Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Genome-Wide Analyses Characterize Shared Heritability Among Cancers and Identify Novel Cancer Susceptibility Regions

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10600 - Biological sciences

Projekt

<a href="/cs/project/NU21-07-00247" target="_blank" >NU21-07-00247: Využití konceptu tekuté biopsie pro charakterizaci mikroRNA a onkogenní KRAS mutace pro stanovení včasné diagnózy a zhodnocení rizika vzniku karcinomu pankreatu.</a><br>

Návaznosti

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

Rok uplatnění

2023

Kód důvěrnosti údajů

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

Název periodika

Journal of the National Cancer Institute

ISSN

0027-8874

e-ISSN

1460-2105

Svazek periodika

115

Číslo periodika v rámci svazku

6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

21

Strana od-do

712-732

Kód UT WoS článku

000975864100001

EID výsledku v databázi Scopus

2-s2.0-85163236294