11. 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: 380; Prenosov: 103
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12. Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesotheliomaKatja Goričar, Viljem Kovač, Vita Dolžan, 2014, izvirni znanstveni članek Povzetek: Introduction. A combination of pemetrexed and cisplatin has been shown to improve the outcome in patients with malignant pleural mesothelioma (MPM), however, there is a great heterogeneity in treatment response among patients. The aim of our study was to evaluate the influence of polymorphisms in folate pathway and transporter genes on pemetrexed treatment outcome in Slovenian patients with MPM. Methods. MPM patients treated with pemetrexed in the course of a prospective randomized clinical trial were genotyped for nineteen polymorphisms in five genes of folate pathway and six transporter genes. Logistic regression was used to assess the influence of polymorphisms on treatment efficacy and toxicity, while Cox regression was used to determine their influence on progression-free and overall survival. Results. Patients with at least one polymorphic MTHFD 1 rs2236225 allele had a significantly lower response rate (p = 0.005: odds ratio [OR] = 0.12; 95% confidence interval [CI] = 0.03-0.54) and shorter progression-free survival (p = 0.032: hazard ratio [HR) = 3.10: 95% CI = 1.10-8.74) than non-carriers. Polymorphisms in transporter genes did not influence survival; however, several were associated with toxicity. Liver toxicity was significantly lower in carriers of polymorphic ABCC2 rs2273697 (p = 0.028: OR = 0.23; 95% CI = 0.06-0.85). SLC01Bl rs4149056 (p = 0.028: OR = 0.23: 95% CI = 0.06-0.85) and rsll045879 (p = 0.014: OR = 0.18; 95% CI = 0.05-0.71) alleles compared to non-carriers, as well as in patients with SLC01Bl GCAC haplotype (p = 0.048; OR = 0.17; 95% CI = 0.03-0.98). Gastrointestinal toxicity was much more common in patients with polymorphic ABCC2 rs717620 allele (p = 0.004: OR = 10.67; 95% CI = 2.15-52.85) and ABCC2 CAG haplotype (p = 0.006: OR = 5.67: 95% CI = 1.64-19.66). Conclusions. MTHFD 1 polymorphism affected treatment response and survival. while polymorphisms in ABCC2 and SLC01Bl transporter genes influenced the risk for toxicity. These polymorphisms could serve as potential markers of pemetrexed treatment outcome in patients with MPM. Ključne besede: polymorphisms, folate pathway, mesothelioma Objavljeno v DiRROS: 16.04.2024; Ogledov: 302; Prenosov: 88
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13. Genetic polymorphisms in homologous recombination repair genes in healthy Slovenian population and their influence on DNA damageKatja Goričar, Nina Erčulj, Maja Zadel, Vita Dolžan, 2012, izvirni znanstveni članek Povzetek: Background. Homologous recombination (HR) repair is an important mechanism involved in repairing double-strand breaks in DNA and for maintaining genomic stability. Polymorphisms in genes coding for enzymes involved in this pathway may influence the ca pa city for DNA repair. The aim of this study was to select tag single nucleotide polymorphisms (SNPs) in specific genes involved in HR repair, to determine their allele frequencies in a healthy Slovenian population and their influence on DNA damage detected with comet assay. Materials and methods. In total 373 individuals were genotyped for nine tag SNPs in three genes: XRCC3 722C>T, XRCC3 -316A>G, RAD51 -98G>C, RAD51 -61G>T, RAD51 1 522T>G, NBS1 553G>C, NBS1 1197A>G, NBS1 37117C>T and NBS1 3474A>C using competitive allele-specific amplification (KASPar assay). Comet assay was performed in a subgroup of 26 individuals to determine the influence of selected SNPs on DNA damage. Results. We observed that age significantly affected genotype frequencies distribution of XRCC3 -316A>G (P = 0.039) in healthy male blood donors. XRCC3 722C>T (P = 0.005), RAD51 -61G>T IP = 0.023) and NBS1 553G>C (P = 0.008) had a statistically significant influence on DNA damage. Conclusions. XRCC3 722C> T, RAD51 -61 G> T and NBS 1 553G>C polymorphisms significantly affect the repa ir of damaged DNA and may be of clinical importance as they are common in Slovenian population. Objavljeno v DiRROS: 22.03.2024; Ogledov: 277; Prenosov: 95
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14. Dinamika dolžine telomerov v levkocitih po zdravljenju z obsevanjem pri raku dojkTanja Marinko, Sara Redenšek Trampuž, Ana Trstenjak, Vita Dolžan, Katarina Trebušak Podkrajšek, Katja Goričar, 2023, objavljeni znanstveni prispevek na konferenci Povzetek: Obsevanje je del standardnega zdravljenja bolnic z rakom dojk. Odgovor na zdravljenje z obsevanjem je pri vsakem posamezniku drugačen in je odvisen tudi od genetskih dejavnikov. Eden od novejših genetskih označevalcev odgovora na obsevanje je dolžina telomerov. Telomeri ščitijo kromosome pred krajšanjem in vzdržujejo genomsko stabilnost. Rezultati naše raziskave kažejo, da se dinamika spreminjanja dolžine telomerov takoj po zdravljenju z obsevanjem in v šestih mesecih po obsevanju pri bolnicah z neinvazivnim rakom dojk spreminja in bi lahko služila kot biološki označevalec odgovora na obsevanje. Molekularni mehanizmi, povezani s tem procesom, ostajajo zaenkrat večinoma neraziskani. Ključne besede: rak dojk, obsevanje, onkološko zdravljenje Objavljeno v DiRROS: 16.06.2023; Ogledov: 549; Prenosov: 275
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