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
—