the Effect of oxidative stress on tumor suppressor protein p53 and some biochemical markers in breast cancer patients in Erbil governorate

  • Ashtee Abdulkareem Ahmad Department of Chemistry, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
  • Kamaran Abdoulrahman Department of Chemistry, College of Science, Salahaddin University-Erbil, Kurdistan Region, Iraq
Keywords: Reactive oxygen species; Oxidative stress; breast cancer; tumor suppressor protein p53; Liver function; renal function.‎


The present study was conducted to observe the effect and association of oxidative stress on breast cancer, as well as evaluate the alteration of the serum lipid profile, hepatic and kidney biomarkers and serum tumor suppressor protein p53 in breast cancer patients in female as an important objective and determine the relationship between serum p53 with nitric oxide NO, malondialdehyde MDA, superoxide dismutase SOD, lipid profile, liver and kidney functions. In this study 80 subjects were conducted 50 women who had breast cancer as a patient group, and 30 healthy women were conducted as a control group. Blood samples were taken from both patients and control group, who were aged between (18-75) years old. The results of this study revealed that the median levels of serum NO, creatinine and the mean level of serum HDL are significantly lower in patients group with breast cancer than those in control group. Whereas, the median levels of serum MDA, TG, LDL, ALT, AST, and the mean level of serum CH are significantly higher in patients group with breast cancer rather than in control group. While, there are negative weak significant correlations between p53 with MDA, CH, TG and ALT. ROC curve analysis exhibit that serum NO, MDA, TG, HDL, ALT and AST are excellent biomarkers for the diagnostic accuracy of breast cancer in female as a result of the high level of AUC. Whereas, this study demonstrates that serum p53 is not a good biomarker for female breast cancer with AUC value 0.5636. Although, it is known that serum p53 is a tumor suppressor protein that plays a crucial role in the inhibition of cancer development.

In conclusion, the results revealed that patients with breast cancer have a systemic oxidative stress rising due to human tumor cells produce large quantity of ROS, which plays a crucial role in liver diseases, abnormality of renal function and hyperlipidemia. Most possibly due to the endothelial dysfunction which consequently is risk factor for patient’s health.


ABDOULRAHMAN, K. 2017. Lipid profile, oxidative stress and homocysteine in chronic renal failure CRF patients pre- and post-hemodialysis in Erbil city. ZANCO JOURNAL OF PURE AND APPLIED SCIENCES, 29, 65-73.
ANNUK, M., SOVERI, I., ZILMER, M., LIND, L., HULTHE, J. & FELLSTRöM, B. 2005. Endothelial function, CRP and oxidative stress in chronic kidney disease. JN. Journal of Nephrology (Milano. 1992), 18, 721-726.
APEL, K. & HIRT, H. 2004. Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu. Rev. Plant Biol., 55, 373-399.
AYDIN, K., GUVEN, K. & OZBAY, E. Two-dimensional left-handed metamaterial with a negative refractive index. Journal of Physics: Conference Series, 2006. IOP Publishing, 6.
BAKER, M. A. & HE, S. 1991. Elaboration of cellular DNA breaks by hydroperoxides. Free Radical Biology and Medicine, 11, 563-572.
BECKMAN, J. S. & KOPPENOL, W. H. 1996. Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. American Journal of Physiology-Cell Physiology, 271, C1424-C1437.
CAPASSO, I., ESPOSITO, E., PENTIMALLI, F., CRISPO, A., MONTELLA, M., GRIMALDI, M., DE MARCO, M. R., CAVALCANTI, E., D’AIUTO, M. & FUCITO, A. 2010. Metabolic syndrome affects breast cancer risk in postmenopausal women: National Cancer Institute of Naples experience. Cancer biology & therapy, 10, 1240-1243.
CHEESEMAN, K. & SLATER, T. 1993. An introduction to free radical biochemistry. British medical bulletin, 49, 481-493.
CLARKE, A., PURDIE, C., HARRISON, D., MORRIS, R., BIRD, C., HOOPER, M. & WYLLIE, A. 1993. Thymocyte apoptosis induced by p53-dependent and independent pathways. Nature, 362, 849-852.
CONKLIN, K. A. 2004. Chemotherapy-associated oxidative stress: impact on chemotherapeutic effectiveness. Integrative cancer therapies, 3, 294-300.
