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

Result code in 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>

Alternative codes found

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

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30104 - Pharmacology and pharmacy

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2020

Confidentiality

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

Name of the periodical

Mutagenesis

ISSN

0267-8357

e-ISSN

—

Volume of the periodical

35

Issue of the periodical within the volume

3

Country of publishing house

GB - UNITED KINGDOM

Number of pages

9

Pages from-to

273-281

UT code for WoS article

000593117600006

EID of the result in the Scopus database

2-s2.0-85088201245