The mutagenic forces shaping the genomes of lung cancer in never smokers
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F25%3A10499301" target="_blank" >RIV/00064203:_____/25:10499301 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/25:10499301
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=460~xFjW8j" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=460~xFjW8j</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41586-025-09219-0" target="_blank" >10.1038/s41586-025-09219-0</a>
Alternative languages
Result language
angličtina
Original language name
The mutagenic forces shaping the genomes of lung cancer in never smokers
Original language description
Lung cancer in never smokers (LCINS) accounts for around 25% of all lung cancers(1,2) and has been associated with exposure to second-hand tobacco smoke and air pollution in observational studies(3-5). Here we use data from the Sherlock-Lung study to evaluate mutagenic exposures in LCINS by examining the cancer genomes of 871 treatment-naive individuals with lung cancer who had never smoked, from 28 geographical locations. KRAS mutations were 3.8 times more common in adenocarcinomas of never smokers from North America and Europe than in those from East Asia, whereas a higher prevalence of EGFR and TP53 mutations was observed in adenocarcinomas of never smokers from East Asia. Signature SBS40a, with unknown cause(6), contributed the largest proportion of single base substitutions in adenocarcinomas, and was enriched in cases with EGFR mutations. Signature SBS22a, which is associated with exposure to aristolochic acid(7,8), was observed almost exclusively in patients from Taiwan. Exposure to secondhand smoke was not associated with individual driver mutations or mutational signatures. By contrast, patients from regions with high levels of air pollution were more likely to have TP53 mutations and shorter telomeres. They also exhibited an increase in most types of mutations, including a 3.9-fold increase in signature SBS4, which has previously been linked with tobacco smoking(9), and a 76% increase in the clock-like(10) signature SBS5. A positive dose-response effect was observed with air-pollution levels, correlating with both a decrease in telomere length and an increase in somatic mutations, mainly attributed to signatures SBS4 and SBS5. Our results elucidate the diversity of mutational processes shaping the genomic landscape of lung cancer in never smokers.
Czech name
—
Czech description
—
Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
30304 - Public and environmental health
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Nature
ISSN
0028-0836
e-ISSN
1476-4687
Volume of the periodical
644
Issue of the periodical within the volume
8075
Country of publishing house
GB - UNITED KINGDOM
Number of pages
12
Pages from-to
133-144
UT code for WoS article
001521967400001
EID of the result in the Scopus database
2-s2.0-105009633828