1. Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseasesKatja Goričar, Viljem Kovač, Metoda Dodič-Fikfak, Vita Dolžan, Alenka Franko, 2020, izvirni znanstveni članek Povzetek: Background Asbestos exposure is associated with increased risk of several diseases, including malignant mesothelioma (MM). Cell surface glycoprotein mesothelin is overexpressed in MM and serum soluble mesothelin-related peptides (SMRP) were already proposed as a diagnostic or prognostic biomarker in MM. However, interindividual variability in serum SMRP levels limits the clinical usefulness. Our primary objective was to investigate the influence of MSLN rs1057147 on serum SMRP levels in asbestos-exposed subjects and patients with asbestos-related diseases as well as on survival in MM. Subjects and methods Among 782 asbestos-exposed subjects and patients with asbestos-related diseases, 154 had MM. Serum SMRP levels were determined using sandwich enzyme-linked immunosorbent assay. All subjects were genotyped for MSLN rs1057147 polymorphism using competitive allele-specific polymerase chain reaction. Nonparametric tests, logistic and Cox regression were used in statistical analysis to compare different subject groups. Results MM patients had significantly higher SMRP levels than all other subjects (p < 0.001). Compared to wild-type MSLN rs1057147 genotype, both heterozygotes and carriers of two polymorphic alleles had significantly higher SMRP levels among subjects without MM (p < 0.001), but not in MM patients (p = 0.424). If genotype information was included, specificity of SMRP increased from 88.5% to 92.7% for the optimal cutoff value. Overall survival was significantly shorter in MM patients carrying at least one polymorphic rs1057147 allele (HR = 1.72, 95% CI = 1.15-2.55, p = 0.008). Conclusions MSLN genetic variability affects serum SMRP levels and was associated with shorter survival of MM patients. Combination of genetic and serum factors could therefore serve as a better diagnostic or prognostic biomarker in MM patients.
Ključne besede: asbestos-related disease, malignant mesothelioma, mesothelin
Objavljeno v DiRROS: 16.07.2024; Ogledov: 13; Prenosov: 4
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2. The influence of genetic variability in IL1B and MIR146A on the risk of pleural plaques and malignant mesotheliomaPetra Piber, Neža Vavpetič, Katja Goričar, Vita Dolžan, Viljem Kovač, Alenka Franko, 2020, izvirni znanstveni članek Povzetek: Asbestos exposure is associated with the development of pleural plaques as well as malignant mesothelioma (MM). Asbestos fibres activate macrophages, leading to the release of inflammatory mediators including interleukin 1 beta (IL-1%). The expression of IL-1% may be influenced by genetic variability of IL1B gene or regulatory microRNAs (miRNAs). This study investigated the effect of polymorphisms in IL1B and MIR146A genes on the risk of developing pleural plaques and MM. Subjects and methods. In total, 394 patients with pleural plaques, 277 patients with MM, and 175 healthy control subjects were genotyped for IL1B and MIR146A polymorphisms. Logistic regression was used in statistical analysis. Results. We found no association between MIR146A and IL1B genotypes, and the risk of pleural plaques. MIR146A rs2910164 was significantly associated with a decreased risk of MM (OR = 0.31, 95% CI = 0.13%0.73, p = 0.008). Carriers of two polymorphic alleles had a lower risk of developing MM, even after adjustment for gender and age (OR = 0.34, 95% CI = 0.14%0.85, p = 0.020). Among patients with known asbestos exposure, carriers of at least one polymorphic IL1B rs1143623 allele also had a lower risk of MM in multivariable analysis (OR = 0.50, 95% CI = 0.28%0.92, p = 0.025). The interaction between IL1B rs1143623 and IL1B rs1071676 was significantly associated with an increased risk of MM (p = 0.050). Conclusions. Our findings suggest that genetic variability of inflammatory mediator IL-1% could contribute to the risk of developing MM, but not pleural plaques.
