Protein-altering germline mutations implicate novel genes related to lung cancer development
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15120%2F20%3A73602737" target="_blank" >RIV/61989592:15120/20:73602737 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11110/20:10413827
Result on the web
<a href="https://www.nature.com/articles/s41467-020-15905-6" target="_blank" >https://www.nature.com/articles/s41467-020-15905-6</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41467-020-15905-6" target="_blank" >10.1038/s41467-020-15905-6</a>
Alternative languages
Result language
angličtina
Original language name
Protein-altering germline mutations implicate novel genes related to lung cancer development
Original language description
Few germline mutations are known to affect lung cancer risk. We performed analyses of rare variants from 39,146 individuals of European ancestry and investigated gene expression levels in 7,773 samples. We find a large-effect association with an ATM L2307F (rs56009889) mutation in adenocarcinoma for discovery (adjusted Odds Ratio=8.82, P=1.18x10(-15)) and replication (adjusted OR=2.93, P=2.22x10(-3)) that is more pronounced in females (adjusted OR=6.81 and 3.19 and for discovery and replication). We observe an excess loss of heterozygosity in lung tumors among ATM L2307F allele carriers. L2307F is more frequent (4%) among Ashkenazi Jewish populations. We also observe an association in discovery (adjusted OR=2.61, P=7.98x10(-22)) and replication datasets (adjusted OR=1.55, P=0.06) with a loss-of-function mutation, Q4X (rs150665432) of an uncharacterized gene, KIAA0930. Our findings implicate germline genetic variants in ATM with lung cancer susceptibility and suggest KIAA0930 as a novel candidate gene for lung cancer risk. In lung cancer, relatively few germline mutations are known to impact risk. Here the authors looked at rare variants in 39,146 individuals and find novel germline mutations associated with risk, as well as implicating ATM and a new candidate gene for lung cancer risk.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30302 - Epidemiology
Result continuities
Project
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Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2020
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature Communications
ISSN
2041-1723
e-ISSN
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Volume of the periodical
11
Issue of the periodical within the volume
1
Country of publishing house
GB - UNITED KINGDOM
Number of pages
14
Pages from-to
2220
UT code for WoS article
000558695400001
EID of the result in the Scopus database
2-s2.0-85084474621