Abstract 2598: An association study between AGTR2 and MAS1 gene polymorphisms with breast cancer among Brazilian women

Abstract

Background: Many different types of cancer (renal, lung, colorectal, prostate, uterus, breast and pancreatic) have already been associated to polymorphisms of the Renin Angiotensin System (RAS) genes. Angiotensin II (Ang II) is a vasoconstrictor, a mitogen and a angiogenic factor, whereas the angiotensin-(1-7) [Ang-(1-7)] has vasodilator, antiproliferative and anti-angiogenic properties. Classically, Ang II and Ang-(1-7) exert their effects through the AGTR 1-2 and the MAS1 oncogene receptors respectively. The MAS1 receptor expression is associated to lung cancer and the hormone Ang-(1-7) inhibits proliferation in these neoplasias. Moreover, some studies have correlated the MAS1 receptor gene expression to breast cancer. To further test the hypothesis that Ang II and Ang-(1-7) participate in breast carcinogenesis through AGTR2 and MAS1 oncogene receptors respectivelly, we assessed genetic polymorphisms in the 5′-region of the AGTR2 gene (T1247G and A5235G) and in the MAS1 oncogene (C647T) in two groups: breast cancer patients and normal women and their possible associations to breast cancer among Brazilian women. Methods: The genotyping assay was performed through the Custom TaqMan SNP Genotyping assays, probes and primers Assay-by-Design were used for the end-point collection qPCR human SNPs genotyping. Genomic DNA samples were extracted from blood cells of patients with (case) or without breast cancer (control), aged between 26 and 90 years. In the polymorphism T1247G, 428 samples were processed: 263 cases and 165 controls; 429 samples for polymorphism A5235G: 257 cases and 172 controls and 429 samples in polymorphism C647T: 269 cases and 167 controls. Results: The following distribution of genotypes (%)were obtained for the three polymorphisms: T1247G - TT, TG, GG = 84, 13, 03 in case and 81, 18, 1 in control (p = 0,0025); A5235G - AA, AG, GG = 21, 44, 35 in case and 20, 27, 35 in control (p = 0,36); C647T - CC, CT, TT = 64.0, 0.4, 35.6 in case and 52.0, 0.6, 47.4 in control (p = 0,039). Therefore, T1247G and C647T polymorphisms are associated with breast cancer. Conclusions: Our results suggest an association between T1247G AGTR2 and C647T MAS1 oncogene polymorphisms with breast cancer in the Brazilian population. Both polymorphisms are found in the promoter region of these genes, making of these regions possible targets to change the binding of transcription factors that will eventually transcribe these genes and might result in a different cellular behavior when exposed to the same agonist molecule. This being the case, the T1247G and C647T are possible targets for assessing breast cancer risk, while the A5235G is not. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2598. doi:1538-7445.AM2012-2598