Genetski dejavniki tveganja za ponovitev primarnega črevesnega raka

diplomsko delo univerzitetnega študijskega programa I. stopnje

Alja Čontala (Author), Uroš Potočnik (Mentor)

Abstract

Rak debelega črevesa in danke (RDČD) je maligno tumorsko obolenje z visoko pojavnostjo in umrljivostjo. V Sloveniji ima ob postavitvi diagnoze kar 60 % bolnikov že napredovano bolezen, pri skoraj tretjini le-teh pa pride do ponovitve bolezni. K razvoju bolezni pomembno vplivajo dedni polimorfizmi posameznega nukleotida (SNP) v genih povezanih z nastankom RDČD, kot tudi SNP – ji v genih, ki prispevajo k nastanku oddaljenih zasevkov oz. metastaz. V diplomskem delu smo ugotavljali vlogo izbranih SNP – jev v genih MMP7 (rs11568818) in MACC1 (rs1990172) pri razsoju v bezgavke ter ponovitvi RDČD. DNA smo izolirali iz tkivnih vzorcev črevesne sluznice, vpetih v parafin in izvedli gensko tipizacijo za izbrane polimorfizme s pomočjo tehnik HRM (analiza talilne krivulje visoke ločljivosti) in PCR – RFLP. Primerjali smo frekvence genotipov in alelov za izbrane polimorfizme pri bolnikih in zdravih posameznikih. Nato smo primerjali še alelne in genotipske frekvence med bolniki z RDČD glede na stadij po TNM klasifikaciji, ponovitev RDČD in nekatere druge klinične podatke. V primeru obeh polimorfizmov smo zaznali povečano frekvenco genotipa GG pri bolnikih v primerjavi z zdravimi kontrolami. Za SNP rs11568818 v genu MMP7 smo med bolniki z RDČD v primeru genotipa AA in alela A ugotovili signifikantno povezavo s povečanim tveganjem za širjenje in ponovitev bolezni (p = 0,03 in p = 0,009). Naša raziskava lahko skupaj z mnogimi drugimi pomembno vpliva na opredelitev SNP – jev za povečano tveganje za ponovitev RDČD in omogoči ustreznejšo prilagoditev zdravljenja za vsakega posameznika.

Keywords

rak debelega črevesa in danke;jetrne metastaze;ponovitev RDČD;genetski dejavniki tveganja;genotipizacija;FFPE tkiva;

Data

Language:	Slovenian
Year of publishing:	2014
Typology:	2.11 - Undergraduate Thesis
Organization:	UM FKKT - Faculty of Chemistry and Chemical Engineering
Publisher:	[A. Gabor]
UDC:	616.34/.36-006-033.2:575.22+577.21(043.2)
COBISS:	18214934
Views:	1360
Downloads:	215
Average score:	0 (0 votes)
Metadata:

Other data

Secondary language:	English
Secondary title:	GENETIC RISK FACTORS FOR RECURRENCE OF PRIMARY COLON CANCER
Secondary abstract:	Colorectal cancer (CRC) is a malignant tumour disease with high incidence and mortality. In Slovenia, at diagnosis at 60 % of patients advanced disease is developed. In nearly one third of cases relapse occurs. The development of the disease significantly affects hereditary SNPs in genes, associated with CRC as well as SNPs in genes that contribute to the occurrence of the distant metastases. In our research we determined the role of the selected SNPs in the genes MMP7 (rs11568818) and MACC1 (rs1990172) in the glow of the lymph nodes and CRC recurrence. DNA was isolated from FFPE tissue samples of the intestinal mucosa and performed genotyping of selected SNPs using the techniques of HRM (High Resolution Melting) and PCR - RFLP. We compared the genotypic and allelic frequencies of patients with those of healthy individuals. Then we compared the allelic and genotypic frequencies between the patients with CRC depending on the stage of the TNM classification, CRC recurrence and some other clinical parameters. In the case of both polymorphisms increased frequency of GG genotype in the group of patients compared with healthy controls was detected. For SNP rs11568818 in the case of AA genotype and allele A was a significant connection with increased risk of the spread and recurrence of the disease (p = 0,03 and p = 0,009). Our study, together with many others has got an important influence on the definition nucleotide polymorphisms an increased risk for recurrence of CRC and allows more appropriate treatment adjustments for each individual.
Secondary keywords:	colorectal cancer;liver metastases;colorectal cancer recurrence;genetics risk factors;genotyping;FFPE tissues;
URN:	URN:SI:UM:
Type (COBISS):	Bachelor thesis/paper
Thesis comment:	Univ. v Mariboru, Fak. za kemijo in kemijsko tehnologijo
Pages:	X, 79 str.
ID:	8730359