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Plasma Levels of Angiotensin-Converting Enzymes 1 and 2 and AGTR2 (T1247G and A5235G) Gene Polymorphisms Are Associated to Breast Cancer Progression

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DOI: 10.4236/jct.2013.49167    4,110 Downloads   6,118 Views   Citations


Background: Breast cancer is the most common type of cancer among women. Diagnosed and treated timely, patients may have good prognostics. In Brazil, in 2012, the estimate of new cases was 52,680 and the number of registered deaths in 2012 was 12,852. The Renin-Angiotensin System (RAS) is known for its role in arterial hypertension and in other cardiovascular diseases. Angiotensin-Converting Enzyme 2 (ACE2) is the key to Ang-(1-7) formation, and counterbalances the ACE1/AngII/AGTR1 axis actions. RAS components have complex interactions with different tissues and their actions are not restricted to the cardiovascular system. Recently, the RAS has been associated with different types of cancers and in particular with gynecological cancers. Objectives: Our aim is to investigate possible associations between allelic distribution of two genetic polymorphisms in the AGTR2 receptor with ACEs 1 and 2 plasma levels among women with breast cancer. Patients and Methods: Patients with breast cancer were genotyped for two polymorphisms of the AGTR2 (T1247G and A5235G). Genotyping assays (TaqMan) were performed with genomic DNA extracted from blood cells. ACEs plasma level measurements were conducted in women from the breast-cancer group (N = 53). ACEs were measured in the plasma of these patients using ELISA kits. Results: SNPs genotype distribution is correlated with ACEs plasma levels. ACEs plasma levels are also correlated with clinical variables and ACE2 high levels are associated with better prognostics. Conclusions: Changes in circulating levels of ECA1/AngII ECA2/ Ang-(1-7) determine the magnitude of the inflammatory response that an individual can trigger and the variation in ACE 1 and 2 plasma level measurements in the blood of breast cancer patients suggests an association with the process of mammary carcinogenesis. Thus, the RAS may be associated with the process of mammary carcinogenesis by both genotypic variations of RAS components and by circulating levels of ACEs.

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The authors declare no conflicts of interest.

Cite this paper

M. Wolgien, I. Silva, A. Nazário, C. Nakaie, S. Noronha, S. Noronha and G. Facina, "Plasma Levels of Angiotensin-Converting Enzymes 1 and 2 and AGTR2 (T1247G and A5235G) Gene Polymorphisms Are Associated to Breast Cancer Progression," Journal of Cancer Therapy, Vol. 4 No. 9, 2013, pp. 1403-1410. doi: 10.4236/jct.2013.49167.


