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

Result code in 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>

Alternative codes found

RIV/00216208:11110/17:10362030

Result on the web

<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>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

10608 - Biochemistry and molecular biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

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

Publication year

2017

Confidentiality

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

Name of the periodical

OncoTarget

ISSN

1949-2553

e-ISSN

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Volume of the periodical

8

Issue of the periodical within the volume

7

Country of publishing house

US - UNITED STATES

Number of pages

9

Pages from-to

11739-11747

UT code for WoS article

000394187400089

EID of the result in the Scopus database

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