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Lookup NU author(s): Dr Catherine Meplan
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
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.
Author(s): Hughes DJ, Schomburg L, Jenab M, Biessy C, Méplan C, Moskal A, Sun Q, Demircan K, Fedirko V, Weiderpass E, Mukhtar M, Olsen A, Tjønneland A, Overvad K, Schulze M, Haugdahl Nøst T, Skeie G, Standahl Olsen K, Ricceri F, Grioni S, Palli D, Masala G, Tumino R, Pasanisi F, Amiano P, Colorado Yohar SM, Agudo A, Sánchez MJ, Ardanaz E, Sund M, Andersson A, Perez-Cornago A, Travis R, Heath AK, Dossus L
Publication type: Article
Publication status: Published
Journal: Free Radical Biology & Medicine
Year: 2023
Volume: 209
Issue: 2
Pages: 381-393
Print publication date: 10/11/2023
Online publication date: 01/11/2023
Acceptance date: 19/10/2023
Date deposited: 27/02/2024
ISSN (print): 0891-5849
ISSN (electronic): 1873-4596
Publisher: Elsevier Inc.
URL: https://doi.org/10.1016/j.freeradbiomed.2023.10.401
DOI: 10.1016/j.freeradbiomed.2023.10.401
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