Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11140%2F23%3A10464151" target="_blank" >RIV/00216208:11140/23:10464151 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f5P75gXa.R" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=f5P75gXa.R</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1093/jnci/djad043" target="_blank" >10.1093/jnci/djad043</a>
Alternative languages
Result language
angličtina
Original language name
Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions
Original language description
Background: The shared inherited genetic contribution to risk of different cancers is not fully known. In this study, we leverage results from twelve cancer genome-wide association studies (GWAS) to quantify pair-wise genome-wide genetic correlations across cancers and identify novel cancer susceptibility loci.Methods: We collected GWAS summary statistics for twelve solid cancers based on 376,759 cancer cases and 532,864 controls of European ancestry. The included cancer types were breast, colorectal, endometrial, esophageal, glioma, head and neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancers. We conducted cross-cancer GWAS and transcriptome-wide association studies (TWAS) to discover novel cancer susceptibility loci. Finally, we assessed the extent of variant-specific pleiotropy among cancers at known and newly identified cancer susceptibility loci.Results: We observed wide-spread but modest genome-wide genetic correlations across cancers. In cross-cancer GWAS and TWAS, we identified 15 novel cancer susceptibility loci. Additionally, we identified multiple variants at 77 distinct loci with strong evidence of being associated with at least two cancer types by testing for pleiotropy at known cancer susceptibility loci.Conclusions: Overall, these results suggest that some genetic risk variants are shared among cancers, though much of cancer heritability is cancer- and thus tissue-specific. The increase in statistical power associated with larger sample sizes in cross-disease analysis allows for the identification of novel susceptibility regions. Future studies incorporating data on multiple cancer types are likely to identify additional regions associated with the risk of multiple cancer types.
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
10600 - Biological sciences
Result continuities
Project
<a href="/en/project/NU21-07-00247" target="_blank" >NU21-07-00247: Concept of liquid biopsy in mapping of microRNA and oncogenic KRAS mutations for early diagnosis and risk assessment of pancreatic cancer.</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2023
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Journal of the National Cancer Institute
ISSN
0027-8874
e-ISSN
1460-2105
Volume of the periodical
115
Issue of the periodical within the volume
6
Country of publishing house
US - UNITED STATES
Number of pages
21
Pages from-to
712-732
UT code for WoS article
000975864100001
EID of the result in the Scopus database
2-s2.0-85163236294