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Epistatic effect of TLR3 and cGAS-STING-IKK epsilon-TBK1-IFN signaling variants on colorectal cancer risk

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收录情况： ◇ SCIE

作者：
Calogerina Catalano[1,2,*1] ; Miguel Inacio da Silva Filho[1] ; Christoph Frank[1] ; Shun Lu[3] ; Katerina Jiraskova[4,5] ; Veronika Vymetalkova[4,5,6] ; Miroslav Levy[7] ; Vaclav Liska[6,8] ; Ondrej Vycital[6,8] ; Alessio Naccarati[4,9] ; Ludmila Vodickova[4,5,6] ; Kari Hemminki[1,10] ; Pavel Vodicka[4,5,6] ; Alexander N. R. Weber[11] ; Asta Försti[1,10,12,13,*1] ;
机构： [1]Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2]Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany [3]Sichuan Cancer Center, School of Medicine, Sichuan Cancer Hospital & Institute, University of Electronic Science and Technology of China, Chengdu, China [4]Department of Molecular Biology of Cancer, Institute of Experimental Medicine, the Czech Academy of Sciences, Prague, Czech Republic [5]1st Medical Faculty, Institute of Biology and Medical Genetics, Charles University, Prague, Czech Republic [6]Faculty of Medicine in Pilsen, Biomedical Center, Charles University Prague, Pilsen, Czech Republic [7]First Medical Faculty, Department of Surgery, Charles University and Thomayer Hospital, Prague, Czech Republic [8]Department of Surgery, Teaching Hospital and Medical School of Charles University, Pilsen, Czech Republic [9]Molecular and Genetic Epidemiology, Italian Institute for Genomic Medicine (IIGM), Turin, Italy [10]Center for Primary Health Care Research, Clinical Research Center, Lund University, Malm., Sweden [11]Department of Immunology, Interfaculty Institute for Cell Biology, University of Tübingen, Baden-Württemberg, Tübingen, Germany [12]Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany [13]Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany
出处：
DOI： 10.1002/cam4.2804
ISSN：

关键词： CRC interaction polygenic-risk-score risk

摘要：
Objective The TLR3/cGAS-STING-IFN signaling has recently been reported to be disturbed in colorectal cancer due to deregulated expression of the genes involved. Our study aimed to investigate the influence of potential regulatory variants in these genes on the risk of sporadic colorectal cancer (CRC) in a Czech cohort of 1424 CRC patients and 1114 healthy controls. Methods The variants in the TLR3, CGAS, TMEM173, IKBKE, and TBK1 genes were selected using various online bioinformatic tools, such as UCSC browser, HaploReg, Regulome DB, Gtex Portal, SIFT, PolyPhen2, and miRNA prediction tools. Results Logistic regression analysis adjusted for age and sex detected a nominal association between CRC risk and three variants, CGAS rs72960018 (OR: 1.68, 95% CI: 1.11-2.53, P-value = .01), CGAS rs9352000 (OR: 2.02, 95% CI: 1.07-3.84, P-value = .03) and TMEM173 rs13153461 (OR: 1.53, 95% CI: 1.03-2.27, P-value = .03). Their cumulative effect revealed a threefold increased CRC risk in carriers of 5-6 risk alleles compared to those with 0-2 risk alleles. Epistatic interactions between these genes and the previously genotyped IFNAR1, IFNAR2, IFNA, IFNB, IFNK, IFNW, IRF3, and IRF7 genes, were computed to test their effect on CRC risk. Overall, we obtained nine pair-wise interactions within and between the CGAS, TMEM173, IKBKE, and TBK1 genes. Two of them remained statistically significant after Bonferroni correction. Additional 52 interactions were observed when IFN variants were added to the analysis. Conclusions Our data suggest that epistatic interactions and a high number of risk alleles may play an important role in CRC carcinogenesis, offering novel biological understanding for the CRC management.

基金：
The work was supported by Internal Grant Agency of the Ministry of Health of the Czech Republic under Grant AZV 15- 27580A and AZV 15-26535A; the Grant Agency of the Czech Republic under Grant 17-16857S; and the Center Of Clinical And Experimental Liver Surgery under Grant UNCE/MED/006. AW was supported by the University of Tübingen, the Federal State Baden-Württemberg Junior Professor Program.
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外文
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PubmedID：
中科院(CAS)分区：
出版当年[2020]版：
大类 | 3 区 医学
小类 | 3 区 肿瘤学
最新[2023]版：
大类 | 2 区 医学
小类 | 3 区 肿瘤学
JCR分区：
出版当年[2020]版：
Q2 ONCOLOGY
最新[2023]版：
Q2 ONCOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2]Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany [*1]Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, Baden-Württemberg, 69120, Germany.
通讯作者：
通讯机构： [1]Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany [2]Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany [10]Center for Primary Health Care Research, Clinical Research Center, Lund University, Malm., Sweden [12]Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany [13]Division of Pediatric Neurooncology, German Cancer Research Center (DKFZ), German Cancer Consortium (DKTK), Heidelberg, Germany [*1]Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, Heidelberg, Baden-Württemberg, 69120, Germany.
推荐引用方式(GB/T 7714)：
Calogerina Catalano,Miguel Inacio da Silva Filho,Christoph Frank,et al.Epistatic effect of TLR3 and cGAS-STING-IKK epsilon-TBK1-IFN signaling variants on colorectal cancer risk[J].CANCER MEDICINE.2020,9(4):1473-1484.doi:10.1002/cam4.2804.
APA：
Calogerina Catalano,Miguel Inacio da Silva Filho,Christoph Frank,Shun Lu,Katerina Jiraskova...&Asta Försti.(2020).Epistatic effect of TLR3 and cGAS-STING-IKK epsilon-TBK1-IFN signaling variants on colorectal cancer risk.CANCER MEDICINE,9,(4)
MLA：
Calogerina Catalano,et al."Epistatic effect of TLR3 and cGAS-STING-IKK epsilon-TBK1-IFN signaling variants on colorectal cancer risk".CANCER MEDICINE 9..4(2020):1473-1484

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