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Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy
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SYSNO ASEP 0493571 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy Author(s) Catalano, C. (DE)
da Silva Filho, M.I. (DE)
Jirásková, Kateřina (UEM-P)
Vymetálková, Veronika (UEM-P) RID
Levý, M. (CZ)
Liška, V. (CZ)
Vyčítal, O. (CZ)
Naccarati, Alessio (UEM-P)
Vodičková, Ludmila (UEM-P) RID
Hemminki, K. (DE)
Vodička, Pavel (UEM-P) RID
Weber, A.N.R. (DE)
Försti, A. (DE)Source Title European Journal of Gastroenterology & Hepatology - ISSN 0954-691X
Roč. 30, č. 8 (2018), s. 838-742Number of pages 5 s. Language eng - English Country US - United States Keywords 5-fluorouracil ; colorectal cancer ; NLRC5 ; survival analysis Subject RIV EB - Genetics ; Molecular Biology OECD category Gastroenterology and hepatology Institutional support UEM-P - RVO:68378041 UT WOS 000438533500005 EID SCOPUS 85050020704 DOI 10.1097/MEG.0000000000001154 Annotation Background NLRC5 is an interferon gamma-inducible protein, which plays a role in immune surveillance with a potential influence on cancer survival.
Objective We aimed to evaluate the effect of potential regulatory variants in NLRC5 on overall survival and survival after 5-fluorouracil (5-FU)-based therapy of colorectal cancer (CRC) patients.
Patients and methods We carried out a case-only study in a Czech population of 589 cases, 232 received 5-FU-based therapy. Eleven variants within NLRC5 were selected using in-silico tools. Associations between polymorphisms and survival were assessed by Cox regression analysis adjusting for age at diagnosis, sex, and TNM stage. Survival curves were derived using the Kaplan-Meier method.
Results Two variants showed a significant association with survival. All patients and metastasis-free patients at the time of diagnosis (pM0) who were homozygous carriers of the minor allele of rs27194 had a decreased overall survival (OSall and OSpM0) and event-free survival (EFSpM0) under a recessive model (OSall P=0.003, OSpM0 P=0.005, EFSpM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OSall P=0.03 and OSpM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OSall, OSpM0 and EFSpM0, according to the dosage of the minor allele T (OSall P=0.0004, OSpM0 P=0.0001, EFSpM0 P=0.008, respectively).
Conclusion Our results showed that polymorphisms in NLRC5 may be used as prognostic markers of survival of CRC patients, as well as for survival in response to 5-FU treatment.Workplace Institute of Experimental Medicine Contact Lenka Koželská, lenka.kozelska@iem.cas.cz, Tel.: 241 062 218, 296 442 218 Year of Publishing 2019
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