Nitric Oxide, Lipid Peroxiode and Manganese Superoxide Dismutase with Its Genetic Polymorphism in Breast Cancer and Benign Breast Patients among Egyptian Population Sample

Breast cancers are potentially life threatening malignancies in women. Current evidence indicates that free radicals and mitochondrial DNA damage play a prominent role in the development of breast cancer. Manganese superoxide dismutase (MnSOD) is a major enzyme that is responsible for the detoxification of reactive oxygen species (ROS) in the mitochondria. One of the several metabolic pathways involved in breast carcinogenesis is the human polymorphism in the mitochondria targeting sequence Ala9Val of the MnSOD gene. It is hypothesized that the valine to alanine substitution seems to alter transport of the enzyme into the mitochondrion, changing its efficacy in fighting oxidative stress. The present study included 24 females with breast cancer, 27females with benign breast lesion and 23 female healthy controls. Whole blood samples were collected, part on heparin for DNA extraction which was used to assay MnSOD polymorphism by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. The other part of blood samples was collected on plain tunes and serum together with breast tissue samples were used for estimation of lipid peroxides (LP), nitric oxide (NO) and total superoxide dismutase (SOD) activity. The results of the study showed significant elevations of serum NO mean levels in breast cancer patients (53.57 ±10.6 μmol/l) compared to both control subjects (25.4 ±8.3 μmol/l) and patients with benign breast lesions (23.6 ±7.8 μmol/l), the latter mean level is not significantly different from that of controls. NO levels in breast cancer tissues (7.3±1.3 pmol /mg protein) were significantly higher compared to both control subjects (1.6 ±0.03 pmol /mg protein) and patients with benign breast lesions (3.3±0.7 pmol/mg protein), Also, the latter mean level is significantly higher compared to that of controls. Serum MDA levels in breast cancer patients (1.58 ±104 μmol/l) were not significantly different compared to both control subjects (0.9 ±0.7 μmol/l) and patients with benign breast lesions (1.07 ±0.62 μmol/l), MDA mean levels in breast cancer tissues (244.2±23.1 pmol /mg protein) were significantly higher compared to both control subjects (77.4 ±8.3 pmole /mg protein) and patients with benign breast lesions (91.2±91.2 pmole /mg protein), , the latter mean level is not significantly different from that of controls. Serum total SOD mean activity of breast cancer patients (145.4 ±24.6 U/l) was significantly lower compared to both control subjects (231.5 ±39.4 U/l) and patients 
with benign breast lesions (211.1 ±37.4 U/l), , the latter mean level is not significantly different from that of controls. Total SOD mean activity in breast cancer tissues (9.3±2.7 U/mg protein) were significantly lower compared to both control subjects (25.5 ±1.1 U/mg protein) and patients with benign breast lesions (23.1±2.3 U/mg protein), , the latter mean activity is not significantly different from that of controls.
Ala/Val genotype is the most prominent in the breast cancer women (66.7%) with odd ratio =2.63 (p<0.03) as compared to the Val/Val which was higher in control (69.6%).Conclusion: It could be concluded that the individual susceptibility to breast cancer may be modulated by MnSOD polymorphism, and the combination of genetic factors with the increase of the free radicals that induce lipid peroxidation decreasing activity of enzymatic antioxidants might play an important role in the pathogenesis of breast cancer.