BACKGROUND: Mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide anion into H(2)O(2), which is neutralized sequentially by either catalase (CAT) or glutathione peroxidase 1 (Gpx 1) into water or converted into highly reactive hypochlorous acid by myeloperoxidase (MPO). We hypothesize that gene variants for these enzymes might be associated with the risk of breast cancer in non-smoking, non-alcohol-consuming women. METHODS: Genotypes of oxidative stress-related enzymes (MnSOD1183T>C, MPO-463G>A, GPx1Pro198Leu and CAT-262C>T) were analysed in 260 non-smoking and non-alcohol-consuming female patients with breast cancer and 224 habit-matched controls. RESULTS: Subjects with the MnSOD1183T>C C carrier or those with the GPx1Pro198Leu CT genotype had significantly decreased age-adjusted risks (odds ratio [OR]: 0.56 and 0.16 with 95% confidence intervals [95% CI]: 0.38-0.83 and 0.08-0.29, respectively) for breast cancer. Certain combined genotypes of the polymorphisms also significantly modulated the age-adjusted risk. CONCLUSIONS: We conclude that oxidative stress-related enzyme genetic variants, especially GPx1Pro198Leu CT, modify the risk of breast cancer development in non-smoking and non-alcohol-consuming women. The role of unidentified environmental factors predisposing to breast cancer development through an oxidative stress mechanism merits further investigation.
BACKGROUND: Mitochondrial manganese superoxide dismutase (MnSOD) converts superoxide anion into H(2)O(2), which is neutralized sequentially by either catalase (CAT) or glutathione peroxidase 1 (Gpx 1) into water or converted into highly reactive hypochlorous acid by myeloperoxidase (MPO). We hypothesize that gene variants for these enzymes might be associated with the risk of breast cancer in non-smoking, non-alcohol-consuming women. METHODS: Genotypes of oxidative stress-related enzymes (MnSOD1183T>C, MPO-463G>A, GPx1Pro198Leu and CAT-262C>T) were analysed in 260 non-smoking and non-alcohol-consuming female patients with breast cancer and 224 habit-matched controls. RESULTS: Subjects with the MnSOD1183T>C C carrier or those with the GPx1Pro198Leu CT genotype had significantly decreased age-adjusted risks (odds ratio [OR]: 0.56 and 0.16 with 95% confidence intervals [95% CI]: 0.38-0.83 and 0.08-0.29, respectively) for breast cancer. Certain combined genotypes of the polymorphisms also significantly modulated the age-adjusted risk. CONCLUSIONS: We conclude that oxidative stress-related enzyme genetic variants, especially GPx1Pro198Leu CT, modify the risk of breast cancer development in non-smoking and non-alcohol-consuming women. The role of unidentified environmental factors predisposing to breast cancer development through an oxidative stress mechanism merits further investigation.
Authors: Patricia Rodrigues; Griselda de Marco; Jessica Furriol; Maria Luisa Mansego; Mónica Pineda-Alonso; Anna Gonzalez-Neira; Juan Carlos Martin-Escudero; Javier Benitez; Ana Lluch; Felipe J Chaves; Pilar Eroles Journal: BMC Cancer Date: 2014-11-21 Impact factor: 4.430
Authors: Cheng-Di Wang; Yan Sun; Nan Chen; Lin Huang; Jing-Wen Huang; Min Zhu; Ting Wang; Yu-Lin Ji Journal: Sci Rep Date: 2016-05-26 Impact factor: 4.379
Authors: Jimmy Belotte; Nicole M Fletcher; Mohammed G Saed; Mohammed S Abusamaan; Gregory Dyson; Michael P Diamond; Ghassan M Saed Journal: PLoS One Date: 2015-08-24 Impact factor: 3.240
Authors: Catherine Méplan; Lars Ove Dragsted; Gitte Ravn-Haren; Anne Tjønneland; Ulla Vogel; John Hesketh Journal: PLoS One Date: 2013-09-10 Impact factor: 3.240