Coding variants in NOD-like receptors: An association study on risk and survival of colorectal cancer

Research output: Contribution to journalArticle

Abstract

Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.

Details

Authors
  • Stefanie Huhn
  • Miguel I. da Silva Filho
  • Tharmila Sanmuganantham
  • Tica Pichulik
  • Calogerina Catalano
  • Barbara Pardini
  • Alessio Naccarati
  • Veronika Polakova-Vymetálkova
  • Katerina Jiraskova
  • Ludmila Vodickova
  • Pavel Vodicka
  • Markus W. Löffler
  • Lioba Courth
  • Jan Wehkamp
  • Farhat V.N. Din
  • Maria Timofeeva
  • Susan M. Farrington
  • Lina Jansen
  • Jenny Chang-Claude
  • Hermann Brenner
  • Michael Hoffmeister
  • Malcolm G. Dunlop
  • Alexander N.R. Weber
Organisations
External organisations
  • German Cancer Research Centre
  • University Hospital Heidelberg
  • University of Tübingen
  • Institute of Experimental Medicine, Czech Academy of Science
  • Charles University in Prague
  • University Hospital of Tubingen
  • Center for Primary Health Care Research
  • Italian Institute for Genomic Medicine (IIGM)
  • University of Edinburgh
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cancer and Oncology
  • Medical Genetics
Original languageEnglish
Article numbere0199350
JournalPLoS ONE
Volume13
Issue number6
Publication statusPublished - 2018 Jun 1
Publication categoryResearch
Peer-reviewedYes