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Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer

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 associatio...

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Main Authors: Wichert, Katharina (Author) , Hoppe, Reiner (Author) , Ickstadt, Katja (Author) , Behrens, Thomas (Author) , Winter, Stefan (Author) , Herold, Robert (Author) , Terschüren, Claudia (Author) , Lo, Wing-Yee (Author) , Guénel, Pascal (Author) , Truong, Thérèse (Author) , Bolla, Manjeet K. (Author) , Wang, Qin (Author) , Dennis, Joe (Author) , Michailidou, Kyriaki (Author) , Lush, Michael (Author) , Andrulis, Irene L. (Author) , Brenner, Hermann (Author) , Chang-Claude, Jenny (Author) , Cox, Angela (Author) , Cross, Simon S. (Author) , Czene, Kamila (Author) , Eriksson, Mikael (Author) , Figueroa, Jonine D. (Author) , García-Closas, Montserrat (Author) , Goldberg, Mark S. (Author) , Hamann, Ute (Author) , He, Wei (Author) , Holleczek, Bernd (Author) , Hopper, John L. (Author) , Jakubowska, Anna (Author) , Ko, Yon-Dschun (Author) , Lubiński, Jan (Author) , Mulligan, Anna Marie (Author) , Obi, Nadia (Author) , Rhenius, Valerie (Author) , Shah, Mitul (Author) , Shu, Xiao-Ou (Author) , Simard, Jacques (Author) , Southey, Melissa C. (Author) , Zheng, Wei (Author) , Dunning, Alison M. (Author) , Pharoah, Paul D. P. (Author) , Hall, Per (Author) , Easton, Douglas F. (Author) , Brüning, Thomas (Author) , Brauch, Hiltrud (Author) , Harth, Volker (Author) , Rabstein, Sylvia (Author)
Format: Article (Journal)
Language:English
Published: 03 October 2023
In: European journal of epidemiology
Year: 2023, Volume: 38, Issue: 10, Pages: 1053-1068
ISSN:1573-7284
DOI:10.1007/s10654-023-01048-7
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1007/s10654-023-01048-7
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Author Notes:Katharina Wichert, Reiner Hoppe, Katja Ickstadt, Thomas Behrens, Stefan Winter, Robert Herold, Claudia Terschüren, Wing-Yee Lo, Pascal Guénel, Thérèse Truong, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Michael Lush, Irene L. Andrulis, Hermann Brenner, Jenny Chang-Claude, Angela Cox, Simon S. Cross, Kamila Czene, Mikael Eriksson, Jonine D. Figueroa, Montserrat García-Closas, Mark S. Goldberg, Ute Hamann, Wei He, Bernd Holleczek, John L. Hopper, Anna Jakubowska, Yon-Dschun Ko, Jan Lubiński, Anna Marie Mulligan, Nadia Obi, Valerie Rhenius, Mitul Shah, Xiao-Ou Shu, Jacques Simard, Melissa C. Southey, Wei Zheng, Alison M. Dunning, Paul D.P. Pharoah, Per Hall, Douglas F. Easton, Thomas Brüning, Hiltrud Brauch, Volker Harth, Sylvia Rabstein

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245 1 0 |a Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer  |c Katharina Wichert, Reiner Hoppe, Katja Ickstadt, Thomas Behrens, Stefan Winter, Robert Herold, Claudia Terschüren, Wing-Yee Lo, Pascal Guénel, Thérèse Truong, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Michael Lush, Irene L. Andrulis, Hermann Brenner, Jenny Chang-Claude, Angela Cox, Simon S. Cross, Kamila Czene, Mikael Eriksson, Jonine D. Figueroa, Montserrat García-Closas, Mark S. Goldberg, Ute Hamann, Wei He, Bernd Holleczek, John L. Hopper, Anna Jakubowska, Yon-Dschun Ko, Jan Lubiński, Anna Marie Mulligan, Nadia Obi, Valerie Rhenius, Mitul Shah, Xiao-Ou Shu, Jacques Simard, Melissa C. Southey, Wei Zheng, Alison M. Dunning, Paul D.P. Pharoah, Per Hall, Douglas F. Easton, Thomas Brüning, Hiltrud Brauch, Volker Harth, Sylvia Rabstein 
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520 |a 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. 
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