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Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients
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SYSNO ASEP 0539307 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Expression quantitative trait loci in ABC transporters are associated with survival in 5-FU treated colorectal cancer patients Author(s) Vymetálková, Veronika (UEM-P) RID
Rosa, F. (IT)
Susová, S. (CZ)
Bendová, Petra (UEM-P)
Levý, M. (CZ)
Buchler, T. (CZ)
Král, J. (CZ)
Bártů, Linda (UEM-P)
Vodičková, Ludmila (UEM-P) RID
Hughes, D.J. (DE)
Souček, P. (CZ)
Naccarati, Alessio (UEM-P)
Kumar, R. (DE)
Vodička, Pavel (UEM-P) RID
Pardini, B. (IT)Source Title Mutagenesis. - : Oxford University Press - ISSN 0267-8357
Roč. 35, č. 3 (2020), s. 273-281Number of pages 9 s. Language eng - English Country GB - United Kingdom Keywords class-i antigen ; down-regulation ; gene-expression Subject RIV FR - Pharmacology ; Medidal Chemistry OECD category Pharmacology and pharmacy R&D Projects NV19-09-00237 GA MZd - Ministry of Health (MZ) GA17-16857S GA ČR - Czech Science Foundation (CSF) Method of publishing Limited access Institutional support UEM-P - RVO:68378041 UT WOS 000593117600006 EID SCOPUS 85088201245 DOI https://doi.org/10.1093/mutage/gez050 Annotation 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. Workplace Institute of Experimental Medicine Contact Arzuv Čaryjeva, arzuv.caryjeva@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2021 Electronic address https://academic.oup.com/mutage/article-abstract/35/3/273/5699895?redirectedFrom=fulltext
Number of the records: 1