TY - JOUR

T1 - Prediagnostic selenium status, selenoprotein gene variants and association with breast cancer risk in a European cohort study

AU - Hughes, David J.

AU - Schomburg, Lutz

AU - Jenab, Mazda

AU - Biessy, Carine

AU - Méplan, Catherine

AU - Moskal, Aurelie

AU - Sun, Qian

AU - Demircan, Kamil

AU - Fedirko, Veronika

AU - Weiderpass, Elisabete

AU - Mukhtar, Maryam

AU - Olsen, Anja

AU - Tjønneland, Anne

AU - Overvad, Kim

AU - Schulze, Matthias

AU - Nøst, Therese Haugdahl

AU - Skeie, Guri

AU - Olsen, Karina Standahl

AU - Ricceri, Fulvio

AU - Grioni, Sara

AU - Palli, Domenico

AU - Masala, Giovanna

AU - Tumino, Rosario

AU - Pasanisi, Fabrizio

AU - Amiano, Pilar

AU - Colorado Yohar, Sandra M.

AU - Agudo, Antonio

AU - Sánchez, Maria Jose

AU - Ardanaz, Eva

AU - Sund, Malin

AU - Andersson, Anne

AU - Perez-Cornago, Aurora

AU - Travis, Ruth

AU - Heath, Alicia K.

AU - Dossus, Laure

N1 - Publisher Copyright: © 2023 The Authors

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Breast cancer risk

KW - Gene-nutrient interaction

KW - Glutathione peroxidase 3

KW - Selenium status

KW - Selenoprotein P

U2 - 10.1016/j.freeradbiomed.2023.10.401

DO - 10.1016/j.freeradbiomed.2023.10.401

M3 - Journal article

C2 - 37923090

AN - SCOPUS:85176221883

VL - 209

SP - 381

EP - 393

JO - Free Radical Biology & Medicine

JF - Free Radical Biology & Medicine

SN - 0891-5849

ER -