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@ARTICLE{Thomas:293599,
author = {C. E. Thomas and Y. Lin and M. Kim and E. S. Kawaguchi and
C. Qu and C. Y. Um and B. M. Lynch and B. Van Guelpen and K.
Tsilidis and R. Carreras-Torres and F. J. van Duijnhoven and
L. C. Sakoda and P. T. Campbell and Y. Tian and J.
Chang-Claude$^*$ and S. Bézieau and A. Budiarto and J. R.
Palmer and P. A. Newcomb and G. Casey and L. Le Marchand and
M. Giannakis and C. I. Li and A. Gsur and C. Newton and M.
Obón-Santacana and V. Moreno and P. Vodicka and H.
Brenner$^*$ and M. Hoffmeister$^*$ and A. J. Pellatt and R.
E. Schoen and N. Dimou and N. Murphy and M. J. Gunter and S.
Castellví-Bel and J. C. Figueiredo and A. T. Chan and M.
Song and L. Li and D. T. Bishop and S. B. Gruber and J. W.
Baurley and S. A. Bien and D. V. Conti and J. R. Huyghe and
A. Kundaje and Y.-R. Su and J. Wang and T. O. Keku and M. O.
Woods and S. I. Berndt and S. J. Chanock and C. M. Tangen
and A. Wolk and A. Burnett-Hartman and A. H. Wu and E. White
and M. A. Devall and V. Díez-Obrero and D. A. Drew and E.
Giovannucci and A. Hidaka and A. E. Kim and J. P. Lewinger
and J. Morrison and J. Ose and N. Papadimitriou and B.
Pardamean and A. R. Peoples and E. A. Ruiz-Narvaez and A.
Shcherbina and M. C. Stern and X. Chen and D. C. Thomas and
E. A. Platz and W. J. Gauderman and U. Peters and L. Hsu},
title = {{C}haracterization of additive gene-environment
interactions for colorectal cancer risk.},
journal = {Epidemiology},
volume = {36},
number = {1},
issn = {1044-3983},
address = {Baltimore, Md.},
publisher = {Wolters Kluwer Health, Lippincott Williams $\&$ Wilkins},
reportid = {DKFZ-2024-01916},
pages = {126-138},
year = {2025},
note = {2025 Jan 1;36(1):126-138},
abstract = {Colorectal cancer (CRC) is a common, fatal cancer.
Identifying subgroups who may benefit more from intervention
is of critical public health importance. Previous studies
have assessed multiplicative interaction between genetic
risk scores and environmental factors, but few have assessed
additive interaction, the relevant public health
measure.Using resources from colorectal cancer consortia
including 45,247 CRC cases and 52,671 controls, we assessed
multiplicative and additive interaction (relative excess
risk due to interaction, RERI) using logistic regression
between 13 harmonized environmental factors and genetic risk
score including 141 variants associated with CRC risk.There
was no evidence of multiplicative interaction between
environmental factors and genetic risk score. There was
additive interaction where, for individuals with high
genetic susceptibility, either heavy drinking [RERI = 0.24,
$95\%$ confidence interval, CI, (0.13, 0.36)], ever smoking
[0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13),
male 0.10 (0.05, 0.14)], or high red meat intake [highest
versus lowest quartile 0.18 (0.09, 0.27)] was associated
with excess CRC risk greater than that for individuals with
average genetic susceptibility. Conversely, we estimate
those with high genetic susceptibility may benefit more from
reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20,
-0.11)] or higher intake of fruit, fiber, or calcium
[highest quartile versus lowest quartile -0.12 (-0.18,
-0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05),
respectively] than those with average genetic
susceptibility.Additive interaction is important to assess
for identifying subgroups who may benefit from intervention.
The subgroups identified in this study may help inform
precision CRC prevention.},
cin = {C020 / C070 / C120 / HD01},
ddc = {610},
cid = {I:(DE-He78)C020-20160331 / I:(DE-He78)C070-20160331 /
I:(DE-He78)C120-20160331 / I:(DE-He78)HD01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:39316822},
doi = {10.1097/EDE.0000000000001795},
url = {https://inrepo02.dkfz.de/record/293599},
}