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@ARTICLE{Bouras:282365,
author = {E. Bouras and A. E. Kim and Y. Lin and J. Morrison and M.
Du and D. Albanes and E. L. Barry and J. W. Baurley and S.
I. Berndt and S. A. Bien and T. D. Bishop and H. Brenner$^*$
and A. Budiarto and A. Burnett-Hartman and P. T. Campbell
and R. Carreras-Torres and G. Casey and T. W. Cenggoro and
A. T. Chan and J. Chang-Claude$^*$ and D. V. Conti and M.
Cotterchio and M. Devall and V. Diez-Obrero and N. Dimou and
D. A. Drew and J. C. Figueiredo and G. G. Giles and S. B.
Gruber and M. J. Gunter and T. A. Harrison and A. Hidaka and
M. Hoffmeister$^*$ and J. R. Huyghe and A. D. Joshi and E.
S. Kawaguchi and T. O. Keku and A. Kundaje and L. Le
Marchand and J. P. Lewinger and L. Li and B. M. Lynch and B.
Mahesworo and S. Männistö and V. Moreno and N. Murphy and
P. A. Newcomb and M. Obón-Santacana and J. Ose and J. R.
Palmer and N. Papadimitriou and B. Pardamean and A. J.
Pellatt and A. R. Peoples and E. A. Platz and J. D. Potter
and L. Qi and C. Qu and G. Rennert and E. Ruiz-Narvaez and
L. C. Sakoda and S. L. Schmit and A. Shcherbina and M. C.
Stern and Y.-R. Su and C. M. Tangen and D. C. Thomas and Y.
Tian$^*$ and C. Y. Um and F. J. van Duijnhoven and B. Van
Guelpen and K. Visvanathan and J. Wang and E. White and A.
Wolk and M. O. Woods and C. M. Ulrich and L. Hsu and W. J.
Gauderman and U. Peters and K. K. Tsilidis},
title = {{G}enome-wide interaction analysis of folate for colorectal
cancer risk.},
journal = {The American journal of clinical nutrition},
volume = {118},
number = {5},
issn = {0095-9871},
address = {Oxford},
publisher = {Oxford University Press},
reportid = {DKFZ-2023-01747},
pages = {881-891},
year = {2023},
note = {2023 Nov;118(5):881-891},
abstract = {Epidemiological and experimental evidence suggests that
higher folate intake is associated with a decreased
colorectal cancer (CRC) risk; however, the mechanisms
underlying this relationship are not fully understood.
Genetic variation that may have a direct or indirect impact
on folate metabolism can provide insights into folate's role
in CRC.Our aim was to perform a genome-wide interaction
analysis to identify genetic variants that may modify the
association of folate on CRC risk.We applied traditional
case-control logistic regression, joint 3-degree of freedom
(3DF), and a two-step weighted hypothesis approach to test
the interactions of common variants (allele frequency
$>1\%)$ across the genome and dietary folate, folic acid
supplement use, and total folate in relation to risk of CRC,
in 30,550 cases and 42,336 controls from 51 studies from 3
genetic consortia (CCFR, CORECT, GECCO).Inverse associations
of dietary, total folate, and folic acid supplement with CRC
were found [odds ratio: 0.93 $(95\%$ confidence intervals
[CI]: 0.90-0.96), and 0.91 (0.89-0.94) per quartile higher
intake, and 0.82 (0.78-0.88) for users vs. non-users,
respectively]. Interactions (P-interaction <5×10-8) of
folic acid supplement and variants in the 3p25.2 locus [in
the region of Synapsin II (SYN2)/tissue inhibitor of
metalloproteinase 4 (TIMP4)] were found using the
traditional interaction analysis, with variant rs150924902
(located upstream to SYN2) showing the strongest
interaction. In stratified analyses by rs150924902
genotypes, folate supplement was associated with decreased
CRC risk among those carrying the TT genotype (OR = 0.82;
$95\%CI:$ 0.79-0.86) but increased CRC risk among those
carrying the TA genotype (OR = 1.63; $95\%CI:$ 1.29-2.05),
suggesting a qualitative interaction (P-interaction =
1.4×10-8). No interactions were observed for dietary and
total folate.Variation in 3p25.2 locus may modify the
association of folate supplement with CRC risk. Experimental
studies and studies incorporating other relevant -omics data
are warranted to validate this finding.},
keywords = {CRC (Other) / European (Other) / GWIS (Other) / SYN2
(Other) / TIMP4 (Other) / colorectal cancer (Other) / folate
(Other) / folic acid (Other) / genome-wide (Other) /
interaction (Other) / synapsin (Other) / tissue inhibitor of
metalloproteinase 4 (Other)},
cin = {C070 / C120 / HD01 / C020},
ddc = {570},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / 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:37640106},
doi = {10.1016/j.ajcnut.2023.08.010},
url = {https://inrepo02.dkfz.de/record/282365},
}
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