[1] J. S. Berek, “Berek & Novak’s Gynecology,” 14th Edition, Wolters Kluwer Health/Lippincott Williams & Wilkins, Philadelphia, 2011, p. 1539.
[2] M. Smalley and A. Ashworth, “Stem Cells and Breast Cancer: A Field in Transit,” Nature Reviews Cancer, Vol. 3, No. 11, 2003, pp. 832-844.
[3] A. Jemal, R. Siegel, J. Xu and E. Ward, “CA Cancer,” Journal of Clinical, Vol. 60, No. 5, 2010, pp. 277-300.
[4] A. Ribeiro-Oliveira Jr., A. I. Nogueira, R. M. Pereira, W. W. Boas, R. A. Dos Santos and A. C. Simoes e Silva, “The Renin-Angiotensin System and Diabetes: An Update,” Journal of Vascular Health and Risk Management, Vol. 4, No. 4, 2008, pp. 787-803.
[5] T. P. Wong, K. Y. Ho, E. K. Ng, E. S. Debnam and P. S. Leung, “Upregulation of ACE2-ANG-(1-7)-Mas Axis in Jejunal Enterocytes of Type 1 Diabetic Rats: Implications for Glucose Transport,” American Journal of Physiology, Endocrinology and Metabolism, Vol. 303, No. 5, 2012, pp. E669-E681.
[6] G. Li, N. Xi and D. H. Wang, “Investigation of Angiotensin II Type 1 Receptor by Atomic Force Microscopy with Functionalized Tip,” Nanomedicine, Vol. 1, No. 4, 2005, pp. 306-312.
[7] S. Arumugam, R. A. Thandavarayan, S. S. Palaniyandi, et al., “Candesartan Cilexetil Protects from Cardiac Myosin Induced Cardiotoxicity via Reduction of Endoplasmic Reticulum Stress and Apoptosis in Rats: Involvement of ACE2-Ang(1-7)-Mas Axis,” Toxicology, Vol. 291, No. 1-3, 2012, pp. 139-145.
[8] M. Tahmasebi, J. R. Puddefoot, E. R. Inwang and G. P. Vinson, “The Tissue Reninangiotensin System in Human Pancreas,” Journal of Endocrinology, Vol. 161, No. 2, 1999, pp. 317-322.
[9] D. G. Passos-Silva, T. Verano-Braga and R. A. Santos, “Angiotensin-(1-7): Beyond the Cardio-Renal Actions,” Clinical Science, Vol. 124, No. 7, 2013, pp. 443-456.
[10] U. N. Das, “Angiotensin-II Behaves as an Endogenous Pro-Inflammatory Molecule,” Journal of Association of Physicians of India, Vol. 53, 2005, pp. 472-476.
[11] Y. R. Qian, Y. Guo, H. Y. Wan, L. Fan, Y. Feng, L. Ni, Y. Xiang and Q. Y. Li, “Angiotensin-Converting Enzyme 2 Attenuates the Metastasis of Non-Small Cell Lung Cancer through Inhibition of Epithelial-Mesenchymal Transition,” Oncology Reports, Vol. 29, No. 6, 2003, pp. 2408-2414.
[12] J. R. Puddefoot, U. D. K. Udeozo, S. Barker and G. P. Vinson, “The Role of Angiotensin II in the Regulation of Breast Cancer Cell Adhesion and Invasion,” Endocrine-Related Cancer, Vol. 13, No. 3, 2006, pp. 895-903.
[13] P. E. Gallagher, K. Cook, D. Soto-Pantoja, J. Menon and E. A. Tallant, “Angiotensin Peptides and Lung Cancer,” Current Cancer Drug Targets, Vol. 11, No. 4, 2011, 2011, pp. 394-404.
[14] Y. Feng, H. Wan, J. Liu, et al., “The Angiotensin-Converting Enzyme 2 in Tumor Growth and Tumor-Associated Angiogenesis in Non-Small Cell Lung Cancer,” Oncology Reports, Vol. 23, No. 4, 2010, pp. 941-948.
[15] S. A. A. C. Noronha, W. Bernardo, A. J. Barros, C. R. Nakaie, S. I. Shimuta, I. D. C. G. Silva and S. M. R. Noronha, “Effects on Cell Viability and on Apoptosis in Tumoral (MCF-7) and in Normal (MCF10A) Epithelial Breast Cells after Human Chorionic Gonadotropin and Derivated-Angiotensin Peptides Treatments,” Journal of Cancer Therapy, Vol. 4, No. 7, 2013, pp. 65-69.
[16] I. Binda Neto, S. M. R. Noronha, S. A. A. C. Noronha, M. D. C. M. Wolgien, A. J. Barros, C. R. Nakaie, S. I. Shimuta, G. Facina and I. D. C. G. Silva, “Angiotensin-(1-7) and Human Chorionic Gonadotropin (hCG) Modulate the Nuclear Transcription Factors or Nuclear Receptors Genes in the Tumorigenic Undifferentiated Breast Cancer Cell Line SKBR3,” Journal of Cancer Therapy, Vol. 4, No. 7A, 2013, pp. 70-74.
[17] S. A. A. Corrêa, S. M. R. Noronha, N. C. Nogueira-deSouza, C. V. V. Carvalho, A. M. M. Costa, J. J. Linhares, M. T. V. Gomes and I. D. G. Silva, “Association between the Angiotensin-Converting Enzyme (Insertion/Deletion) and Angiotensin II Type 1 Receptor (A1166C) Polymorphisms and Breast Cancer among Brazilian Women,” Journal of Renin Angiotensin Aldosterone System, Vol. 10, No. 1, 2009, pp. 51-58.
[18] S. A. Correa-Noronha, S. A. Ribeiro de Noronha, C. Alecrim, A. D. Mesquita, G. S. Brito, M. G. Junqueira, D. B. Leite, C. V. Carvalho and I. D. Silva, “Association of Angiotensin-Converting Enzyme I Gene I/D Polymorphism with Endometrial but Not with Ovarian Cancer,” Gynecology Endocrinology, Vol. 28, No. 11, 2012, pp. 889-891.

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