Investigation of single and synergic effects of NLRC5 and PD-L1 variants on the risk of colorectal cancer

Autor:	Vaclav Liska, Ludmila Vodickova, Christoph Frank, Ondrej Vycital, Miroslav Levy, Calogerina Catalano, Pavel Vodicka, Veronika Vymetalkova, Miguel Inacio da Silva Filho, Alexander N.R. Weber, Katerina Jiraskova, Kari Hemminki, Alessio Naccarati, Asta Försti
Jazyk:	angličtina
Rok vydání:	2018
Předmět:	0301 basic medicine Oncology Male Heredity Colorectal cancer medicine.medical_treatment lcsh:Medicine Gene Expression Biochemistry B7-H1 Antigen Cohort Studies 0302 clinical medicine Cellular types Medicine and Health Sciences lcsh:Science Aged 80 and over Multidisciplinary biology Immune cells Intracellular Signaling Peptides and Proteins Middle Aged Nucleic acids Genetic Mapping medicine.anatomical_structure 030220 oncology & carcinogenesis White blood cells Female Colorectal Neoplasms Research Article Adult medicine.medical_specialty Cell biology Blood cells T cell Immunology T cells Single-nucleotide polymorphism Regulome Variant Genotypes Cytotoxic T cells Polymorphism Single Nucleotide Molecular Genetics 03 medical and health sciences Internal medicine PD-L1 microRNA DNA-binding proteins medicine Genetics Humans Gene Regulation Genetic Predisposition to Disease Non-coding RNA Molecular Biology Aged Colorectal Cancer lcsh:R Biology and Life Sciences Cancers and Neoplasms Proteins Immunotherapy medicine.disease Regulatory Proteins MicroRNAs 030104 developmental biology Animal cells Case-Control Studies biology.protein RNA lcsh:Q CD8 Transcription Factors
Zdroj:	PLoS ONE PLoS ONE, Vol 13, Iss 2, p e0192385 (2018)
ISSN:	1932-6203
Popis:	Constitutive activation of interferon signaling pathways has been reported in colorectal cancer (CRC), leading to a strong CD8+ T cell response through stimulation of NLRC5 expression. Primed CD8+ T cell expansion, however, may be negatively regulated by PD-L1 expression. Additionally, aberrant PD-L1 expression enables cancer cells to escape the immune attack. Our study aimed to select potential regulatory variants in the NLRC5 and PD-L1 genes by using several online in silico tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, microRNA and transcription factor binding site prediction tools and to investigate their influence on CRC risk in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Logistic regression analysis adjusted for age and gender reported a moderate association between rectal cancer risk and two NLRC5 SNPs, rs1684575 T>G (OR: 1.60, 95% CI: 1.13-2.27, recessive model) and rs3751710 (OR: 0.70, 95% CI: 0.51-0.96, dominant model). Given that a combination of genetic variants, rather than a single polymorphism, may explain better the genetic etiology of CRC, we studied the interplay between the variants within NLRC5, PD-L1 and the previously genotyped IFNGR1 and IFNGR2 variants, to evaluate their involvement in the risk of CRC development. Overall we obtained 18 pair-wise interactions within and between the NLRC5 ad PD-L1 genes and 6 more when IFNGR variants were added. Thirteen out of the 24 interactions were below the threshold for the FDR calculated and controlled at an arbitrary level q*T-NLRC5 rs289747 G>A (P
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::495f5c8b836804b886a960acf8a3d7e9 http://europepmc.org/articles/PMC5800657 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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