Polymorphisms in microRNA binding sites of mucin genes as predictors of clinical outcome in colorectal cancer patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F17%3A00469319" target="_blank" >RIV/68378041:_____/17:00469319 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/17:10327401 RIV/00216208:11140/17:10327401 RIV/00064190:_____/17:N0000089

Výsledek na webu

<a href="http://dx.doi.org/10.1093/carcin/bgw114" target="_blank" >http://dx.doi.org/10.1093/carcin/bgw114</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/carcin/bgw114" target="_blank" >10.1093/carcin/bgw114</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Polymorphisms in microRNA binding sites of mucin genes as predictors of clinical outcome in colorectal cancer patients

Popis výsledku v původním jazyce

Polymorphisms in microRNA (miRNA) binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and susceptibility to common diseases. Mucins have been identified as markers of adverse prognosis. We hypothesized that genetic variations in miRNA binding sites located in mucin genes may modulate signaling response and the maintenance of genomic stability ultimately affecting cancer susceptibility, efficacy of chemotherapy and survival. In this study, we analyzed the association of single nucleotide polymorphisms in predicted miRNA target sites (miRSNPs) of mucin genes with colorectal cancer (CRC) risk and clinical outcome. Thirteen miRSNPs in 9 genes were assessed in 1111 cases and 1469 controls. No strongly significant associations were observed in the case-control study. Patients carrying the CC genotype of rs886403 in MUC21 displayed a shorter survival and higher recurrence risk when compared with TT carriers (overall survival (OS): hazard ratios (HR) 1.69, 95% confidence intervals (CI) 1.13-2.46, P = 0.01 and event-free survival (EFS): HR 1.99, 95% CI 1.38-2.84, P = 0.0002, respectively). The observed associations were more striking after stratification for tumor site (in patients with colon cancer, OS: HR 2.63, 95% CI 1.69-4.10, P < 0.0001 and EFS: HR 2.65, 95% CI 1.72-4.07, P < 0.0001). In contrast, rectal cancer cases carrying the CC genotype of rs4729655 in MUC17 displayed a longer survival (OS: HR 0.27, 95% CI 0.14-0.54, P = 0.0002) than those with the most common genotype. To our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to mucin genes and revealing their impact on CRC susceptibility or patients survival.

Název v anglickém jazyce

Polymorphisms in microRNA binding sites of mucin genes as predictors of clinical outcome in colorectal cancer patients

Popis výsledku anglicky

Polymorphisms in microRNA (miRNA) binding sites may affect miRNA/target gene interaction, resulting in differential mRNA/protein expression and susceptibility to common diseases. Mucins have been identified as markers of adverse prognosis. We hypothesized that genetic variations in miRNA binding sites located in mucin genes may modulate signaling response and the maintenance of genomic stability ultimately affecting cancer susceptibility, efficacy of chemotherapy and survival. In this study, we analyzed the association of single nucleotide polymorphisms in predicted miRNA target sites (miRSNPs) of mucin genes with colorectal cancer (CRC) risk and clinical outcome. Thirteen miRSNPs in 9 genes were assessed in 1111 cases and 1469 controls. No strongly significant associations were observed in the case-control study. Patients carrying the CC genotype of rs886403 in MUC21 displayed a shorter survival and higher recurrence risk when compared with TT carriers (overall survival (OS): hazard ratios (HR) 1.69, 95% confidence intervals (CI) 1.13-2.46, P = 0.01 and event-free survival (EFS): HR 1.99, 95% CI 1.38-2.84, P = 0.0002, respectively). The observed associations were more striking after stratification for tumor site (in patients with colon cancer, OS: HR 2.63, 95% CI 1.69-4.10, P < 0.0001 and EFS: HR 2.65, 95% CI 1.72-4.07, P < 0.0001). In contrast, rectal cancer cases carrying the CC genotype of rs4729655 in MUC17 displayed a longer survival (OS: HR 0.27, 95% CI 0.14-0.54, P = 0.0002) than those with the most common genotype. To our knowledge, this is the first study investigating miRSNPs potentially affecting miRNA binding to mucin genes and revealing their impact on CRC susceptibility or patients survival.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Carcinogenesis

ISSN

0143-3334

e-ISSN

—

Svazek periodika

38

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

12

Strana od-do

28-39

Kód UT WoS článku

000397050700005

EID výsledku v databázi Scopus

—