Ključne besede: asbestos, genetic variation, malignant mesothelioma, pleural plaques
Objavljeno v DiRROS: 16.07.2024; Ogledov: 10; Prenosov: 4
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3. Genetic polymorphisms in aquaporin 1 as risk factors for malignant mesothelioma and biomarkers of response to cisplatin treatmentBarbara Šenk, Katja Goričar, Viljem Kovač, Vita Dolžan, Alenka Franko, 2019, izvirni znanstveni članek Ključne besede: malignant mesothelioma, genetic polymorphism, cisplatin, biomarkers
Objavljeno v DiRROS: 05.07.2024; Ogledov: 67; Prenosov: 19
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5. Pharmacogenomic markers of glucorticoid responses in the initial phase of remission induction therapy in childhood acute lymphoblastic leukemiaVladimir Gasic, Branka Zukic, Biljana Stanković, Dragana Janić, Lidija Dokmanovic, Jelena Lazic, Nada Krstovski, Vita Dolžan, Janez Jazbec, Sonja Pavlovič, Nikola Kotur, 2018, izvirni znanstveni članek Ključne besede: pharmacogenomics, childhood ALL, glucocorticoids, glucocorticoid receptor gene, glutathione S-transferase genes, multidrug resistance 1 gene
Objavljeno v DiRROS: 11.06.2024; Ogledov: 110; Prenosov: 45
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6. The influence of genetic variability on the risk of developing malignant mesotheliomaAlenka Franko, Nika Kotnik, Katja Goričar, Viljem Kovač, Metoda Dodič-Fikfak, Vita Dolžan, 2018, izvirni znanstveni članek Ključne besede: malignant mesothelioma, genetic polymorphism, antioxidative enzymes, genetic variability
Objavljeno v DiRROS: 10.06.2024; Ogledov: 111; Prenosov: 39
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8. Association between SLC19A1 gene polymorphism and high dose methotrexate toxicity in childhood acute lymphoblastic leukaemia and non Hodgkin malignant lymphoma : introducing a haplotype based approachBarbara Faganel Kotnik, Janez Jazbec, Petra Bohanec Grabar, Christina Rodriguez-Antona, Vita Dolžan, 2017, izvirni znanstveni članek Ključne besede: acute lymphoblastic leukaemia, genetic polymorphism, haplotype, methotrexate
Objavljeno v DiRROS: 31.05.2024; Ogledov: 144; Prenosov: 118
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9. Antioxidant defence-related genetic variants are not associated with higher risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescenceAna Lina Vodušek, Katja Goričar, Barbara Gazić, Vita Dolžan, Janez Jazbec, 2016, izvirni znanstveni članek Povzetek: Background. Thyroid cancer is one of the most common secondary cancers after treatment of malignancy in childhood or adolescence. Thyroid gland is very sensitive to the carcinogenic effect of ionizing radiation, especially in children. Imbalance between pro- and anti-oxidant factors may play a role in thyroid carcinogenesis. Our study aimed to assess the relationship between genetic variability of antioxidant defence-related genes and the risk of secondary thyroid cancer after treatment of malignancy in childhood or adolescence. Patients and methods. In a retrospective study, we compared patients with childhood or adolescence primary malignancy between 1960 and 2006 that developed a secondary thyroid cancer (cases) with patients (controls), with the same primary malignancy but did not develop any secondary cancer. They were matched for age, gender, primary diagnosis and treatment (especially radiotherapy) of primary malignancy. They were all genotyped for SOD2 p.Ala16Val, CAT c.-262C>T, GPX1 p.Pro200Leu, GSTP1 p.Ile105Val, GSTP1 p.Ala114Val and GSTM1 and GSTT1 deletions. The influence of polymorphisms on occurrence of secondary cancer was examined by McNemar test and Cox proportional hazards model. Results. Between 1960 and 2006 a total of 2641 patients were diagnosed with primary malignancy before the age of 21 years in Slovenia. Among them 155 developed a secondary cancer, 28 of which were secondary thyroid cancers. No significant differences in the genotype frequency distribution were observed between cases and controls. Additionally we observed no significant influence of investigated polymorphisms on time to the development of secondary thyroid cancer. Conclusions. We observed no association of polymorphisms in antioxidant genes with the risk for secondary thyroid cancer after treatment of malignancy in childhood or adolescence. However, thyroid cancer is one of the most common secondary cancers in patients treated for malignancy in childhood or adolescence and the lifelong follow up of these patients is of utmost importance.
Ključne besede: secondary thyroid cancer, antioxidant genes, genetic polymorphism
Objavljeno v DiRROS: 09.05.2024; Ogledov: 181; Prenosov: 124
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10. Functional polymorphisms in antioxidant genes in Hurthle cell thyroid neoplasm - an association of GPX1 polymorphism and recurrent Hurthle cell thyroid carcinomaBlaž Krhin, Katja Goričar, Barbara Gazić, Vita Dolžan, Nikola Bešić, 2016, izvirni znanstveni članek Povzetek: Hurthle cells of the thyroid gland are very rich in mitochondria and oxidative enzymes. As a high level oxidative metabolism may lead to higher level of oxidative stress and can be associated with an increased risk for cancer, we investigated whether common functional polymorphisms in antioxidant genes (SOD2, CAT, GPX, GSTP1, GSTM1 and GSTT1) are associated with the development or clinical course of Hurthle cell thyroid carcinoma (HCTC). Methods. A retrospective study was performed in 139 patients treated by thyroid surgery for a Hurthle cell neoplasm. HCTC, Hurthle cell thyroid adenoma (HCTA) or Hurthle cell thyroid nodule (HCTN) were diagnosed by pathomorphology. DNA was extracted from cores of histologically confirmed normal tissue obtained from formalin-fixed paraffinembedded specimens and genotyped for investigated polymorphisms. Logistic regression was used to compare genotype distributions between patient groups. Results. HCTC, HCTA and HCTN were diagnosed in 53, 47 and 21 patients, respectively. Metastatic disease and recurrence of HCTC were diagnosed in 20 and 16 HCTC patients, respectively. Genotypes and allele frequencies of investigated polymorphisms did not deviate from Hardy-Weinberg equilibrium in patients with HCTC, HCTA and HCTN. Under the dominant genetic model we observed no differences in the genotype frequency distribution of the investigated polymorphisms when the HCTA and HCTN group was compared to the HCTC group for diagnosis of HCTC or for the presence of metastatic disease. However, GPX1 polymorphism was associated with the occurrence of recurrent disease (p = 0.040). Conclusions. GPX1 polymorphism may influence the risk for recurrent disease in HCTC.
Ključne besede: Hurthle cell thyroid carcinoma, Hurthle cell neoplasm, thyroid, oxidative stress
Objavljeno v DiRROS: 30.04.2024; Ogledov: 298; Prenosov: 72
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