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Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer

Identifikátory výsledku

  • Kód výsledku v IS VaVaI

    <a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68378050%3A_____%2F17%3A00486602" target="_blank" >RIV/68378050:_____/17:00486602 - isvavai.cz</a>

  • Nalezeny alternativní kódy

    RIV/00216208:11110/17:10362030

  • Výsledek na webu

    <a href="http://dx.doi.org/10.18632/oncotarget.14340" target="_blank" >http://dx.doi.org/10.18632/oncotarget.14340</a>

  • DOI - Digital Object Identifier

    <a href="http://dx.doi.org/10.18632/oncotarget.14340" target="_blank" >10.18632/oncotarget.14340</a>

Alternativní jazyky

  • Jazyk výsledku

    angličtina

  • Název v původním jazyce

    Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer

  • Popis výsledku v původním jazyce

    Tibetans existed in high altitude for similar to 25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/ PHD2 and EPAS1/HIF-2a, both crucial components of hypoxia sensing, are the two bestestablished loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2: p.[D4E/C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay, however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/ HIF-2a have not yet been identified. Since HIF modulates the behavior of cancer cells, we hypothesized that these Tibetan selected genomic variants may modify cancer risk predisposition. Here, we ascertained the frequencies of EGLN1D4E/C127S and EGLN1C127S variants and ten EPAS1/HIF-2a variants in lung cancer patients and controls in Nepal, whose population consists of people with Indo-Aryan origin and Tibetan-related Mongoloid origin. We observed a significant association between the selected Tibetan EGLN1/PHD2 haplotype and lung cancer (p= 0.0012 for D4E, p= 0.0002 for C127S), corresponding to a two-fold increase in lung cancer risk. We also observed a two-fold or greater increased risk for two of the ten EPAS1/HIF-2a variants, although the association was not significant after correcting for multiple comparisons (p= 0.12). Although these data cannot address the role of these genetic variants on lung cancer initiation or progression, we conclude that some selected Tibetan variants are strongly associated with a modified risk of lung cancer.

  • Název v anglickém jazyce

    Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer

  • Popis výsledku anglicky

    Tibetans existed in high altitude for similar to 25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/ PHD2 and EPAS1/HIF-2a, both crucial components of hypoxia sensing, are the two bestestablished loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2: p.[D4E/C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay, however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/ HIF-2a have not yet been identified. Since HIF modulates the behavior of cancer cells, we hypothesized that these Tibetan selected genomic variants may modify cancer risk predisposition. Here, we ascertained the frequencies of EGLN1D4E/C127S and EGLN1C127S variants and ten EPAS1/HIF-2a variants in lung cancer patients and controls in Nepal, whose population consists of people with Indo-Aryan origin and Tibetan-related Mongoloid origin. We observed a significant association between the selected Tibetan EGLN1/PHD2 haplotype and lung cancer (p= 0.0012 for D4E, p= 0.0002 for C127S), corresponding to a two-fold increase in lung cancer risk. We also observed a two-fold or greater increased risk for two of the ten EPAS1/HIF-2a variants, although the association was not significant after correcting for multiple comparisons (p= 0.12). Although these data cannot address the role of these genetic variants on lung cancer initiation or progression, we conclude that some selected Tibetan variants are strongly associated with a modified risk of lung cancer.

Klasifikace

  • Druh

    J<sub>imp</sub> - Článek v periodiku v databázi Web of Science

  • CEP obor

  • OECD FORD obor

    10608 - Biochemistry and molecular biology

Návaznosti výsledku

  • Projekt

    Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

  • Návaznosti

    P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Ostatní

  • Rok uplatnění

    2017

  • Kód důvěrnosti údajů

    S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Údaje specifické pro druh výsledku

  • Název periodika

    OncoTarget

  • ISSN

    1949-2553

  • e-ISSN

  • Svazek periodika

    8

  • Číslo periodika v rámci svazku

    7

  • Stát vydavatele periodika

    US - Spojené státy americké

  • Počet stran výsledku

    9

  • Strana od-do

    11739-11747

  • Kód UT WoS článku

    000394187400089

  • EID výsledku v databázi Scopus