Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 9...

Full description

Bibliographic Details
Main Authors:	Méplan, Catherine, Dragsted, Lars Ove, Ravn-Haren, Gitte, Tjønneland, Anne, Vogel, Ulla, Hesketh, John
Format:	Online
Language:	English
Published:	Public Library of Science 2013
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769272/

id	pubmed-3769272
recordtype	oai_dc
spelling	pubmed-37692722013-09-13 Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk Méplan, Catherine Dragsted, Lars Ove Ravn-Haren, Gitte Tjønneland, Anne Vogel, Ulla Hesketh, John Research Article Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ∼2 fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use, eGPx activity was significantly lower in women who developed BC later in life compared with controls. Furthermore, GPx1 protein levels increased in human breast adenocarcinoma MCF7 cells exposed to β-estradiol and sodium selenite.In conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by estrogens. Our data thus suggest a role of selenoproteins in BC development. Public Library of Science 2013-09-10 /pmc/articles/PMC3769272/ /pubmed/24039907 http://dx.doi.org/10.1371/journal.pone.0073316 Text en © 2013 Méplan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Méplan, Catherine Dragsted, Lars Ove Ravn-Haren, Gitte Tjønneland, Anne Vogel, Ulla Hesketh, John
spellingShingle	Méplan, Catherine Dragsted, Lars Ove Ravn-Haren, Gitte Tjønneland, Anne Vogel, Ulla Hesketh, John Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
author_facet	Méplan, Catherine Dragsted, Lars Ove Ravn-Haren, Gitte Tjønneland, Anne Vogel, Ulla Hesketh, John
author_sort	Méplan, Catherine
title	Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
title_short	Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
title_full	Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
title_fullStr	Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
title_full_unstemmed	Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk
title_sort	association between polymorphisms in glutathione peroxidase and selenoprotein p genes, glutathione peroxidase activity, hrt use and breast cancer risk
description	Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ∼2 fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use, eGPx activity was significantly lower in women who developed BC later in life compared with controls. Furthermore, GPx1 protein levels increased in human breast adenocarcinoma MCF7 cells exposed to β-estradiol and sodium selenite.In conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by estrogens. Our data thus suggest a role of selenoproteins in BC development.
publisher	Public Library of Science
publishDate	2013
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3769272/
_version_	1612010635538726912

Association between Polymorphisms in Glutathione Peroxidase and Selenoprotein P Genes, Glutathione Peroxidase Activity, HRT Use and Breast Cancer Risk

Similar Items