is thus of crucial importance. Prevention and diagnostics play a major role because tumours detected at an early stage can be treated well. It is reported that lifestyle, the right regimen, plenty of physical activity, wholesome food with an appropriate proportion of fibre and vitamins have a 60 to 80 % impact on the development of carcinoma. The disease poses a threat mainly to people over fifty years of age and people with genetic predispositions. The thesis is divided into a theoretical and practical part. The theoretical part consists of several chapters. First of all, I will be dealing with the basic anatomy and physiology of the colon and rectum. Then I will be dealing with the colorectal carcinoma itself, its development, symptoms, incidence or epidemiological aspects of the disease in the Czech Republic. I will be dealing with the risk factors of colorectal carcinoma that include age, lifestyle, as well as hereditary predispositions. A large part of the thesis is dedicated to colorectal carcinoma prevention. I will be focusing on primary and secondary prevention, including the faecal occult blood test and colonoscopy. Finally, I will touch on diagnostics and treatment of colorectal carcinoma. The practical part makes use of the research data obtained through a quantitative interrogation method, a questionnaire. The questionnaire was anonymous and included 32 questions. The first group of the questions was focused on basic information about the respondents. The rest of the questions concerned respondents´ awareness of colorectal carcinoma, its risk factors and potential prevention. I explored the respondents´ attitudes to lifestyle, their concern for tumour diseases in general, as well as whether they regularly see their physician. A substantial part of the questionnaire was devoted to questions regarding the occult blood test and colorectal screening. The questionnaire was intended for people over 50 years of age. The purpose of the thesis was to map awareness of the risk factors of colorectal carcinoma, look into awareness of the options of secondary prevention of colorectal carcinoma and whether people attend regular screenings. I examined the importance of giving media publicity to the disease and thus related interest in this issue. I wished to know whether there is a gender difference in the interest in undergoing colorectal screening. Four hypotheses were established in the research. Hypothesis 1: People over the age of 50 are informed about the risk factors of colorectal carcinoma. This hypothesis was confirmed. Hypothesis 2: People over the age of 50 know the options of secondary prevention of colorectal carcinoma. This hypothesis was only partially confirmed. Hypothesis 3: The number of colorectal screenings undergone by women over the age of 50 is statistically more significant than that of man over 50 years of age. This hypothesis was not confirmed for the occult blood test. However, men underwent colonoscopy more often. Hypothesis 4: The interest in undergoing colorectal screening increases with the level of education attained. The actual proportion of those who underwent an occult blood test or colonoscopy does not differ depending on education, and therefore hypothesis number 4 was not confirmed.
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