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 - 2023/11/20
Y1 - 2023/11/20
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
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U2 - 10.1016/j.freeradbiomed.2023.10.401
DO - 10.1016/j.freeradbiomed.2023.10.401
M3 - Article
C2 - 37923090
AN - SCOPUS:85176221883
SN - 0891-5849
VL - 209
SP - 381
EP - 393
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
ER -