{"doi":"10.1007/s10654-023-01048-7","title":"Polymorphisms in genes of melatonin biosynthesis and signaling support the light-at-night hypothesis for breast cancer","abstract":"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. rs1386483 R ∧ rs1473473 D ∧ rs3729931 D : 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.","journal":"European Journal of Epidemiology","year":2023,"id":364617,"datarank":0.31191623125197543,"base_score":2.0794415416798357,"endowment":2.0794415416798357,"self_citation_contribution":0.31191623125197543,"citation_network_contribution":0.0,"self_endowment_contribution":0.31191623125197543,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":524955,"name":"Reiner Hoppe","orcid":"0000-0003-2213-9612","position":1,"is_corresponding":false},{"id":1119734,"name":"Katja Ickstadt","orcid":"0000-0001-5157-2496","position":2,"is_corresponding":false},{"id":514992,"name":"Thomas Behrens","orcid":"0000-0002-4583-5234","position":3,"is_corresponding":false},{"id":348262,"name":"Stefan Winter","orcid":"0000-0002-5267-0255","position":4,"is_corresponding":false},{"id":1119735,"name":"Robert Herold","orcid":"0000-0002-0828-8745","position":5,"is_corresponding":false},{"id":1120204,"name":"Claudia Terschüren","orcid":null,"position":6,"is_corresponding":false},{"id":796697,"name":"Wing‐Yee Lo","orcid":null,"position":7,"is_corresponding":false},{"id":55327,"name":"Pascal Guénel","orcid":"0000-0002-8359-518X","position":8,"is_corresponding":false},{"id":55366,"name":"Thérèse Truong","orcid":"0000-0002-2943-6786","position":9,"is_corresponding":false},{"id":55306,"name":"Manjeet K. Bolla","orcid":"0000-0002-4351-9326","position":10,"is_corresponding":false},{"id":225487,"name":"Qin Wang","orcid":"0000-0002-9139-0627","position":11,"is_corresponding":false},{"id":55319,"name":"Joe Dennis","orcid":"0000-0003-4591-1214","position":12,"is_corresponding":false},{"id":55341,"name":"Kyriaki Michailidou","orcid":"0000-0001-7065-1237","position":13,"is_corresponding":false},{"id":249318,"name":"Michael Lush","orcid":"0000-0001-5945-3440","position":14,"is_corresponding":false},{"id":55303,"name":"Irene L. Andrulis","orcid":"0000-0002-4226-6435","position":15,"is_corresponding":false},{"id":22411,"name":"Hermann Brenner","orcid":"0000-0002-6129-1572","position":16,"is_corresponding":false},{"id":1027296,"name":"Jenny Chang-Claude","orcid":null,"position":17,"is_corresponding":false},{"id":55314,"name":"Angela Cox","orcid":"0000-0002-5138-1099","position":18,"is_corresponding":false},{"id":225513,"name":"Simon S. 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