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@ARTICLE{Wang:157054,
author = {X. Wang and Y.-R. Su and P. S. Petersen and S. Bien and S.
L. Schmit and D. A. Drew and D. Albanes and S. I. Berndt and
H. Brenner$^*$ and P. T. Campbell and G. Casey and J.
Chang-Claude$^*$ and S. Gallinger and S. B. Gruber and R. W.
Haile and T. A. Harrison and M. Hoffmeister$^*$ and E. J.
Jacobs and M. A. Jenkins and A. D. Joshi and L. Li and Y.
Lin and N. M. Lindor and L. Le Marchand and V. Martín and
R. L. Milne and R. Maclnnis and V. Moreno and H. Nan and P.
A. Newcomb and J. D. Potter and G. Rennert and H. S. Rennert
and M. L. Slattery and S. N. Thibodeau and S. J. Weinstein
and M. O. Woods and A. T. Chan and E. White and L. Hsu and
U. Peters},
title = {{E}xploratory genome-wide interaction analysis of
non-steroidal anti-inflammatory drugs and predicted gene
expression on colorectal cancer risk.},
journal = {Cancer epidemiology, biomarkers $\&$ prevention},
volume = {29},
number = {9},
issn = {1538-7755},
address = {Philadelphia, Pa.},
publisher = {AACR},
reportid = {DKFZ-2020-01345},
pages = {1800-1808},
year = {2020},
note = {2020 Sep;29(9):1800-1808},
abstract = {Regular use of non-steroidal anti-inflammatory drugs
(NSAIDs) is associated with lower risk of colorectal cancer
(CRC). Genome-wide interaction analysis on single variants
(G×E) has identified several SNPs that may interact with
NSAIDs to confer CRC risk, but variations in gene expression
levels may also modify the effect of NSAID use. Therefore,
we tested interactions between NSAID use and predicted gene
expression levels in relation to CRC risk.Genetically
predicted gene expressions were tested for interaction with
NSAID use on CRC risk among 19,258 CRC cases and 18,597
controls from 21 observational studies. A Mixed Score Test
for Interactions (MiSTi) approach was used to jointly assess
G×E effects which are modeled via fixed interaction effects
of the weighted burden within each gene sets (burden) and
residual G×E effects (variance). A false discovery rate
(FDR) at 0.2 was applied to correct for multiple
testing.Among the 4,840 genes tested, genetically predicted
expression levels of four genes modified the effect of any
NSAID use on CRC risk, including DPP10 (P-G×E=1.96×10-4),
KRT16 (P-G×E=2.3×10-4), CD14 (P-G×E=9.38×10-4), and
CYP27A1 (P-G×E=1.44×10-3). There was a significant
interaction between expression level of RP11-89N17 and
regular use of aspirin only on CRC risk (P-G×E=3.23×10-5).
No interactions were observed between predicted gene
expression and non-aspirin NSAID use at FDR<0.2.By
incorporating functional information, we discovered several
novel genes that interacted with NSAID use.These findings
provide preliminary support that could help understand the
chemopreventive mechanisms of NSAIDs on CRC.},
cin = {C070 / C020 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C020-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32651213},
doi = {10.1158/1055-9965.EPI-19-1018},
url = {https://inrepo02.dkfz.de/record/157054},
}