title: Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study.
abstract: Breast cancer may be related to oxidative stress. Breast cancer patients have been reported to have lower antioxidant enzyme activity than healthy controls and the polymorphism GPX1 Pro198Leu has been associated with risk of lung and breast cancer. The purpose of the present nested case-control study was to determine whether GPX1 Pro198Leu and glutathione peroxidase (GPX) activity in prospectively collected blood samples are associated with breast cancer risk among postmenopausal women and whether GPX activity levels are associated with other known breast cancer risk factors. We matched 377 female breast cancer cases with 377 controls all nested within the prospective 'Diet, Cancer and Health' study of 57 000 Danes. Carriers of the variant T-allele of GPX1 Pro198Leu were at 1.43-fold higher risk of breast cancer compared with non-carriers (95% CI=1.07-1.92). Pre-diagnostic GPX activity tended to be lower in cases compared with controls. GPX activity was positively correlated with intake of alcohol (P<0.0001) and the catalytic activity was lowered 5% for each additional copy of the variant T-allele (P=0.0003). Alcohol intake was correlated with increased GPX activity for the C-allele but not for the T-allele. Results from this prospective study suggest that the GPX1 Pro198Leu-associated lowered GPX activity is associated with higher breast cancer risk among Danish women.
authors.affiliation: Department of Toxicology and Risk Assessment, Danish Institute for Food and Veterinary Research, Søborg, Denmark. grh@dfvf.dk
authors.forename: Gitte
authors.initials: G
authors.lastname: Ravn-Haren
authors.forename: Anja
authors.initials: A
authors.lastname: Olsen
authors.forename: Anne
authors.initials: A
authors.lastname: Tjønneland
authors.forename: Lars O
authors.initials: LO
authors.lastname: Dragsted
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
authors.forename: Håkan
authors.initials: H
authors.lastname: Wallin
authors.forename: Kim
authors.initials: K
authors.lastname: Overvad
authors.forename: Ole
authors.initials: O
authors.lastname: Raaschou-Nielsen
authors.forename: Ulla
authors.initials: U
authors.lastname: Vogel
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000209:etiology* / Q000235:genetics*; D016022:Case-Control Studies; D003718:Denmark; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005979:Glutathione Peroxidase / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D012307:Risk Factors; D000094765:Glutathione Peroxidase GPX1
chemical_list: D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human