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@ARTICLE{Wichert:284415,
author = {K. Wichert and R. Hoppe and K. Ickstadt and T. Behrens and
S. Winter and R. Herold and C. Terschüren and W.-Y. Lo and
P. Guénel and T. Truong and M. K. Bolla and Q. Wang and J.
Dennis and K. Michailidou and M. Lush and I. L. Andrulis and
H. Brenner$^*$ and J. Chang-Claude$^*$ and A. Cox and S. S.
Cross and K. Czene and M. Eriksson and J. D. Figueroa and M.
García-Closas and M. S. Goldberg and U. Hamann$^*$ and W.
He and B. Holleczek and J. L. Hopper and A. Jakubowska and
Y.-D. Ko and J. Lubiński and A. M. Mulligan and N. Obi and
V. Rhenius and M. Shah and X.-O. Shu and J. Simard and M. C.
Southey and W. Zheng and A. M. Dunning and P. D. P. Pharoah
and P. Hall and D. F. Easton and T. Brüning and H.
Brauch$^*$ and V. Harth and S. Rabstein},
title = {{P}olymorphisms in genes of melatonin biosynthesis and
signaling support the light-at-night hypothesis for breast
cancer.},
journal = {European journal of epidemiology},
volume = {38},
number = {10},
issn = {0393-2990},
address = {Dordrecht [u.a.]},
publisher = {Springer Science + Business Media B.V.},
reportid = {DKFZ-2023-02004},
pages = {1053-1068},
year = {2023},
note = {2023 Oct;38(10):1053-1068},
abstract = {Light-at-night triggers the decline of pineal gland
melatonin biosynthesis and secretion and is an
IARC-classified probable breast-cancer risk factor. We
applied a large-scale molecular epidemiology approach to
shed light on the putative role of melatonin in breast
cancer. We investigated associations between breast-cancer
risk and polymorphisms at genes of melatonin
biosynthesis/signaling using a study population of 44,405
women from the Breast Cancer Association Consortium (22,992
cases, 21,413 population-based controls). Genotype data of
97 candidate single nucleotide polymorphisms (SNPs) at 18
defined gene regions were investigated for breast-cancer
risk effects. We calculated adjusted odds ratios (ORs) and
$95\%$ confidence intervals (CI) by logistic regression for
the main-effect analysis as well as stratified analyses by
estrogen- and progesterone-receptor (ER, PR) status. SNP-SNP
interactions were analyzed via a two-step procedure based on
logic regression. The Bayesian false-discovery probability
(BFDP) was used for all analyses to account for multiple
testing. Noteworthy associations (BFDP < 0.8) included 10
linked SNPs in tryptophan hydroxylase 2 (TPH2) (e.g.
rs1386492: OR = 1.07, $95\%$ CI 1.02-1.12), and a SNP in the
mitogen-activated protein kinase 8 (MAPK8) (rs10857561: OR =
1.11, $95\%$ CI 1.04-1.18). The SNP-SNP interaction analysis
revealed noteworthy interaction terms with TPH2- and
MAPK-related SNPs (e.g. rs1386483R ∧ rs1473473D ∧
rs3729931D: OR = 1.20, $95\%$ CI 1.09-1.32). In line with
the light-at-night hypothesis that links shift work with
elevated breast-cancer risks our results point to SNPs in
TPH2 and MAPK-genes that may impact the intricate network of
circadian regulation.},
keywords = {Circadian rhythm (Other) / MAPK8 (Other) / Serotonin
biosynthesis (Other) / Shift work (Other) / TPH2 (Other)},
cin = {C070 / C120 / HD01 / C020 / B072 / TU01},
ddc = {610},
cid = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
I:(DE-He78)HD01-20160331 / I:(DE-He78)C020-20160331 /
I:(DE-He78)B072-20160331 / I:(DE-He78)TU01-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37789226},
doi = {10.1007/s10654-023-01048-7},
url = {https://inrepo02.dkfz.de/record/284415},
}