Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378041%3A_____%2F20%3A00539307" target="_blank" >RIV/68378041:_____/20:00539307 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11110/20:10418627 RIV/00216208:11140/20:10418627 RIV/00064190:_____/20:N0000015 RIV/00023001:_____/20:00079804 RIV/75010330:_____/20:00013325

Výsledek na webu

<a href="https://academic.oup.com/mutage/article-abstract/35/3/273/5699895?redirectedFrom=fulltext" target="_blank" >https://academic.oup.com/mutage/article-abstract/35/3/273/5699895?redirectedFrom=fulltext</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1093/mutage/gez050" target="_blank" >10.1093/mutage/gez050</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients

Popis výsledku v původním jazyce

The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e. whose variation influence the expression of many downstream genes. These SNPs were genotyped in a case-control study comprising 1098 cases and 1442 healthy controls and analysed in relation to CRC development risk and patient survival. Considering a strict correction for multiple tests, we did not observe any significant association between SNPs and CRC risk. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models [GA vs. GG, hazard ratio (HR) = 1.48, P= 0.002, AA vs. GG, HR = 1.70, P= 0.004 and GA + AA vs. GG, HR = 1.52, P= 0.0006]. Additionally, GA carriers of the same SNP displayed worse OS after receiving 5-FU based chemotherapy. The variant allele of rs3819720 polymorphism statistically significantly affected the expression of 36 downstream genes. Screening for eQTL polymorphisms in relevant genes such as ABC transporters that can regulate the expression of several other genes may help to identify the genetic background involved in the individual response to the treatment of CRC patients.

Název v anglickém jazyce

Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients

Popis výsledku anglicky

The chemotherapeutic efficacy in colorectal cancer (CRC) is limited due to the inter-individual variability in drug response and the development of tumour resistance. ATP-binding cassette (ABC) transporters are crucial in the development of resistance by the efflux of anticancer agents from cancer cells. In this study, we identified 14 single nucleotide polymorphisms (SNPs) in 11 ABC transporter genes acting as an expression of quantitative trait loci (eQTLs), i.e. whose variation influence the expression of many downstream genes. These SNPs were genotyped in a case-control study comprising 1098 cases and 1442 healthy controls and analysed in relation to CRC development risk and patient survival. Considering a strict correction for multiple tests, we did not observe any significant association between SNPs and CRC risk. The rs3819720 polymorphism in the ABCB3/TAP2 gene was statistically significantly associated with shorter overall survival (OS) in the codominant, and dominant models [GA vs. GG, hazard ratio (HR) = 1.48, P= 0.002, AA vs. GG, HR = 1.70, P= 0.004 and GA + AA vs. GG, HR = 1.52, P= 0.0006]. Additionally, GA carriers of the same SNP displayed worse OS after receiving 5-FU based chemotherapy. The variant allele of rs3819720 polymorphism statistically significantly affected the expression of 36 downstream genes. Screening for eQTL polymorphisms in relevant genes such as ABC transporters that can regulate the expression of several other genes may help to identify the genetic background involved in the individual response to the treatment of CRC patients.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

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

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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

Název periodika

Mutagenesis

ISSN

0267-8357

e-ISSN

—

Svazek periodika

35

Číslo periodika v rámci svazku

3

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

9

Strana od-do

273-281

Kód UT WoS článku

000593117600006

EID výsledku v databázi Scopus

2-s2.0-85088201245