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.

Biomedical Centre Faculty of Medicine Pilsen Charles University Prague Pilsen Czech Republic

Center for Primary Health Care Research Clinical Research Center Lund University Malmö SE Sweden

Colon Cancer Genetics Group MRC Human Genetics Unit The University of Edinburgh Western General Hospital Edinburgh United Kingdom

Department of General Visceral and Transplant Surgery University Hospital Tübingen Tübingen Germany

Department of Internal Medicine 1 University Hospital Tübingen Tübingen Germany

Department of Molecular Genetic Epidemiology German Cancer Research Center Heidelberg Germany

Department of Multiple Myeloma Internal Medicine 5 Hematology Oncology and Rheumatology Heidelberg University Hospital Heidelberg Germany

Division of Cancer Epidemiology German Cancer Research Center Heidelberg Germany

Division of Clinical Epidemiology and Aging Research German Cancer Research Center Heidelberg Germany

Division of Preventive Oncology German Cancer Research Center Im Neuenheimer Feld 460 Heidelberg Germany

German Cancer Consortium Heidelberg Germany

Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Prague Czech Republic

Institute of Experimental Medicine Academy of Sciences of the Czech Republic Prague Czech Republic

Interfaculty Institute for Cell Biology Department of Immunology University of Tübingen Tübingen Germany

Italian Institute for Genomic Medicine Turin Italy

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