Lipid peroxidation and glutathione peroxidase activity relationship in breast cancer depends on functional polymorphism of GPX1

BMC Cancer

Research Article

Agnieszka Bukowska¹  Beata Peplonska¹  Wojciech Fendler²  Oskar Zambrano Quispe³  Michal Galicki³  Zbigniew Morawiec³  Edyta Reszka⁴  Ewa Jablonska⁴  Peter Gresner⁴  Edyta Wieczorek⁴  Jolanta Gromadzinska⁴  Wojciech Wasowicz⁴  Magdalena B. Krol⁴ 

[1] Department of Environmental Epidemiology, Nofer Institute of Occupational Medicine, 8 Sw. Teresy Str, Lodz, Poland;Department of Pediatrics, Oncology, Hematology and Diabetology, Medical University of Lodz, 36/50 Sporna Str, Lodz, Poland;Department of Surgical Oncology, Regional Cancer Center, Copernicus Memorial Hospital in Lodz, 62 Pabianicka Str, Lodz, Poland;Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, 8 Sw. Teresy Str, Lodz, Poland;

关键词: Breast cancer;    Lipid peroxidation;    Glutathione peroxidase;    GPX1;    Single nucleotide polymorphism;    Selenium;   

DOI  :  10.1186/s12885-015-1680-4

 received in 2015-07-03, accepted in 2015-10-02,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundSince targeting oxidative stress markers has been recently recognized as a novel therapeutic target in cancer, it is interesting to investigate whether genetic susceptibility may modify oxidative stress response in cancer. The aim of this study was to elucidate whether genetic polymorphism in the antioxidant enzymes is associated with lipid peroxidation in breast cancer.MethodsWe conducted a study among Polish women, including 136 breast cancer cases and 183 healthy controls. The analysis included genetic polymorphisms in five redox related genes: GPX1 (rs1050450), GPX4 (rs713041), SOD2 (rs4880), SEPP1 (rs3877899) and SEP15 (rs5859), lipid peroxidation, the activities of antioxidant enzymes determined in blood compartments as well as plasma concentration of selenium – an antioxidant trace element involved in cancer. Genotyping was performed using the Real Time PCR. Lipid peroxidation was expressed as plasma concentration of thiobarbituric acid reactive substances (TBARS) and measured with the spectrofluorometric method. Glutathione peroxidase activity was spectrophotometrically determined in erythrocytes (GPx1) and plasma (GPx3) by the use of Paglia and Valentine method. Spectrophotometric methods were employed to measure activity of cytosolic superoxide dismutase (SOD1) in erythrocytes (Beauchamp and Fridovich method) and ceruloplasmin (Cp) in plasma (Sunderman and Nomoto method). Plasma selenium concentration was determined using graphite furnace atomic absorption spectrophotometry.ResultsBreast cancer risk was significantly associated with GPX1 rs1050450 (Pro198Leu) polymorphism, showing a protective effect of variant (Leu) allele. As compared to the control subjects, lipid peroxidation and GPx1 activity were significantly higher in the breast cancer cases, whereas ceruloplasmin activity was decreased. After genotype stratification, both GPx1 activity and TBARS concentration were the highest in GPX1 Pro/Pro homozygotes affected by breast cancer. At the same time, there was a significant correlation between the level of lipid peroxidation and GPx1 activity among the cancer subjects possessing GPX1 Pro/Pro genotype (r = 0.3043; p = 0.0089), whereas such a correlation was completely absent in the cases carrying at least one GPX1 Leu allele as well as in the controls (regardless of GPX1 genotype).ConclusionsGPX1 polymorphism may be an important factor modifying oxidative stress response in breast cancer subjects. Further studies are needed to elucidate its potential clinical significance.

【 授权许可】

CC BY   
© Jablonska et al. 2015