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

Calogerina Catalano, Miguel I. Da Silva Filho, Katerina Jiraskova, Veronika Vymetalkova, Miroslav Levy, Vaclav Liska, Ondrej Vycital, Alessio Naccarati, Ludmila Vodickova, Kari Hemminki, Pavel Vodicka, Alexander N.R. Weber, Asta Försti

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish
Pages (from-to)838-842
Number of pages5
JournalEuropean Journal of Gastroenterology and Hepatology
Volume30
Issue number8
DOIs
Publication statusPublished - 2018 Aug 1

Subject classification (UKÄ)

  • Cancer and Oncology

Free keywords

  • 5-fluorouracil
  • colorectal cancer
  • NLRC5
  • survival analysis

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