Abstract 5592: Lack of association between AGTR1 (A168G and T825A) and ACE T5529C polymorphisms with breast cancer among Brazilian women

Abstract

Background: Angiotensin II (AngII) exerts promitotic, pro-proliferative and angiogenic effects and the administration of angiotensin I-converting enzyme (ACE) inhibitors reduces tumor growth in animal models of cancer. AngII type 1 receptor (AGTR1) is found in a wide variety of normal tissues, increased expression is often found in the corresponding neoplastic tissues, suggesting that its overexpression is involved in carcinogenesis. In a previous study we observed that the ID genotype might be protective against breast cancer and also that the ACE (I/D) polymorphism is a possible target for developing genetic markers for breast cancer. Other authors have also observed the association of the ACE with breast cancer risk. To further test the hypothesis that AngII participates in breast carcinogenesis through AGTR1 and ACE, we examined genetic polymorphisms in the 5’-region of the AGTR1 gene (A-168G and T-825A) and in the ACE (T5529C) in relation to risk of breast cancer among Brazilian women. Methods: Genotyping was performed through Real Time PCR (A168G and T825A) or PCR-RFLP (T5529C) using genomic DNA extracted from buccal cells of subjects with or without breast cancer.Results: Patients with (case) or without (control) breast cancer aging from 30 to 90 years old were genotyped for A168G (n=516), and the following frequencies obtained for AA, AG and GG in % were, among cases: 63, 30, 07 and among controls: 64, 32, 04 (p = 0.89). For T825A (n=562), we determined the frequency of TT, TA and AA (in %, cases: 62, 33, 05; controls: 59, 33, 08; p = 0.68). At last, for ACE (T5529C) (n=272) these are the obtained frequencies for TT, TC and CC genotypes in %, among cases: 65, 23, 12 and among controls: 55, 29, 15 (p = 0.39). Conclusion: Our results suggest a lack of significant association between AGTR1 polymorphisms (A168G and T825A) with breast cancer risk in the Brazilian population, in contrast to a previous result among Chinese women, where an association of the AGTR1 polymorphisms with breast cancer has been reported. Regarding the ACE T5529C polymorphism, it also did not show any association with breast cancer risk in the present study, differently from the observed for another polymorphism of the same gene, the ACE (I/D). Therefore, the AGTR1 (A168G and T825A) and ACE (T5529C) variant genotypes do not appear to be related to risk of breast cancer among Brazilian women. Support: FAPESP. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5592. doi:10.1158/1538-7445.AM2011-5592