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Short article : Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy

Catalano, Calogerina ; Da Silva Filho, Miguel I. LU ; Jiraskova, Katerina ; Vymetalkova, Veronika ; Levy, Miroslav ; Liska, Vaclav ; Vycital, Ondrej ; Naccarati, Alessio ; Vodickova, Ludmila and Hemminki, Kari LU , et al. (2018) In European Journal of Gastroenterology and Hepatology 30(8). p.838-842
Abstract

Background NLRC5 is an interferon γ-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... (More)

Background NLRC5 is an interferon γ-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 (OS all and OS pM0) and event-free survival (EFS pM0) under a recessive model (OS all P=0.003, OS pM0 P=0.005, EFS pM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OS all P=0.03 and OS pM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OS all, OS pM0 and EFS pM0, according to the dosage of the minor allele T (OS all P=0.0004, OS pM0 P=0.0001, EFS pM0 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.

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publication status
published
subject
keywords
5-fluorouracil, colorectal cancer, NLRC5, survival analysis
in
European Journal of Gastroenterology and Hepatology
volume
30
issue
8
pages
5 pages
publisher
Lippincott Williams & Wilkins
external identifiers
  • scopus:85050020704
  • pmid:29762254
ISSN
0954-691X
DOI
10.1097/MEG.0000000000001154
language
English
LU publication?
yes
id
561c6817-c639-44da-bb2d-599288fab658
date added to LUP
2018-07-31 14:15:54
date last changed
2020-01-13 00:51:24
@article{561c6817-c639-44da-bb2d-599288fab658,
  abstract     = {<p>Background NLRC5 is an interferon γ-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 (OS all and OS pM0) and event-free survival (EFS pM0) under a recessive model (OS all P=0.003, OS pM0 P=0.005, EFS pM0 P=0.01, respectively). OS was also decreased for all patients and for pM0 patients who carried at least one minor allele of rs289747 (OS all P=0.03 and OS pM0 P=0.003, respectively). Among CRC patients, who underwent a 5-FU-based adjuvant regimen, rs12445252 was associated with OS all, OS pM0 and EFS pM0, according to the dosage of the minor allele T (OS all P=0.0004, OS pM0 P=0.0001, EFS pM0 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.</p>},
  author       = {Catalano, Calogerina and Da Silva Filho, Miguel I. and Jiraskova, Katerina and Vymetalkova, Veronika and Levy, Miroslav and Liska, Vaclav and Vycital, Ondrej and Naccarati, Alessio and Vodickova, Ludmila and Hemminki, Kari and Vodicka, Pavel and Weber, Alexander N.R. and Försti, Asta},
  issn         = {0954-691X},
  language     = {eng},
  month        = {08},
  number       = {8},
  pages        = {838--842},
  publisher    = {Lippincott Williams & Wilkins},
  series       = {European Journal of Gastroenterology and Hepatology},
  title        = {Short article : Influence of regulatory NLRC5 variants on colorectal cancer survival and 5-fluorouracil-based chemotherapy},
  url          = {http://dx.doi.org/10.1097/MEG.0000000000001154},
  doi          = {10.1097/MEG.0000000000001154},
  volume       = {30},
  year         = {2018},
}