| Popis: |
Polimorfizmi v bližini regulatornih delov gena XRCC6 so povezani z večjim tveganjem za pojav rakavih obolenj, kamor prištevamo tudi KLL. Večjo pojavnost rakavih obolenj so v azijski populaciji zaznali pri nosilcih alela G pri rs2267437 ter nosilcih alela C pri rs5751129. Namen magistrskega dela je bil ugotoviti, ali pojavnost določenih alelov/genotipov predstavlja napovedni dejavnik tveganja za slovensko populacijo bolnikov s KLL. Iz polne krvi bolnikov s KLL (N = 233) in kontrolne skupine (N = 121) smo izolirali DNA in z uporabo hidrolizirajočih sond TaqMan® določili genotipe za XRCC6 rs2267437 in XRCC6 rs5751129. V drugem sklopu smo preučevali vpliv genotipa ter kliničnih podatkov na hitrost napredovanja KLL, prikazanih kot čas, ki preteče od diagnoze do uvedbe terapije. V analizo preživetja po Kaplan – Meierju smo vključili 144 bolnikov s KLL. Rezultati magistrske naloge kažejo, da sta rs2267437 in rs5751129 v slovenski kohorti bolnikov in zdravih posameznikov v skladu s HW ravnotežjem. Med rizičnim alelom G (p = 0,6705) oz. rizičnima genotipoma CG in GG (p = 0,51) pri rs2267437 in rizičnim alelom C (p = 1,00) oz. rizičnima genotipoma CT in CC (p = 1,00) pri rs5751129 ter večjim tveganjem za pojav KLL v slovenski populaciji ni povezave, zato se le-ti ne morejo uporabiti kot napovedni dejavniki tveganja. Pojavnost polimorfizmov v slovenski populaciji se razlikuje od azijske populacije (p rs2267437 < 0,0001, p rs5751129 = 0,04), kjer obstaja povezava med genotipom in večjim tveganjem za pojav rakavih obolenj, ne razlikuje pa se od evropske (p rs2267437 = 0,67, p rs5751129 = 1,00), kjer tovrstne povezave niso dokazali. Ugotovili smo, da ni razlik v razporeditvi alelov (p rs2267437 = 0,48 p rs5751129 = 0,38) ali genotipov (p rs2267437 = 1,00, p rs5751129 = 0,14) med moškimi in ženskimi bolniki KLL. Nadalje smo ugotovili, da rizična genotipa CG in GG pri rs2267437 (p dominantni model = 0,58, p recesivni model = 0,51) in rizična genotipa CC in CT pri rs5751129 (p dominantni model = 0,34, p recesivni model = 0,44) ne vplivata na hitrejši potek bolezni pri bolnikih s KLL. Spol ne vpliva na hitrost napredovanja bolezni pri bolnikih s KLL (p = 0,41). Bolniki z neugodnimi citogenetskimi preureditvami del(11q22) in del(17q13) imajo hitrejši potek bolezni napram bolnikom z ugodnimi citogenetskimi preureditvami (p = 0,016). Bolniki v stadiju B ali C po Binetu imajo hitrejši potek bolezni napram tistim v stadiju A (p < 0,0001). Chronic lymphocytic leukemia (CLL) is the most common hematologic malignancy. Genetic polymorphisms in XRCC6 gene were associated with higher risk for certain types of cancer, including CLL. The G allele carriers in SNP rs2267437 and C allele carriers in SNP rs5751129 were found to be associated with a significant increase in risk of cancer in Asian population. The purpose of the master's thesis was to determine whether the occurrence of certain alleles/genotypes represents a predictive risk factor for Slovenian population of CLL patients. DNA was isolated from whole blood of CLL patients (N = 233) and control group (N = 121). Genotypes for XRCC6 rs2267437 and XRCC6 rs5751129 were determinated using TaqMan® hydrolysis probes. We also examined the influence of genotype and clinical data on the rate of progression of CLL, given as the time elapsed between diagnosis and initiation of treatment. 144 patients with CLL were included in the Kaplan - Meier survival analysis. The results show that rs2267437 and rs5751129 are HWE consistent in Slovenian cohort of patients and healthy individuals. There is no link between higher risk of CLL between risk allele G (p = 0.6705) or risk genotypes CG and GG (p = 0.51) in rs2267437 and risk allele C (p = 1.00) or risk genotypes CT and CC (p = 1.00) in rs5751129 in Slovenian population. Therefore they cannot be used as predictive risk factors. The prevalence of polymorphisms in Slovenian population differs from Asian population (p rs2267437 |