DAS, N., MA, C. & SALMON, Y. 1987. The relationship of serum vitamin A, cholesterol, and triglycerides to the incidence of ovarian cancer. Biochemical medicine and metabolic biology, 37, 213-219.
DINIZ, Y. S., FERNANDES, A. A., CAMPOS, K. E., MANI, F., RIBAS, B. O. & NOVELLI, E. L. 2004. Toxicity of hypercaloric diet and monosodium glutamate: oxidative stress and metabolic shifting in hepatic tissue. Food and Chemical Toxicology, 42, 313-319.
ESPER, R. J., NORDABY, R. A., VILARIñO, J. O., PARAGANO, A., CACHARRóN, J. L. & MACHADO, R. A. 2006. Endothelial dysfunction: a comprehensive appraisal. Cardiovascular diabetology, 5, 4.
FLOHE, L., BECKMANN, R., GIERTZ, H. & LOSCHEN, G. 1985. Oxygen-centered free radicals as mediators of inflammation. Oxidative stress. Academic Press London.
FREEMAN, B. A. & CRAPO, J. D. 1982. Biology of disease: free radicals and tissue injury. Laboratory investigation; a journal of technical methods and pathology, 47, 412-426.
FURBERG, A.-S., JASIENSKA, G., BJURSTAM, N., TORJESEN, P. A., EMAUS, A., LIPSON, S. F., ELLISON, P. T. & THUNE, I. 2005. Metabolic and hormonal profiles: HDL cholesterol as a plausible biomarker of breast cancer risk. The Norwegian EBBA Study. Cancer Epidemiology and Prevention Biomarkers, 14, 33-40.
GöNENC, A., ERTEN, D., ASLAN, S., AKıNCı, M., ŞIMŞEK, B. & TORUN, M. 2006. Lipid peroxidation and antioxidant status in blood and tissue of malignant breast tumor and benign breast disease. Cell biology international, 30, 376-380.
GRYGLEWSKI, R., PALMER, R. & MONCADA, S. 1986. Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor. Nature, 320, 454-456.
HAMADAMIN, P., SALIHI, A., ABDOULRAHMAN, K., ALI QADIR, F., KHASRO, R., NAJDAT, J., HAMAD, N. & NAJMADDIN, H. 2016. Screening of Oxidative Stress and Prostate Cancer Biomarkers among Rural and Urban Elderly People in Erbil Governorate-Kurdistan Region. ZANCO Journal of Pure and Applied Sciences, 28, 202-208.
HARRIS, C. C. 1989. Interindividual variation among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis, 10, 1563-1566.
HIMMELFARB, J. 2005. Relevance of oxidative pathways in the pathophysiology of chronic kidney disease. Cardiology clinics, 23, 319-330.
KAHAN, E., IBRAHIM, A. S., NAJJAR, K. E., RON, E., AL-AGHA, H., POLLIACK, A. & EL-BOLKAINY, M. N. 1997. Cancer patterns in the Middle East special report from the Middle East Cancer Society. Acta oncologica, 36, 631-636.
KANG, D.-H. 2002. Oxidative stress, DNA damage, and breast cancer. AACN Advanced Critical Care, 13, 540-549.
KARAA, S., ZHANG, J. & YANG, F. 2005. A numerical study of a 3D bioheat transfer problem with different spatial heating. Mathematics and Computers in Simulation, 68, 375-388.
KESHAVIAH, A., DELLAPASQUA, S., ROTMENSZ, N., LINDTNER, J., CRIVELLARI, D., COLLINS, J., COLLEONI, M., THURLIMANN, B., MENDIOLA, C. & AEBI, S. 2007. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Annals of oncology, 18, 701-708.
KULIE, T., SLATTENGREN, A., REDMER, J., COUNTS, H., EGLASH, A. & SCHRAGER, S. 2011. Obesity and women's health: an evidence-based review. The Journal of the American Board of Family Medicine, 24, 75-85.
LI, A. N., LI, S., ZHANG, Y. J., XU, X. R., CHEN, Y. M. & LI, H. B. 2014. Resources and biological activities of natural polyphenols. Nutrients, 6, 6020-47.
MONTENARH, M. 1992. Biochemical properties of the growth suppressor/oncoprotein p53. Oncogene, 7, 1673-1680.
MUNZEL, T., SAYEGH, H., FREEMAN, B. A., TARPEY, M. M. & HARRISON, D. G. 1995. Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross-tolerance. The Journal of clinical investigation, 95, 187-194.
