Vloga polimorfizmov v genih matriksnih metaloproteinaz pri raku dojk

diplomsko delo visokošolskega strokovnega študijskega programa I. stopnje

Petra Berlak (Avtor), Uroš Potočnik (Mentor), Darja Arko (Komentor), Katja Repnik (Komentor)

Povzetek

Rak dojke je kompleksna, delno dedna bolezen, ki je v razvitem svetu še vedno najpogostejši rak pri ženskah. Medtem ko se je zunanjim dejavnikom, ki vplivajo na nastanek raka dojke mogoče do neke mere izogniti, pa se genetskim dejavnikom žal ni. Ker je genov, katerih okvara je kriva za nastanek bolezni veliko, je potrebno tudi veliko število študij in raziskav, saj je še veliko informacij neodkritih. Ključnega pomena je, da se izboljša dosedanja baza podatkov, saj to vodi k boljšemu razumevanju poteka same bolezni in posledično k bolj učinkovitemu zdravljenju, prilagojenemu samemu bolniku. Veliko vlogo pri samem poteku raka dojke imajo tudi polimorfizmi posameznega nukleotida (SNP), ki so variacija zaporedja DNK, ki se pojavi, ko se en sam nukleotid v genomu razlikuje med osebki iste biološke vrste. Pri preiskovanju teh polimorfizmov je zelo uspešna metoda asociacijske študije. V diplomski nalogi smo se osredotočili na polimorfizme SNP v genih matriksnih metaloproteinaz, ki so se izkazale kot pomembne pri raku dojk. Naš cilj je bil najti in razumeti vpliv polimorfizmov na nastanek same bolezni in njihovo vlogo v celotnem procesu zdravljenja. V študijo je bilo vključenih 77 slovenskih bolnic z rakom dojke in 123 zdravih posameznikov kot kontrolna skupina. Iz krvnih limfocitov bolnic z rakom dojke ter iz kontrol smo izolirali DNK na katerih smo genotipizirali izbrane polimorfizme na genih MMP1 (rs1799750 ter rs498186), MMP2 (rs243865), MMP3 (rs650108), MMP7 (rs11568818) ter MMP9 (rs3918242 ter rs17577). Genotipizacijo izbranih polimorfizmov smo izvedli z metodama PCR-RFLP ter qPCR-HRM. Nadalje smo izvedli statistično analizo podatkov s programom SPSS, kjer smo iskali povezavo med polimorfizmi in boleznijo s primerjavo frekvence genotipov in alelov bolnic in zdravih kontrolnih posameznikov. Ugotovili smo, da sta pri slovenskih bolnicah z rakom dojk povezana polimorfizma na genih MMP1 in MMP9. V primeru SNP-ja rs1799750 na genu MMP1 smo iz rezultatov ugotovili, da je delecija alela C pri tem polimorfizmu povezana z boleznijo, v primeru SNP-ja rs17577 na genu MMP9 pa smo ugotovili, da je bolezenski alel A.

Ključne besede

rak dojke;genotipizacija;asociacijska študija;diplomske naloge;

Podatki

Jezik:	Slovenski jezik
Leto izida:	2019
Tipologija:	2.11 - Diplomsko delo
Organizacija:	UM FKKT - Fakulteta za kemijo in kemijsko tehnologijo
Založnik:	[P. Berlak]
UDK:	618.19-006:591.151(043.2)
COBISS:	22674710
Št. ogledov:	773
Št. prenosov:	114
Ocena:	0 (0 glasov)
Metapodatki:

Ostali podatki

Sekundarni jezik:	Angleški jezik
Sekundarni naslov:	The role of polymorphisms in the genes coding for matrix metalloproteinases in breast cancer
Sekundarni povzetek:	Breast cancer is a complex, partially hereditary disease that is still the most common cancer in the developed world in women. While external factors that influence breast cancer can be avoided to some extent, genetic factors are unfortunately not avoidable. Since there are many genes whose defect is responsible for the onset of the disease, a large number of additional studies are needed because there is still a lot of undiscovered information. It is crucial to improve the existing database as this leads to a better understanding of the course of the disease itself and, consequently, to more effective patient-centered treatment. Single nucleotide polymorphisms (SNPs), which are a variation of the DNA sequence that occurs when a single nucleotide in the genome differs between individuals of the same species, also play a major role in the course of breast cancer. The association study method has proven to be very successful in investigating these polymorphisms. In the thesis, we focused on single nucleotide polymorphisms in matrix metalloproteinase genes, which have shown importance in breast cancer. Our goal was to find and understand the impact of these polymorphisms on the disease itself and their role in the overall treatment process. The study included 77 Slovenian breast cancer patients and 123 healthy individuals as a control group. DNA was isolated from the blood lymphocytes of patients with breast cancer and controls, on which we genotyped selected polymorphisms of MMP1 (rs1799750 and rs498186), MMP2 (rs243865), MMP3 (rs650108), MMP7 (rs11568818) and MMP9 (rs3918242 and rs17577). Genotyping of selected polymorphisms was performed using PCR-RFLP and qPCR-HRM methods. We further performed a statistical analysis of the data with the SPSS program, looking for a link between polymorphisms and disease by comparing the frequency of genotypes and alleles of patients and healthy control individuals. We found that polymorphisms of MMP1 and MMP9 genes are associated with breast cancer in Slovenian patients. In the case of the SNP rs1799750 on the MMP1 gene, we found from the results that deletion of the C allele in this polymorphism was associated with the disease, and in the case of the SNP rs17577 on the MMP9 gene, we found that the disease allele was allele A.
Sekundarne ključne besede:	breast cancer;SNP;genotyping;association study;
Vrsta dela (COBISS):	Diplomsko delo/naloga
Komentar na gradivo:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Strani:	IX, 45 str.
ID:	11215554