dissertation
Marija Rogar (Avtor), Radovan Komel (Mentor), Petra Hudler (Mentor)

Povzetek

INTRODUCTION. Gastric cancer represents the fifth most frequently diagnosed cancer in the world. Despite numerous research studies, mechanisms leading to disease are poorly known and unclear. At the molecular level, many changes are involved in the development of gastric cancer, including malfunction of chromosome segregation genes. These abnormalities can lead to chromosomal instability (CIN). Segregation gene function can be affected by the low penetrance errors which include polymorphisms. AIM. The aim of this study is to examine the effect of selected polymorphisms in specific segregation genes on gastric cancer development. HYPOTHESIS. The study focused on exploring genotypes of selected polymorphisms in specific mitotic segregation genes. Those that differ significantly between the subjects and the healthy control population, may be associated with higher risk for developing gastric cancer or with certain clinical and histopathological characteristics, and may have effect on the survival of gastric cancer patients. METHODS. 30 polymorphisms in genes BUB1B, CASC5, ESPL1, PTTG1, SMC1A, TPX2, TTK and ZWINT were included in the study. Subjects were compared with the control group. Polymorphisms were determined using quantitative real-time PCR (qPCR), restriction fragment length polymorphism (RFLP) and DNA sequencing. RESULTS. The association between polymorphisms rs2277559 (BUB1B), rs2241666 (ZWINT), rs11858113 (CASC5) and rs11855334 (CASC5) and increased risk of developing gastric cancer in male population was determined. As concerning rs11855334, statistically significant difference was also observed in the genotype distribution between the whole population of subjects and controls. The association between the genotypes of polymorphisms (in gene BUB1B) rs2277559, rs2290551, rs1801376, rs1047130, rs1565866, rs2277560 and Lauren classification was recognized. Genotypes of polymorphisms rs1801376 (BUB1B), rs11855334 (CASC5), rs2241666 (ZWINT), rs2910101 (PTTG1) and rs1047130 (BUB1B) are linked to different tumour differentiation grades. Survival analysis revealed association between the lymph node involvement and perineural invasion. Statistically higher frequencies of haplotypes G-A-G-T-G-G-A, G-G-A-G-A-A-G and A-G-G-T-A-G-A in gene BUB1B and of haplotypes A-A-A-C and C-C-G-T in gene ESPL1 were observed in gastric cancer patients, whereas haplotypes A-C-A-T and C-A-G-T in gene ESPL1 were significantly more frequent in the control group. Association with gastric cancer was not noted with other polymorphisms. CONCLUSIONS. The association between specific polymorphisms of selected chromosome segregation genes and gastric cancer was recognized. Findings could provide guidelines for further research and polymorphisms linked to gastric cancer could serve as potential diagnostic and prognostic biomarkers.

Ključne besede

gastric cancer;chromosomal instability;polymorphisms;segregation genes;

Podatki

Jezik: Angleški jezik
Leto izida:
Tipologija: 2.08 - Doktorska disertacija
Organizacija: UNG FPŠ - Fakulteta za podiplomski študij
Založnik: [M. Rogar]
UDK: 576
COBISS: 4454395 Povezava se bo odprla v novem oknu
Št. ogledov: 5242
Št. prenosov: 345
Ocena: 0 (0 glasov)
Metapodatki: JSON JSON-RDF JSON-LD TURTLE N-TRIPLES XML RDFA MICRODATA DC-XML DC-RDF RDF

Ostali podatki

Sekundarni jezik: Slovenski jezik
Sekundarni naslov: VPLIV POLIMORFIZMOV V SEGREGACIJSKIH GENIH NA RAZVOJ RAKA ŽELODCA
Sekundarni povzetek: IZHODIŠČE. Rak želodca je peta najpogosteje diagnosticirana oblika raka v svetovnem merilu. Kljub številnim raziskavam so mehanizmi, ki vodijo do nastanka bolezni, še vedno slabo poznani in nejasni. Na molekulski ravni so v razvoj raka na želodcu vpletene številne spremembe, med drugim tudi napake v delovanju segregacijskih genov. Omenjene nepravilnosti lahko vodijo v kromosomsko nestabilnost (CIN). Na spremembe v delovanju segregacijskih genov lahko vplivajo tudi napake z nizko penetranco, med katere uvrščamo polimorfizme. NAMEN. Z raziskavo smo želeli preveriti vpliv izbranih polimorfizmov v posameznih segregacijskih genih na razvoj raka želodca. HIPOTEZE. Želeli smo preveriti ali se genotipi izbranih polimorfizmov značilno razlikujejo med preiskovanci in kontrolami. Tisti, pri katerih ugotovimo značilno razliko, lahko vplivajo na višje tveganje za razvoj raka želodca in so povezani s patohistološkimi značilnostmi preiskovancev. Preveriti želimo, kakšen je njihov vpliv na preživetje bolnikov z rakom želodca. METODE. V študijo smo vključili 30 polimorfizmov v genih BUB1B, CASC5, ESPL1, PTTG1, SMC1A, TPX2, TTK in ZWINT. Primerjali smo preiskovance s kontrolno skupino. Za določanje polimorfizmov smo uporabili metode kvantitativni PCR v realnem času (qPCR), polimorfizem dolžin restrikcijskih fragmentov (RFLP) in določanje zaporedja nukleotidov (sekvenciranje DNA). REZULTATI. Ugotovili smo povezavo med polimorfizmi rs2277559 (BUB1B), rs2241666 (ZWINT), rs11858113 (CASC5) ter rs11855334 (CASC5) in višjim tveganjem za razvoj raka želodca pri moških. Pri rs11855334 se je značilna razlika v porazdelitvi genotipov pokazala tudi pri primerjavi celotne populacije preiskovancev in kontrol. Dokazali smo povezavo med genotipi polimorfizmov (v genu BUB1B) rs2277559, rs2290551, rs1801376, rs1047130, rs1565866, rs2277560 in Laurenovo klasifikacijo. Z različno stopnjo diferenciranosti tumorjev so povezani genotipi polimorfizmov rs1801376 (BUB1B), rs11855334 (CASC5), rs2241666 (ZWINT), rs2910101 (PTTG1) in rs1047130 (BUB1B). Analiza preživetja je pokazala, da je bilo preživetje preiskovancev povezano s prizadetostjo bezgavk in perinevralno invazijo. Bolniki z rakom želodca so imeli statistično značilno višje frekvence haplotipov G-A-G-T-G-G-A, G-G-A-G-A-A-G in A-G-G-T-A-G-A v genu BUB1B in haplotipov A-A-A-C in C-C-G-T v genu ESPL1. Haplotipa A-C-A-T in C-A-G-T v genu ESPL1 pa sta bila značilno bolj pogosta v kontrolni populaciji. Analize ostalih polimorfizmov niso pokazale povezave z rakom želodca. ZAKLJUČEK. Dokazali smo povezavo med posameznimi polimorfizmi izbranih mitoznih segregacijskih genov in rakom želodca. Ti polimorfizmi bi lahko služili kot smernice za nadaljnje raziskave, uporabni pa bi bili lahko tudi kot potencialni diagnostični in prognostični bio-označevalci.
Sekundarne ključne besede: rak želodca;kromosomska nestabilnost;polimorfizmi;segregacijski geni;disertacije;
URN: URN:SI:UNG
Vrsta dela (COBISS): Doktorsko delo/naloga
Komentar na gradivo: Univ. v Novi Gorici, Fak. za podiplomski študij
Strani: 144 str.
ID: 9158999