O'HARA, P. J., SHEPPARD, P. O., THóGERSEN, H., VENEZIA, D., HALDEMAN, B. A., MCGRANE, V., HOUAMED, K. M., THOMSEN, C., GILBERT, T. L. & MULVIHILL, E. R. 1993. The ligand-binding domain in metabotropic glutamate receptors is related to bacterial periplasmic binding proteins. Neuron, 11, 41-52.
ORGANIZATION, W. H. 1998. Quality control methods for medicinal plant materials, World Health Organization.
OSTROWSKI, J., SAWAN, A., HENRY, L., WRIGHT, C., HENRY, J., HENNESSY, C., LENNARD, T., ANGUS, B. & HORNE, C. 1991. p53 expression in human breast cancer related to survival and prognostic factors: an immunohistochemical study. The Journal of pathology, 164, 75-81.
PALMA, H. E., WOLKMER, P., GALLIO, M., CORREA, M. M., SCHMATZ, R., THOME, G. R., PEREIRA, L. B., CASTRO, V. S., PEREIRA, A. B., BUENO, A., DE OLIVEIRA, L. S., ROSOLEN, D., MANN, T. R., DE CECCO, B. S., GRACA, D. L., LOPES, S. T. & MAZZANTI, C. M. 2014. Oxidative stress parameters in blood, liver, and kidney of diabetic rats treated with curcumin and/or insulin. Mol Cell Biochem, 386, 199-210.
PAOLETTI, E., BELLINO, D., CASSOTTANA, P., ROLLA, D. & CANNELLA, G. 2005. Left ventricular hypertrophy in nondiabetic predialysis CKD. American journal of kidney diseases, 46, 320-327.
SARAN, M., MICHEL, C., BORS, W. & CZAPSKI, G. 1990. Reaction of NO with O2−. Implications for the action of endothelium-derived relaxing factor (EDRF). Free radical research communications, 10, 221-226.
SHANG, W., HUANG, L., LI, L., LI, X., ZENG, R., GE, S. & XU, G. 2016. Cancer risk in patients receiving renal replacement therapy: a meta-analysis of cohort studies. Molecular and clinical oncology, 5, 315-325.
SINGAL, A. K., JAMPANA, S. C. & WEINMAN, S. A. 2011. Antioxidants as therapeutic agents for liver disease. Liver Int, 31, 1432-48.
STOPPER, H., SCHUPP, N., BAHNER, U., SEBEKOVA, K., KLASSEN, A. & HEIDLAND, A. Genomic damage in end-stage renal failure: potential involvement of advanced glycation end products and carbonyl stress. Seminars in nephrology, 2004. Elsevier, 474-478.
TBAHRITI, H. F., KADDOUS, A., BOUCHENAK, M. & MEKKI, K. 2013. Effect of different stages of chronic kidney disease and renal replacement therapies on oxidant-antioxidant balance in uremic patients. Biochemistry research international, 2013.
THANNICKAL, V. J. & FANBURG, B. L. 2000. Reactive oxygen species in cell signaling. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279, L1005-L1028.
VALENTE, M. J., CARVALHO, F., BASTOS, M., DE PINHO, P. G. & CARVALHO, M. 2012. Contribution of oxidative metabolism to cocaine-induced liver and kidney damage. Curr Med Chem, 19, 5601-6.
WEISS, R. B. The anthracyclines: will we ever find a better doxorubicin? Seminars in oncology, 1992. 670-686.
WESSELING, C., ANTICH, D., HOGSTEDT, C., RODRíGUEZ, A. C. & AHLBOM, A. 1999. Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. International journal of Epidemiology, 28, 365-374.
YEH, C.-C., HOU, M.-F., TSAI, S.-M., LIN, S.-K., HSIAO, J.-K., HUANG, J.-C., WANG, L.-H., WU, S.-H., HOU, L. A. & MA, H. 2005. Superoxide anion radical, lipid peroxides and antioxidant status in the blood of patients with breast cancer. Clinica chimica acta, 361, 104-111.
How to Cite
Ahmad, A. and Abdoulrahman, K. (2020) “the Effect of oxidative stress on tumor suppressor protein p53 and some biochemical markers in breast cancer patients in Erbil governorate”, Zanco Journal of Pure and Applied Sciences, 32(6), pp. 60-71. doi: 10.21271/ZJPAS.32.6.7.
Biology and Medical Researches