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

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  • David J. Hughes
  • Lutz Schomburg
  • Mazda Jenab
  • Carine Biessy
  • Catherine Méplan
  • Aurelie Moskal
  • Qian Sun
  • Kamil Demircan
  • Veronika Fedirko
  • Elisabete Weiderpass
  • Maryam Mukhtar
  • Anja Olsen
  • Kim Overvad
  • Matthias Schulze
  • Therese Haugdahl Nøst
  • Guri Skeie
  • Karina Standahl Olsen
  • Fulvio Ricceri
  • Sara Grioni
  • Domenico Palli
  • Giovanna Masala
  • Rosario Tumino
  • Fabrizio Pasanisi
  • Pilar Amiano
  • Sandra M. Colorado Yohar
  • Antonio Agudo
  • Maria Jose Sánchez
  • Eva Ardanaz
  • Malin Sund
  • Anne Andersson
  • Aurora Perez-Cornago
  • Ruth Travis
  • Alicia K. Heath
  • Laure Dossus
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, Ptrend = 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.
OriginalsprogEngelsk
TidsskriftFree Radical Biology and Medicine
Vol/bind209
Sider (fra-til)381-393
Antal sider13
ISSN0891-5849
DOI
StatusUdgivet - 2023

Bibliografisk note

Funding Information:
Funding for this study was provided by the Health Research Board of Ireland health research award HRA-PHS/2015/1142 (principal investigator: D.J.H.). L.S. was supported by Deutsche Forschungsgemeinschaft (DFG Research Unit 2558 TraceAge, Scho 849/6–2). We thank the members of EPIC and the study participants for their contributions to the EPIC cohort study. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark); Ligue Contre le Cancer, Institut Gustave Roussy, Mutuelle Générale de l'Education Nationale, Institut National de la Santé et de la Recherche Médicale (INSERM) (France); German Cancer Aid, German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, Compagnia di SanPaolo and National Research Council (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS), Netherlands Cancer Registry (NKR), LK Research Funds, Dutch Prevention Funds, Dutch ZON (Zorg Onderzoek Nederland), World Cancer Research Fund (WCRF), Statistics Netherlands (The Netherlands); Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain); Swedish Cancer Society, Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council (1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), (United Kingdom). We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands, for their contribution and ongoing support to the EPIC Study.

Funding Information:
Funding for this study was provided by the Health Research Board of Ireland health research award HRA-PHS/2015/1142 (principal investigator: D.J.H.). L.S. was supported by Deutsche Forschungsgemeinschaft (DFG Research Unit 2558 TraceAge, Scho 849/6–2). We thank the members of EPIC and the study participants for their contributions to the EPIC cohort study. The coordination of EPIC is financially supported by International Agency for Research on Cancer (IARC) and by the Department of Epidemiology and Biostatistics , School of Public Health, Imperial College London which has additional infrastructure support provided by the NIHR Imperial Biomedical Research Centre (BRC). The national cohorts are supported by: Danish Cancer Society (Denmark) ; Ligue Contre le Cancer , Institut Gustave Roussy , Mutuelle Générale de l’Education Nationale , Institut National de la Santé et de la Recherche Médicale (INSERM) (France) ; German Cancer Aid , German Cancer Research Center (DKFZ), German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE), Federal Ministry of Education and Research (BMBF) (Germany); Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy , Compagnia di SanPaolo and National Research Council (Italy) ; Dutch Ministry of Public Health, Welfare and Sports (VWS) , Netherlands Cancer Registry (NKR) , LK Research Funds , Dutch Prevention Funds , Dutch ZON (Zorg Onderzoek Nederland) , World Cancer Research Fund (WCRF) , Statistics Netherlands (The Netherlands) ; Health Research Fund (FIS) - Instituto de Salud Carlos III (ISCIII), Regional Governments of Andalucía, Asturias, Basque Country, Murcia and Navarra, and the Catalan Institute of Oncology - ICO (Spain) ; Swedish Cancer Society , Swedish Research Council and County Councils of Skåne and Västerbotten (Sweden) ; Cancer Research UK ( 14136 to EPIC-Norfolk; C8221/A29017 to EPIC-Oxford), Medical Research Council ( 1000143 to EPIC-Norfolk; MR/M012190/1 to EPIC-Oxford), (United Kingdom). We thank the National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands , for their contribution and ongoing support to the EPIC Study.

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© 2023 The Authors

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