Journal Article

DKFZ-2023-02004

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer.

Wichert, K. ; Hoppe, R. ; Ickstadt, K. ; Behrens, T. ; Winter, S. ; Herold, R. ; Terschüren, C. ; Lo, W.-Y. ; Guénel, P. ; Truong, T. ; Bolla, M. K. ; Wang, Q. ; Dennis, J. ; Michailidou, K. ; Lush, M. ; Andrulis, I. L. ; Brenner, H.DKFZ* ; Chang-Claude, J.DKFZ* ; Cox, A. ; Cross, S. S. ; Czene, K. ; Eriksson, M. ; Figueroa, J. D. ; García-Closas, M. ; Goldberg, M. S. ; Hamann, U.DKFZ* ; He, W. ; Holleczek, B. ; Hopper, J. L. ; Jakubowska, A. ; Ko, Y.-D. ; Lubiński, J. ; Mulligan, A. M. ; Obi, N. ; Rhenius, V. ; Shah, M. ; Shu, X.-O. ; Simard, J. ; Southey, M. C. ; Zheng, W. ; Dunning, A. M. ; Pharoah, P. D. P. ; Hall, P. ; Easton, D. F. ; Brüning, T. ; Brauch, H.DKFZ* ; Harth, V. ; Rabstein, S.

2023
Springer Science + Business Media B.V. Dordrecht [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1007/s10654-023-01048-7

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.

Keyword(s): Circadian rhythm ; MAPK8 ; Serotonin biosynthesis ; Shift work ; TPH2

Note: 2023 Oct;38(10):1053-1068

---

Contributing Institute(s):

1. C070 Klinische Epidemiologie und Alternf. (C070)
2. Präventive Onkologie (C120)
3. DKTK HD zentral (HD01)
4. C020 Epidemiologie von Krebs (C020)
5. Molekulargenetik des Mammakarzinoms (B072)
6. DKTK Koordinierungsstelle Tübingen (TU01)

Research Program(s):

1. 313 - Krebsrisikofaktoren und Prävention (POF4-313) (POF4-313)

Appears in the scientific report 2023

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DEAL Springer ; DEAL Springer ; Essential Science Indicators ; IF >= 10 ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---