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@ARTICLE{Xia:154193,
author = {Z. Xia and Y.-R. Su and P. Petersen and L. Qi and A. E. Kim
and }, , USC Norris Comprehensive Cancer Center, Keck School
of Medicine, University of Southern California, Los Angeles,
CA, USA. and J. C. Figueiredo and }, , USC Norris
Comprehensive Cancer Center, Keck School of Medicine,
University of Southern California, Los Angeles, CA, USA. |
Department of Medicine, Samuel Oschin Comprehensive Cancer
Institute, Cedars-Sinai Medical Center, Los Angeles, CA,
USA. and Y. Lin and H. Nan and L. C. Sakoda and D. Albanes
and S. I. Berndt and S. Bézieau and S. Bien and D. D.
Buchanan and G. Casey and A. T. Chan and D. V. Conti and },
, USC Norris Comprehensive Cancer Center, Keck School of
Medicine, University of Southern California, Los Angeles,
CA, USA. and D. A. Drew and S. J. Gallinger and W. J.
Gauderman and }, , USC Norris Comprehensive Cancer Center,
Keck School of Medicine, University of Southern California,
Los Angeles, CA, USA. and G. G. Giles and S. B. Gruber and
}, , USC Norris Comprehensive Cancer Center, Keck School of
Medicine, University of Southern California, Los Angeles,
CA, USA. and M. J. Gunter and M. Hoffmeister$^*$ and M. A.
Jenkins and A. D. Joshi and L. Le Marchand and J. P.
Lewinger and }, , USC Norris Comprehensive Cancer Center,
Keck School of Medicine, University of Southern California,
Los Angeles, CA, USA. and L. Li and N. M. Lindor and V.
Moreno and N. Murphy and R. Nassir and P. A. Newcomb and S.
Ogino and G. Rennert and M. Song and X. Wang and A. Wolk and
M. O. Woods and H. Brenner$^*$ and E. White and M. L.
Slattery and E. L. Giovannucci and J. Chang-Claude$^*$ and
P. D. P. Pharoah and L. Hsu and P. T. Campbell and U.
Peters},
title = {{F}unctional informed genome-wide interaction analysis of
body mass index, diabetes and colorectal cancer risk.},
journal = {Cancer medicine},
volume = {9},
number = {10},
issn = {2045-7634},
address = {Hoboken, NJ},
publisher = {Wiley},
reportid = {DKFZ-2020-00649},
pages = {3563-3573},
year = {2020},
note = {2020 May;9(10):3563-3573},
abstract = {Body mass index (BMI) and diabetes are established risk
factors for colorectal cancer (CRC), likely through
perturbations in metabolic traits (e.g. insulin resistance
and glucose homeostasis). Identification of interactions
between variation in genes and these metabolic risk factors
may identify novel biologic insights into CRC etiology.To
improve statistical power and interpretation for
gene-environment interaction (G × E) testing, we tested
genetic variants that regulate expression of a gene together
for interaction with BMI (kg/m2 ) and diabetes on CRC risk
among 26 017 cases and 20 692 controls. Each variant was
weighted based on PrediXcan analysis of gene expression data
from colon tissue generated in the Genotype-Tissue
Expression Project for all genes with heritability $≥1\%.$
We used a mixed-effects model to jointly measure the
G × E interaction in a gene by partitioning the
interactions into the predicted gene expression levels
(fixed effects), and residual G × E effects (random
effects). G × BMI analyses were stratified by sex as
BMI-CRC associations differ by sex. We used false discovery
rates to account for multiple comparisons and reported all
results with FDR <0.2.Among 4839 genes tested, genetically
predicted expressions of FOXA1 (P = 3.15 × 10-5 ),
PSMC5 (P = 4.51 × 10-4 ) and CD33 (P = 2.71 × 10-4
) modified the association of BMI on CRC risk for men;
KIAA0753 (P = 2.29 × 10-5 ) and SCN1B
(P = 2.76 × 10-4 ) modified the association of BMI on
CRC risk for women; and PTPN2 modified the association
between diabetes and CRC risk in both sexes
(P = 2.31 × 10-5 ).Aggregating G × E interactions
and incorporating functional information, we discovered
novel genes that may interact with BMI and diabetes on CRC
risk.},
cin = {C070 / C120 / C020},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)C020-20160331},
pnm = {313 - Cancer risk factors and prevention (POF3-313)},
pid = {G:(DE-HGF)POF3-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32207560},
doi = {10.1002/cam4.2971},
url = {https://inrepo02.dkfz.de/record/154193},
}