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Povezava med dovzetnostjo za razvoj raka želodca in variacijami v genih za popravilo DNA
ID Repa, Katarina (Author), ID Hudler, Petra (Mentor) More about this mentor... This link opens in a new window

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Abstract
Rak želodca je v svetovnem merilu tretji vodilni vzrok smrti zaradi raka. Kljub upadu incidence in smrtnosti v zadnjih desetletjih breme bolezni ostaja visoko in naj bi se v prihodnosti zaradi staranja populacije še zvišalo. Rak želodca je molekularno in fenotipsko izjemno heterogena bolezen, ki se pogosto diagnosticira šele v napredovalni fazi, ko je zdravljenje oteženo. Ena od možnih razlag za razlike v odzivu bolnikov na zdravljenje bi bili lahko polimorfizmi posameznega nukleotida (SNP) v genih za popravilo DNA. Geni, kot sta XRCC1 in ERCC1, sodelujejo v različnih mehanizmih popravila poškodb v DNA, ki jih med drugimi ustvarijo kemoterapevtska zdravila na osnovi platine, in so zato lahko povezani z učinkovitostjo zdravljenja. V magistrski nalogi smo na podlagi analize z bioinformacijskimi orodji izbrali kandidatne SNP-je rs1799782 in rs25487 v XRCC1 ter rs3212986 in rs11615 v ERCC1 in na vzorcih DNA bolnikov z rakom želodca iz slovenske populacije izvedli genotipizacijo s tehniko kompetitivne alelno specifične verižne reakcije s polimerazo. Nato smo s statističnimi analizami ovrednotili povezave med kandidatnimi SNP-ji in tveganjem za nastanek bolezni, kliničnimi kazalci in preživetjem bolnikov. Ugotovili smo, da je rs3212986 povezan z višjo dovzetnostjo za razvoj raka želodca. SNP-ji rs25487, rs3212986 in rs11615 so statistično značilno povezani z nekaterimi kliničnimi kazalci, kot so stopnja diferenciacije, histološki tip tumorja po Laurenu ter vaskularna invazija. Odkrili smo tudi, da so rs1799782, tip tumorja po Laurenu ter perinevralna invazija povezani s preživetjem bolnikov z rakom želodca. Razširitev naše študije bi lahko pomagala zdravnikom pri sprejemanju odločitev o zdravljenju te kompleksne bolezni.

Language:Slovenian
Keywords:rak želodca, geni za popravilo DNA, XRCC1, ERCC1, SNP, rs1799782, rs25487, rs3212986, rs11615
Work type:Master's thesis/paper
Typology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Year:2024
PID:20.500.12556/RUL-164115 This link opens in a new window
COBISS.SI-ID:212082179 This link opens in a new window
Publication date in RUL:17.10.2024
Views:83
Downloads:20
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Secondary language

Language:English
Title:Association of genetic variability in DNA repair genes with gastric cancer susceptibility
Abstract:
Gastric cancer is the third leading cause of cancer death worldwide. Despite declining incidence and mortality rates, the disease burden remains high and is expected to increase due to an aging population. Gastric cancer is molecularly and phenotypically very heterogeneous and is often diagnosed at an advanced stage when treatment options are limited. Differences in patient responses to treatment could be due to single nucleotide polymorphisms (SNPs) in DNA repair genes. Genes such as XRCC1 and ERCC1 play roles in various DNA repair mechanisms and could influence the efficacy of platinum-based chemotherapy. In this master's thesis, we selected candidate SNPs rs1799782 and rs25487 in XRCC1 and rs3212986 and rs11615 in ERCC1 for genotyping on DNA samples from Slovenian gastric cancer patients using competitive allele-specific polymerase chain reaction. Our statistical analyses evaluated the associations between these SNPs and the risk of disease onset, clinical-histopathological factors, and patient survival. We found that rs3212986 is associated with increased susceptibility to gastric cancer. The SNPs rs25487, rs3212986, and rs11615 were associated with specific clinical indicators, such as tumor grade, Lauren classification histological type, and vascular invasion. Additionally, rs1799782, tumor histological type, and perineural invasion were found to be associated with the survival of patients with gastric cancer. Broadening the scope of our study could assist clinicians in making more informed decisions regarding the treatment of patients with this complex disease.

Keywords:gastric cancer, DNA repair genes, XRCC1, ERCC1, SNP, rs1799782, rs25487, rs3212986, rs11615

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