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Epistatic effect of...
Epistatic effect of TLR3 and cGAS-STING-IKKε-TBK1-IFN signaling variants on colorectal cancer risk
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- Catalano, Calogerina (author)
- German Cancer Research Centre,Heidelberg University
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- da Silva Filho, Miguel Inacio (author)
- German Cancer Research Centre
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- Frank, Christoph (author)
- German Cancer Research Centre
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- Lu, Shun (author)
- University of Electronic Science and Technology of China
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- Jiraskova, Katerina (author)
- Charles University in Prague,Institute of Experimental Medicine, Czech Academy of Science
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- Vymetalkova, Veronika (author)
- Institute of Experimental Medicine, Czech Academy of Science,Charles University in Prague
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- Levy, Miroslav (author)
- Charles University in Prague
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- Liska, Vaclav (author)
- Charles University in Prague
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- Vycital, Ondrej (author)
- Charles University in Prague
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- Naccarati, Alessio (author)
- Institute of Experimental Medicine, Czech Academy of Science
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- Vodickova, Ludmila (author)
- Charles University in Prague,Institute of Experimental Medicine, Czech Academy of Science
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre
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- Vodicka, Pavel (author)
- Institute of Experimental Medicine, Czech Academy of Science,Charles University in Prague
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- Weber, Alexander N.R. (author)
- University of Tübingen
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups,German Cancer Research Centre,Hopp Children’s Cancer Center Heidelberg (KiTZ)
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(creator_code:org_t)
- 2019-12-23
- 2020
- English 12 s.
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In: Cancer Medicine. - : Wiley. - 2045-7634. ; 9:4, s. 1473-1484
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Abstract
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Keyword
- CRC
- interaction
- polygenic-risk-score
- risk
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Catalano, Caloge ...
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da Silva Filho, ...
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Frank, Christoph
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Lu, Shun
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Jiraskova, Kater ...
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Vymetalkova, Ver ...
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show more...
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Levy, Miroslav
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Liska, Vaclav
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Vycital, Ondrej
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Naccarati, Aless ...
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Vodickova, Ludmi ...
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Hemminki, Kari
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Vodicka, Pavel
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Weber, Alexander ...
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Försti, Asta
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Cancer Medicine
- By the university
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Lund University