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@ARTICLE{Fedirko:144642,
author = {V. Fedirko and H. B. Mandle and W. Zhu and D. J. Hughes and
A. Siddiq and P. Ferrari and I. Romieu and E. Riboli and B.
Bueno-de-Mesquita and F. J. B. van Duijnhoven and P. D.
Siersema and A. Tjønneland and A. Olsen and V. Perduca and
F. Carbonnel and M.-C. Boutron-Ruault and T. Kühn$^*$ and
T. Johnson$^*$ and A. Krasimira and A. Trichopoulou and P.
Makrythanasis and D. Thanos and S. Panico and V. Krogh and
C. Sacerdote and G. Skeie and E. Weiderpass and S.
Colorado-Yohar and N. Sala and A. Barricarte and M.-J.
Sanchez and R. Quirós and P. Amiano and B. Gylling and S.
Harlid and A. Perez-Cornago and A. K. Heath and K. K.
Tsilidis and A. Dagfinn and H. Freisling and N. Murphy and
M. J. Gunter and M. Jenab},
title = {{V}itamin {D}-{R}elated {G}enes, {B}lood {V}itamin {D}
{L}evels and {C}olorectal {C}ancer {R}isk in {W}estern
{E}uropean {P}opulations.},
journal = {Nutrients},
volume = {11},
number = {8},
issn = {2072-6643},
address = {Basel},
publisher = {MDPI},
reportid = {DKFZ-2019-02084},
pages = {1954},
year = {2019},
abstract = {Higher circulating 25-hydroxyvitamin D levels (25(OH)D)
have been found to be associated with lower risk for
colorectal cancer (CRC) in prospective studies. Whether this
association is modified by genetic variation in genes
related to vitamin D metabolism and action has not been well
studied in humans. We investigated 1307 functional and
tagging single-nucleotide polymorphisms (SNPs; individually,
and by gene/pathway) in 86 vitamin D-related genes in 1420
incident CRC cases matched to controls from the European
Prospective Investigation into Cancer and Nutrition (EPIC)
cohort. We also evaluated the association between these SNPs
and circulating 25(OH)D in a subset of controls. We
confirmed previously reported CRC risk associations between
SNPs in the VDR, GC, and CYP27B1 genes. We also identified
additional associations with 25(OH)D, as well as CRC risk,
and several potentially novel SNPs in genes related to
vitamin D transport and action (LRP2, CUBN, NCOA7, and
HDAC9). However, none of these SNPs were statistically
significant after Benjamini-Hochberg (BH) multiple testing
correction. When assessed by a priori defined functional
pathways, tumor growth factor β (TGFβ) signaling was
associated with CRC risk (P ≤ 0.001), with most
statistically significant genes being SMAD7 (PBH = 0.008)
and SMAD3 (PBH = 0.008), and 18 SNPs in the vitamin D
receptor (VDR) binding sites (P = 0.036). The 25(OH)D-gene
pathway analysis suggested that genetic variants in the
genes related to VDR complex formation and transcriptional
activity are associated with CRC depending on 25(OH)D levels
(interaction P = 0.041). Additional studies in large
populations and consortia, especially with measured
circulating 25(OH)D, are needed to confirm our findings.},
cin = {C020},
ddc = {610},
cid = {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:31434255},
doi = {10.3390/nu11081954},
url = {https://inrepo02.dkfz.de/record/144642},
}