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Carcinogenesis Advance Access originally published online on November 14, 2005
Carcinogenesis 2006 27(4):820-825; doi:10.1093/carcin/bgi267
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© The Author 2005. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Associations between GPX1 Pro198Leu polymorphism, erythrocyte GPX activity, alcohol consumption and breast cancer risk in a prospective cohort study

Gitte Ravn-Haren *, Anja Olsen 1, Anne Tjønneland 1, Lars O. Dragsted, Bjørn A. Nexø 2, Håkan Wallin 3, Kim Overvad 4, Ole Raaschou-Nielsen 1 and Ulla Vogel 3

Department of Toxicology and Risk Assessment, Danish Institute for Food and Veterinary Research, Søborg, Denmark, 1 Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark, 2 Institute of Human Genetics, University of Aarhus, Aarhus, Denmark, 3 National Institute of Occupational Health, Copenhagen, Denmark, 4 Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark

* To whom correspondence should be addressed. Email: grh{at}dfvf.dk

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.


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