title: Association between polymorphisms in glutathione peroxidase and selenoprotein P genes, glutathione peroxidase activity, HRT use and breast cancer risk.
abstract: 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.
authors.affiliation: Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle-upon-Tyne, United Kingdom ; Human Nutrition Research Centre, Newcastle University, Newcastle-upon-Tyne, United Kingdom.
authors.forename: Catherine
authors.initials: C
authors.lastname: Méplan
authors.forename: Lars Ove
authors.initials: LO
authors.lastname: Dragsted
authors.forename: Gitte
authors.initials: G
authors.lastname: Ravn-Haren
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
authors.forename: John
authors.initials: J
authors.lastname: Hesketh
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D008875:Middle Aged; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051149:Selenoprotein P / Q000235:genetics*; D013482:Superoxide Dismutase / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D005979:Glutathione Peroxidase; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D051149:Selenoprotein P; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C117436:GPX2 protein, human
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Jan;13(1):146-9
references.pmid: 14744747
references.citation: PLoS One. 2011;6(11):e27642
references.pmid: 22110703
references.citation: Cancer Epidemiol Biomarkers Prev. 2004 Nov;13(11 Pt 1):1821-2
references.pmid: 15533915
references.citation: Cancer Res. 2008 Dec 15;68(24):10171-7
references.pmid: 19074884
references.citation: CA Cancer J Clin. 2011 Mar-Apr;61(2):69-90
references.pmid: 21296855
references.citation: Am J Clin Nutr. 2008 Apr;87(4):1019-27
references.pmid: 18400727
references.citation: Cancer Epidemiol Biomarkers Prev. 2010 Nov;19(11):2958-68
references.pmid: 20852007
references.citation: FASEB J. 2007 Oct;21(12):3063-74
references.pmid: 17536041
references.citation: J Nutr. 2005 Dec;135(12 Suppl):3021S-3024S
references.pmid: 16317164
references.citation: Annu Rev Pharmacol Toxicol. 1996;36:203-32
references.pmid: 8725388
references.citation: Histopathology. 1991 Nov;19(5):403-10
references.pmid: 1757079
references.citation: Biochem J. 2004 Aug 1;381(Pt 3):841-6
references.pmid: 15117283
references.citation: J Clin Oncol. 2007 Jul 20;25(21):3015-23
references.pmid: 17634480
references.citation: Breast Cancer Res Treat. 2010 Nov;124(2):425-31
references.pmid: 20306294
references.citation: Cancer Epidemiol Biomarkers Prev. 2005 Oct;14(10):2459-61
references.pmid: 16214934
references.citation: Hum Genet. 2008 Aug;124(1):31-42
references.pmid: 18575892
references.citation: Crit Rev Food Sci Nutr. 2013;53(1):49-75
references.pmid: 23035920
references.citation: J Mol Med (Berl). 1996 Jun;74(6):297-312
references.pmid: 8862511
references.citation: Blood Cells Mol Dis. 2002 Sep-Oct;29(2):174-8
references.pmid: 12490284
references.citation: Proc Nutr Soc. 2002 May;61(2):203-15
references.pmid: 12133202
references.citation: Nucleic Acids Res. 1988 Feb 11;16(3):1215
references.pmid: 3344216
references.citation: J Nutr. 2004 Jan;134(1):173-8
references.pmid: 14704313
references.citation: Proc Nutr Soc. 2011 May 3;:1-9
references.pmid: 21557886
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1441-7
references.pmid: 19345254
references.citation: Biochem J. 2009 Jul 29;422(1):11-22
references.pmid: 19627257
references.citation: Oncology. 2003;64(3):227-31
references.pmid: 12697962
references.citation: Antioxid Redox Signal. 2000 Winter;2(4):903-17
references.pmid: 11213491
references.citation: Gene. 2012 Jun 15;501(2):89-103
references.pmid: 22525041
references.citation: Carcinogenesis. 2006 Apr;27(4):820-5
references.pmid: 16287877
references.citation: Carcinogenesis. 2004 Jan;25(1):3-9
references.pmid: 14514655
references.citation: BMC Cancer. 2006 Aug 31;6:217
references.pmid: 16945136
references.citation: Cancer Res. 1989 Mar 15;49(6):1475-80
references.pmid: 2924301
references.citation: Methods Mol Biol. 2012;863:343-58
references.pmid: 22359305
references.citation: Antioxid Redox Signal. 2009 Nov;11(11):2631-40
references.pmid: 19453253
references.citation: Br J Nutr. 2009 Dec;102 Suppl 1:S38-55
references.pmid: 20100367
references.citation: Carcinogenesis. 2010 Jun;31(6):1074-9
references.pmid: 20378690
references.citation: Hum Mol Genet. 2008 Oct 15;17(R2):R109-15
references.pmid: 18852198
references.citation: Mutat Res. 2009 May 12;664(1-2):13-9
references.pmid: 19428376
references.citation: Carcinogenesis. 2007 Feb;28(2):427-34
references.pmid: 16959787
references.citation: Cancer Res. 2000 Nov 15;60(22):6381-3
references.pmid: 11103801
references.citation: Dtsch Arztebl Int. 2011 May;108(19):323-30
references.pmid: 21637635
references.citation: Ann Clin Biochem. 2012 Mar;49(Pt 2):152-8
references.pmid: 22130631
references.citation: J Natl Cancer Inst Monogr. 2000;(27):67-73
references.pmid: 10963620
references.citation: Breast Cancer Res Treat. 2011 Jun;127(2):309-24
references.pmid: 21445572
references.citation: Carcinogenesis. 2006 Apr;27(4):840-7
references.pmid: 16344274
references.citation: J Am Coll Nutr. 2003 Feb;22(1):43-51
references.pmid: 12569113
references.citation: Br J Cancer. 2006 Sep 18;95(6):674-6
references.pmid: 16880784
references.citation: Blood Cells Mol Dis. 2000 Oct;26(5):423-6
references.pmid: 11112379
references.citation: Cancer Lett. 2012 Feb 1;315(1):59-68
references.pmid: 22050908
references.citation: Cancer Epidemiol Biomarkers Prev. 2003 Feb;12(2):170-1
references.pmid: 12582029
references.citation: Cancer Lett. 2010 Sep 28;295(2):191-7
references.pmid: 20350778
references.citation: Eur J Nutr. 2009 Sep;48(6):383-6
references.pmid: 19415410
references.citation: J Nutr Biochem. 2012 Jun;23(6):532-8
references.pmid: 21684133
references.citation: Cancer Res. 2003 Jun 15;63(12):3347-51
references.pmid: 12810669
references.citation: Biochim Biophys Acta. 2009 Nov;1790(11):1555-68
references.pmid: 19289149
references.citation: Cancer Biomark. 2010;7(1):39-46
references.pmid: 21045263