Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study.

Sandra M Colorado Yohar, Karina Standahl Olsen, Fulvio Ricceri, Sara Grioni, Domenico Palli, Giovanna Masala, Rosario Tumino, Fabrizio Pasanisi, Pilar Amiano, Guri Skeie, Antonio Agudo, Maria-Jose Sánchez, Eva Ardanaz, Malin Sund, Anne Andersson, Aurora Perez-Cornago, Ruth Travis, Laure Dossus, Veronika Fedirko, David J Hughes, Lutz Schomburg, Mazda Jenab, Carine Biessy, Catherine Méplan, Aurelie Moskal, Qian Sun, Kamil Demircan, Alicia K Heath, Elisabete Weiderpass, Maryam Mukhtar, Anja Olsen, Anne Tjønneland, Kim Overvad, Matthias Schulze, Therese Haugdahl Nøst

Journal: Free radical biology & medicine 2023;209(Pt 2):381-393

PMID: 37923090

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Abstract

Selenium (Se) may help prevent breast cancer (BC) development. Owing to limited observational evidence, we investigated whether prediagnostic Se status and/or variants in the selenoprotein genes are associated with BC risk in a large European cohort. Se status was assessed by plasma measures of Se and its major circulating proteins, selenoprotein P (SELENOP) and glutathione peroxidase 3 (GPX3), in matched BC case-control pairs (2208 for SELENOP; 1785 for GPX3 and Se) nested within the European Prospective Investigation into Cancer and Nutrition (EPIC). Single nucleotide polymorphisms (SNPs, n = 452) in 55 selenoprotein and Se metabolic pathway genes and an additional 18 variants previously associated with Se concentrations were extracted from existing genotyping data within EPIC for 1564 case-control pairs. Multivariable-adjusted logistic regression models were used to calculate the odds ratios (ORs) and 95 % confidence intervals (CIs) of the association between Se status markers, SNP variants and BC risk. Overall, there was no statistically significant association of Se status with BC risk. However, higher GPX3 activity was associated with lower risk of premenopausal BC (4th versus 1st quartile, OR = 0.54, 95 % CI: 0.30-0.98, P = 0.013). While none of the genetic variant associations (P ≤ 0.05) retained significance after multiple testing correction, rs1004243 in the SELENOM selenoprotein gene and two SNPs in the related antioxidant TXN2 gene (rs4821494 and rs5750261) were associated with respective lower and higher risks of BC at a significance threshold of P ≤ 0.01. Fourteen SNPs in twelve Se pathway genes (P ≤ 0.01) in interaction with Se status were also associated with BC risk. Higher Se status does not appear to be associated with BC risk, although activity of the selenoenzyme GPX3 may be inversely associated with premenopausal BC risk, and SNPs in the Se pathway alone or in combination with suboptimal Se status may influence BC risk.

Address: Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland. Electronic address: [email protected].; Institute for Experimental Endocrinology, Charité - Medical University, Berlin, Germany.; International Agency for Research on Cancer (IARC-WHO), Lyon, France.; School of Biomedical, Nutritional and Sport Sciences, Newcastle University, Newcastle Upon Tyne, UK.; International Agency for Research on Cancer (IARC-WHO), Lyon, France; Research on Healthcare Performance (RESHAPE), INSERM U1290, Université Claude Bernard Lyon 1, Lyon, France.; Department of Epidemiology, MD Anderson Cancer Centre, Houston, TX, USA.; Cancer Biology and Therapeutics Group, School of Biomolecular and Biomedical Science, UCD Conway Institute, University College Dublin, Dublin, Ireland.; Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Institute of Public Health, Aarhus University, Aarhus, Denmark.; Diet, Genes, and Environment, Danish Cancer Society Research Center, Copenhagen, Denmark; Institute of Public Health, University of Copenhagen, Copenhagen, Denmark.; Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark; Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.; Department of Molecular Epidemiology, German Institute of Human Nutrition, 14558, Nuthetal, Germany.; Department of Community Medicine, UiT the Arctic University of Norway, N-9037, Tromsø, Norway.; Department of Clinical and Biological Sciences, University of Turin, Turin, Italy; Unit of Epidemiology, Regional Health Service ASL TO3, Grugliasco, TO, Italy.; Epidemiology and Prevention Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori di Milano, 20133, Milano, Italy.; Cancer Risk Factors and Life-Style Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.; Hyblean Association for Epidemiological Research, AIRE ONLUS Ragusa, Italy.; Departiment Di Medicina Clinica E Chirurgia Federico Ii University, Naples, Italy.; Ministry of Health of the Basque Government, Sub Directorate for Public Health and Addictions of Gipuzkoa, San Sebastian, Spain; Biodonostia Health Research Institute, Epidemiology of Chronic and Communicable Diseases Group, San Sebastián, Spain; Spanish Consortium for Research on Epidemiology and Public Health (CIBERESP), Instituto de Salud Carlos III, Madrid, Spain.; Department of Epidemiology, Murcia Regional Health Council, IMIB, Murcia, Spain; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Research Group on Demography and Health, National Faculty of Public Health, University of Antioquia, Medellín, Colombia.; Unit of Nutrition and Cancer, Catalan Institute of Oncology - ICO, L'Hospitalet de Llobregat, Spain; Nutrition and Cancer Group, Epidemiology, Public Health, Cancer Prevention and Palliative Care Program, Bellvitge Biomedical Research Institute - IDIBELL, L'Hospitalet de Llobregat, Spain.; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Escuela Andaluza de Salud Pública (EASP), 18011, Granada, Spain; Instituto de Investigación Biosanitaria Ibs.GRANADA, 18012, Granada, Spain; Department of Preventive Medicine and Public Health, University of Granada, 18071, Granada, Spain.; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública (CIBERESP), Madrid, Spain; Navarra Public Health Institute, Pamplona, Spain; IdiSNA, Navarra Institute for Health Research, Pamplona, Spain.; Department of Surgery and Perioperative Sciences, Umeå University, Umeå, Sweden; Department of Surgery, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.; Department of Radiation Sciences/Oncology, Umeå University, Umeå, Sweden.; Cancer Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, OX3 7LF, UK.; Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, UK.

DOI: 10.1016/j.freeradbiomed.2023.10.401