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Wichert, Katharina; Hoppe, Reiner; Ickstadt, Katja; Behrens, Thomas; Winter, Stefan; Herold, Robert; Terschüren, Claudia; Lo, Wing-Yee; Guénel, Pascal; Truong, Thérèse; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Andrulis, Irene L.; Brenner, Hermann; Chang-Claude, Jenny; Cox, Angela; Cross, Simon S.; Czene, Kamila; Eriksson, Mikael; Figueroa, Jonine D.; García-Closas, Montserrat; [...]

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

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  • Medientyp: E-Artikel
  • Titel: Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer
  • Beteiligte: Wichert, Katharina; Hoppe, Reiner; Ickstadt, Katja; Behrens, Thomas; Winter, Stefan; Herold, Robert; Terschüren, Claudia; Lo, Wing-Yee; Guénel, Pascal; Truong, Thérèse; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Andrulis, Irene L.; Brenner, Hermann; Chang-Claude, Jenny; Cox, Angela; Cross, Simon S.; Czene, Kamila; Eriksson, Mikael; Figueroa, Jonine D.; García-Closas, Montserrat; [...]
  • Erschienen: Springer Science and Business Media LLC, 2023
  • Erschienen in: European Journal of Epidemiology
  • Sprache: Englisch
  • DOI: 10.1007/s10654-023-01048-7
  • ISSN: 0393-2990; 1573-7284
  • Schlagwörter: Epidemiology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>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 &lt; 0.8) included 10 linked SNPs in <jats:italic>tryptophan hydroxylase 2</jats:italic> (<jats:italic>TPH2</jats:italic>) (e.g. rs1386492: OR = 1.07, 95% CI 1.02–1.12), and a SNP in the <jats:italic>mitogen-activated protein kinase 8</jats:italic> (<jats:italic>MAPK8</jats:italic>) (rs10857561: OR = 1.11, 95% CI 1.04–1.18). The SNP-SNP interaction analysis revealed noteworthy interaction terms with <jats:italic>TPH2-</jats:italic> and MAPK-related SNPs (e.g. rs1386483<jats:sub><jats:italic>R</jats:italic></jats:sub> ∧ rs1473473<jats:sub><jats:italic>D</jats:italic></jats:sub> ∧ rs3729931<jats:sub><jats:italic>D</jats:italic></jats:sub>: 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 <jats:italic>TPH2</jats:italic> and MAPK-genes that may impact the intricate network of circadian regulation.</jats:p>