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@ARTICLE{Naderi:284938,
author = {E. Naderi and M. E. Aguado-Barrera and L. M. H. Schack and
L. Dorling and T. Rattay and L. Fachal and H. Summersgill
and L. Martínez-Calvo and C. Welsh and T. Dudding and Y.
Odding and A. Varela-Pazos and R. Jena and D. J. Thomson and
R. J. H. M. Steenbakkers and J. Dennis and R. Lobato-Busto
and J. Alsner and A. Ness and C. Nutting and A.
Gómez-Caamaño and J. G. Eriksen and S. J. Thomas and A. M.
Bates and A. J. Webb and A. Choudhury and B. S. Rosenstein
and B. Taboada-Valladares and C. Herskind and D. Azria and
D. P. Dearnaley and D. de Ruysscher and E. Sperk and E. Hall
and H. Stobart and J. Chang-Claude$^*$ and K. De Ruyck and
L. Veldeman and M. Altabas and M. C. De Santis and M.-P.
Farcy-Jacquet and M. R. Veldwijk and M. R. Sydes and M.
Parliament and N. Usmani and N. G. Burnet and P. Seibold$^*$
and R. P. Symonds and R. M. Elliott and R. Bultijnck and S.
Gutiérrez-Enríquez and M. Mollà and S. L. Gulliford and
S. Green and T. Rancati and V. Reyes and A. Carballo and P.
Peleteiro and P. Sosa-Fajardo and C. Parker and V. Fonteyne
and K. Johnson and M. Lambrecht and B. Vanneste and R.
Valdagni and A. Giraldo and M. Ramos and B. Diergaarde and
G. Liu and S. M. Leal and M. L. K. Chua and M. Pring and J.
Overgaard and L. M. Cascallar-Caneda and F. Duprez and C. J.
Talbot and G. C. Barnett and A. M. Dunning and A. Vega and
C. N. Andreassen and J. A. Langendijk and C. M. L. West and
B. Z. Alizadeh and S. L. Kerns},
collaboration = {O. t. b. o. t. R. Consortium},
title = {{L}arge-{S}cale {M}eta-{GWAS} {R}eveals {C}ommon {G}enetic
{F}actors {L}inked to {R}adiation-{I}nduced {A}cute
{T}oxicities across {C}ancers.},
journal = {JNCI cancer spectrum},
volume = {7},
number = {6},
issn = {2515-5091},
address = {Oxford},
publisher = {Oxford University Press},
reportid = {DKFZ-2023-02138},
pages = {pkad088},
year = {2023},
note = {2023 Oct 31;7(6):pkad088},
abstract = {This study was designed to identify common genetic
susceptibility and shared genetic variants associated with
acute radiation-induced toxicity (RIT) across four cancer
types (prostate, head and neck, breast, and lung).A GWAS
meta-analysis was performed using 19 cohorts including
12,042 patients. Acute standardized total average toxicity
(rSTATacute) was modelled using a generalized linear
regression model for additive effect of genetic variants
adjusted for demographic and clinical covariates. LD score
regression estimated shared SNP-based heritability of
rSTATacute in all patients and for each cancer type.Shared
SNP-based heritability of STATacute among all cancer types
was estimated at $10\%$ (se = 0.02), and was higher for
prostate $(17\%,$ se = 0.07), head and neck $(27\%,$ se =
0.09), and breast $(16\%,$ se = 0.09) cancers. We identified
130 suggestive associated SNPs with rSTATacute
(5.0x10-8<P-value<1.0x10-5) across 25 genomic regions.
rs142667902 showed the strongest association (effect allele
A; effect size -0.17; P-value=1.7x10-7), which is located
near DPPA4, encoding a protein involved in pluripotency in
stem cells, which are essential for repair of
radiation-induced tissue injury. Gene-set enrichment
analysis identified 'RNA splicing via endonucleolytic
cleavage and ligation' (P = 5.1 x10-6, Pcorrected =0.079) as
the top gene set associated with rSTATacute among all
patients. In-silico gene expression analysis showed the
genes associated with rSTATacute were statistically
significantly up-regulated in skin (not sun exposed
Pcorrected=0.004; sun exposed Pcorrected=0.026).There is
shared SNP-based heritability for acute RIT across and
within individual cancer sites. Future meta-GWAS among large
radiotherapy patient cohorts are worthwhile to identify the
common causal variants for acute radiotoxicity across cancer
types.},
keywords = {GWAS (Other) / Radiogenomics (Other) / SNP-based
heritability (Other) / acute radiation-induced toxicity
(Other)},
cin = {C020},
ddc = {610},
cid = {I:(DE-He78)C020-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37862240},
doi = {10.1093/jncics/pkad088},
url = {https://inrepo02.dkfz.de/record/284938},
}