Immunosuppressive therapy in the posttransplant period and skin cancer.

Aims: To determine the incidence of malignancies in renal transplant recipients (RTRs) and to analyze the association between the risk of skin cancer and immunosuppressive regiments used in the posttransplant period.

Materials And Methods: A cohort study was performed on 797 RTRs. Standardized morbidity ratio (SMR) was calculated for the most common types of cancer developed in the posttransplant period and different types of immunosuppressive therapy used in the cohort.

Gastrointestinal comorbidities in patients with psoriasis in the Czech Republic: The results of 189 patients with psoriasis and 378 controls.

Aims: The aim of the study was to investigate gastrointestinal comorbidities, identify risk factors and detect the early stages of autoimmune gastrointestinal diseases, such as Crohn's disease, ulcerative colitis and coeliac disease in patients with psoriasis.

Methods: This was a hospital-based case-control study. Patients with chronic plaque psoriasis were included as cases.

Significantly higher incidence of skin cancer than other malignancies in patients after heart transplantation. A retrospective cohort study in the Czech Republic.

Aims: To perform the first study in Czech Republic on heart transplant recipients (HTRs), compare the risks for different types of cancer and provide comprehensive analysis of skin cancer and other types of cancer morbidity from which we would be able to derive an evidence-based skin cancer surveillance program.

Materials And Methods: A retrospective cohort study was performed to determine and compare standardized morbidity ratio (SMR) of different types of cancer developed after heart transplantation. We analysed data obtained from medical documentation of 603 HTRs transplanted between 1993 and 2010.

Structural chromosomal aberrations as potential risk markers in incident cancer patients.

Epidemiological prospective studies have shown that increased chromosomal aberrations (CAs) in peripheral blood lymphocytes may predict cancer risk. Here, we report CAs in newly diagnosed 101 colorectal, 87 lung and 158 breast cancer patients and corresponding healthy controls. Strong differences in distributions of aberrant cells (ACs), CAs, chromatid-type aberrations (CTAs) and chromosome-type aberrations (CSAs) were observed in lung and breast cancer patients as compared to healthy controls.

Metabolic gene variants associated with chromosomal aberrations in healthy humans.

Nonspecific chromosomal aberrations (CAs) are found in about 1% of lymphocytes drawn from healthy individuals. They include chromosome-type aberrations (CSAs), which are increased in exposure to ionizing radiation, and chromatid-type aberrations (CTAs) which in experimental systems are formed by DNA binding carcinogens and mutagens. The frequency of CAs is associated with the risk of cancer, but the causes of CAs in general population are unknown.

Risk factors for comorbidities in Czech psoriatic patients: results of a hospital-based case-control study.

Background: Psoriasis is now known to be associated with multiple other diseases/comorbidities - including the metabolic syndrome, atherosclerosis and gastrointestinal diseases which are all significantly higher in psoriasis patients. Research results however are highly variable and the conclusions are ambiguous. As no similar study has been performed to date in Czech psoriatic patients, this study aimed at identifying risk factors and early stages of selected diseases/comorbidities in the patients.

Chromosomal damage among medical staff occupationally exposed to volatile anesthetics, antineoplastic drugs, and formaldehyde.

Objectives: Structural chromosomal aberrations in blood lymphocytes represent a biomarker for cellular damage caused by genotoxic carcinogens and are an indicator of increased cancer risk. We evaluated the association between frequencies of total chromosomal aberrations, chromatid- and chromosome-type aberrations, and occupational exposures to volatile anesthetics, antineoplastic agents, and formaldehyde among 601 medical professionals.

Methods: Chromosomal damage among exposed individuals and unexposed controls was determined by conventional cytogenetic analysis.

Differences in nucleotide excision repair capacity between newly diagnosed colorectal cancer patients and healthy controls.

Alteration of DNA integrity is a potential cause of cancer and it is assumed that reduced DNA repair capacity and accumulation of DNA damage may represent intermediate markers in carcinogenesis. In this case-control study, DNA damage and nucleotide excision repair capacity (NER-DRC) were assessed in association with sporadic colorectal cancer (CRC). Both parameters were quantified by comet assay in blood cells of 70 untreated incident patients and 70 age-matched healthy controls.

DNA damage and nucleotide excision repair capacity in healthy individuals.

Interindividual differences in DNA repair capacity (DRC) represent an important source of variability in genome integrity and thus influence health risk. In the last decade, DRC measurement has attracted attention as a potential biomarker in cancer prediction. Aim of the present exploratory study was to characterize the variability in DNA damage and DRC on 100 healthy individuals and to identify biological, lifestyle, or genetic factors modulating these parameters.

Bile acid malabsorption in inflammatory bowel disease: assessment by serum markers.

Background: Bile acid malabsorption (BAM) is a common feature of Crohn's disease (CD). We aimed to determine whether BAM develops only in patients with a resected distal ileum or if it also occurs in patients who have not undergone surgery for CD.

Methods: The study included 347 patients with CD or ulcerative colitis (UC) and 119 healthy subjects (controls).

Superoxide dismutase and nicotinamide adenine dinucleotide phosphate: quinone oxidoreductase polymorphisms and pancreatic cancer risk.

Objectives: Pancreatic carcinoma etiology and molecular pathogenesis is weakly understood. According to the assumption that genetic variation in carcinogen metabolism further modifies the risk of exposure-related cancers, an association of functional polymorphisms in oxidative stress-modifying genes superoxide dismutase 2 (SOD2 [Ala16Val, rs4880]), SOD3 (Arg231Gly, rs1799895), nicotinamide adenine dinucleotide phosphate:quinone oxidoreductase (NQO1 [Pro187Ser, rs1800566], and NQO2 (Phe47Leu, rs1143684) with pancreatic cancer risk was studied.

Methods: Polymorphisms were studied by allelic discrimination.

DNA damage, DNA repair rates and mRNA expression levels of cell cycle genes (TP53, p21(CDKN1A), BCL2 and BAX) with respect to occupational exposure to styrene.

We studied the relationship between DNA damage, DNA repair rates and messenger RNA (mRNA) expression levels of cell cycle genes TP53, p21(CDKN1A), BCL2 and BAX in a group of 71 styrene-exposed workers and 51 control individuals. The exposure was assessed by measuring the concentration of styrene at workplace and in blood. Parameters of DNA damage [measured as single-strand breaks (SSBs) and endonuclease III-sensitive sites], γ-irradiation-specific DNA repair rates and mRNA levels of studied genes were analyzed in peripheral blood lymphocytes.

Association between exposure-relevant polymorphisms in CYP1B1, EPHX1, NQO1, GSTM1, GSTP1 and GSTT1 and risk of colorectal cancer in a Czech population.

Associations of functional single nucleotide polymorphisms in cytochrome P450 1B1, epoxide hydrolase 1, NAD(P)H:quinone oxidoreductase 1, glutathione S-transferase Pi-1 and deletions of glutathione S-transferases Mu-1 and θ-1 with colorectal cancer risk were investigated in a hospital-based case-control study on 495 matched pairs of Czech Caucasians. Polymorphisms were assessed by polymerase chain reaction restriction fragment length polymorphism-based methods, allele-specific multiplex and allelic discrimination by real-time polymerase chain reaction. Carriers of variant Ser allele in codon 453 of cytochrome P450 1B1 (rs1800440) were at a significantly lower risk of colorectal cancer compared to carriers of the wild-type allele (adjusted odds ratio, aOR=0.

Modulation of DNA repair capacity and mRNA expression levels of XRCC1, hOGG1 and XPC genes in styrene-exposed workers.

Decreased levels of single-strand breaks in DNA (SSBs), reflecting DNA damage, have previously been observed with increased styrene exposure in contrast to a dose-dependent increase in the base-excision repair capacity. To clarify further the above aspects, we have investigated the associations between SSBs, micronuclei, DNA repair capacity and mRNA expression in XRCC1, hOGG1 and XPC genes on 71 styrene-exposed and 51 control individuals. Styrene concentrations at workplace and in blood characterized occupational exposure.

Chromosomal damage in peripheral blood lymphocytes of newly diagnosed cancer patients and healthy controls.

Background: The majority of human cancers arise from cells unable to maintain genomic stability. Recent prospective studies indicated that enhanced chromosomal aberrations (CAs) frequencies are predictive of gastrointestinal and lung cancers. However, studies on incident cancer patients are lacking; thus, we investigated chromosomal damage in newly diagnosed cancer patients and healthy individuals.

Genotype and haplotype analysis of TP53 gene and the risk of pancreatic cancer: an association study in the Czech Republic.

Pancreatic carcinoma is the fourth leading cause of cancer-related deaths in the Czech Republic, with only a minimum of patients surviving 5 years. The aetiology and molecular pathogenesis are still weakly understood. TP53 has a fundamental role in cell cycle and apoptosis and is frequently mutated in solid tumours, including pancreatic cancer.

CYP2A13, ADH1B, and ADH1C gene polymorphisms and pancreatic cancer risk.

Objectives: Pancreatic carcinoma etiology and molecular pathogenesis are weakly understood. Based on the assumption that genetic variation in carcinogen metabolism further modifies the risk of exposure-related cancers, we studied the association of polymorphisms in the tobacco carcinogen-metabolizing gene CYP2A13 (Arg101Stop) and the alcohol-metabolizing genes ADH1B (Arg48His) and ADH1C (Ile350Val) with pancreatic cancer risk.

Methods: Polymorphisms were studied by allelic discrimination.

NBN 657del5 heterozygous mutations and colorectal cancer risk in the Czech Republic.

The most frequent Nijmegen breakage syndrome (NBS)-causing mutation is a 5-base pair deletion in gene coding for nibrin (NBN 657del5), which results in a non-fully functional protein product and is particularly frequent in Central and Eastern Europe. Recent studies have investigated whether NBN 657del5 carriage may predispose to an increased risk of different types of cancer. The Czech Republic has one of the highest incidences of colorectal cancer in the world as well as high incidence of NBS.

Genotype and haplotype analysis of cell cycle genes in sporadic colorectal cancer in the Czech Republic.

The Czech Republic has one of the highest incidences of colorectal cancer (CRC) in the world. To assess the role of genetic variants on the disease, we genotyped polymorphisms in the TP53 (rs17878362:A(1)>A(2), rs1042522:G>C, rs12947788:C>T, and rs17884306:G>A), CDKN1A (rs1801270:C>A and rs1059234:C>T), and CDKN2A (rs3731249:G>A, rs11515:C>G, and rs3088440:C>T) genes in 614 hospital-based CRC cases and 614 matched controls from the country. Despite the tendency toward differential distribution of variant allele frequencies for some polymorphisms, none was significantly associated with CRC risk.

Chromosomal aberrations in tire plant workers and interaction with polymorphisms of biotransformation and DNA repair genes.

We evaluated chromosomal aberrations in lymphocytes of 177 workers exposed to xenobiotics in a tire plant and in 172 controls, in relation to their genetic background. Nine polymorphisms in genes encoding biotransformation enzymes and nine polymorphisms in genes involved in main DNA repair pathways were investigated for possible modulation of chromosomal damage. Chromosomal aberration frequencies were the highest among exposed smokers and the lowest in non-smoking unexposed individuals (2.