RAS polymorphisms in cancerous and benign breast tissue (original) (raw)
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Journal of Cancer Therapy, 2013
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.
Background: Breast cancer is the most common type of cancer among women. Many types of cancer are associated with polymorphisms of the renin-angiotensin system (RAS). Angiotensin II (Ang II) is a vasoconstrictor, a mitogen and an angiogenic factor. Ang II exerts its effect through two receptors (AGTR 1-2). T1247G and A5235G are two SNPs within the 5′-region of the AGTR2 gene. Objectives: Our aim was to investigate the association between (T1247G and A5235G) SNPs with breast cancer among Egyptian females. Patients and Methods: One hundred Egyptian women were included in the present study; 50 cases and 50 controls. Data about age, menstrual and family history were obtained. TNM category and axially LN status were also assessed in breast cancer patients. All subjects were genotyped for AGTR2 (T1247G and A5235G) SNPs using the Custom TaqMan SNP Genotyping assays. Results: For A5235G, women carrying genotypes AA/AG were more likely to develop breast cancer than GG carriers (OR = 4.125, 95% CI: 1.473-11.555). A significant association was observed between (A5235G) genotypes and both TNM category and axillary LN. Also, a significant association between (T1247G) genotypes and TNM category with the mutant GG genotype being predictor of poor outcome. Multivariate logistic regression analysis proved that (A5235G) SNP genotypes significantly contribute to the prediction of breast cancer risk. Conclusions: Our study suggests that RAS is implicated in the development and in the invasion of breast cancer.
Dr Genetic Association of Angiotensin Converting Enzyme I/D Gene Polymorphisms with Breast Cancer
European Journal of Biology and Biotechnology
Breast cancer presents a serious public health risk in both developed and developing countries. The ACE gene, which is located in chromosome 17q23, has many polymorphisms. The most commonly studied is a 287 bp Alu insertion/deletion (I/D) polymorphism in intron 16 that accounts for 50% of the variability in circulating ACE levels. The main aim of this study is to find out the association of ACE gene with breast cancer in Pakistani population. Experimental and cross-sectional. A total of 186 samples were collected. Of the 186, 93 were taken as healthy controls and 93 were the female patients suffering from breast cancer. First DNA was isolated and then further genotypes II, ID and DD were identified by Nested PCR. Chi-square (χ2) test was applied to check the association level between ACE I/D polymorphism and breast cancer. The DD genotype showed (76) 81.7% and ID showed (17) 18.2% whereas II was not found (0) 0% in breast cancer patients. In controls, the frequency of DD is (80) 86%...
Genetic Association of Angiotensin Converting Enzyme I/D Gene Polymorphisms with Breast Cancer
European Journal of Biology and Biotechnology, 2020
Breast cancer presents a serious public health risk in both developed and developing countries. The ACE gene, which is located in chromosome 17q23, has many polymorphisms. The most commonly studied is a 287 bp Alu insertion/deletion (I/D) polymorphism in intron 16 that accounts for 50% of the variability in circulating ACE levels. The main aim of this study is to find out the association of ACE gene with breast cancer in Pakistani population. Experimental and cross-sectional. A total of 186 samples were collected. Of the 186, 93 were taken as healthy controls and 93 were the female patients suffering from breast cancer. First DNA was isolated and then further genotypes II, ID and DD were identified by Nested PCR. Chi-square (χ2) test was applied to check the association level between ACE I/D polymorphism and breast cancer. The DD genotype showed (76) 81.7% and ID showed (17) 18.2% whereas II was not found (0) 0% in breast cancer patients. In controls, the frequency of DD is (80) 86%...
Journal of The Renin-angiotensin-aldosterone System, 2009
Introduction. We evaluated the association between components of the renin-angiotensin system and the development of breast cancer in a case-control study by means of angiotensinconverting enzyme (ACE) insertion/deletion (I/D) and angiotensin II type 1 (AT 1 )-receptor A1166C polymorphisms. Methods. Genotyping was performed by PCR-RFLP (restriction fragment length polymorphism) or PCR (polymerase chain reaction) using genomic DNA extracted from buccal cells of subjects with (101 cases) or without (307 controls) breast cancer. Results. The frequencies of genotypes for ACE were: DD, ID and II (in %: cases: 60; 20; 20; controls: 46; 37; 17; p=0.019, χ 2 ); and for AT 1receptor were: AA, AC and CC (in %: cases: 65; 30; 5; controls: 51; 44; 5; p=0.114, χ 2 ). The results suggested that the A1166C polymorphism was not associated with breast cancer risk. On the other hand, for the ACE (I/D), there seemed to be different risks for cancer between cases and controls. Conclusions. The ID genotype was less frequently associated with the disease than were the DD or II; that is, women with the ID genotype were 3.1 times less likely to develop breast cancer than those with the other genotypes. The ID genotype might be protective against breast cancer and the ACE (I/D) polymorphism a possible target for developing genetic markers for breast cancer.
The Tohoku Journal of Experimental Medicine, 2006
The association between the polymorphism of the angiotensin-converting enzyme (ACE) gene and breast cancer risk has been extensively studied, however, the studies about the prognostic factors and ACE gene polymorphism are limited in number. Our aims were to analyze the distribution of the insertion/deletion (I/D) polymorphism of the ACE gene in Turkish premenopausal patients with breast cancer, which is more aggressive than the postmenopausal counterpart, and to assess whether DD genotype is associated with poor prognostic factors. The DD genotype has been shown to be associated with the increased serum and tissue levels of ACE, compared to those in II and ID genotypes. ACE genotypes were determined by polymerase chain reaction in 44 Turkish premenopausal patients with breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes are distributed in patients and control subjects as follows; DD is present in 25 (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in healthy subjects, respectively. In breast cancer patients, no significant association was observed between the ACE genotypes and poor prognostic factors, such as negative hormone receptor status, histological grade, lymph node involvement, higher number of lymph node metastases, and c-erb B2 overexpression, except that tumor size greater than 2 cm is associated with DD genotype (p = 0.02). Thus, ACE may influence the local tumor growth of breast cancer in premenopausal patients.
Journal of Investigative Medicine, 2007
The aims of the present study were to investigate the distribution of the insertion/deletion (I/D) polymorphism of the angiotensin-converting enzyme (ACE) gene in breast cancer patients and the association between ACE genotypes and clinicopathologic features, as well as their effects on prognosis. We assessed the I/D polymophism of the ACE gene by using polymerase chain reaction from peripheral blood in breast cancer and healthy age-matched women. The clinicopathologic parameters of breast cancer patients were obtained from medical records. Of the 57 patients, 31 (54.4%) had DD, 24 (42.1%) had ID, and 2 (3.5%) had II genotypes. In control subjects, 33 (63.5%) had DD, 12 (23.1%) had ID, and 7 (13.4%) had II genotypes. The ID genotype was seen more commonly in breast cancer patients (p = .03). When the combination of ID and II genotypes was used as a reference group, the DD genotype was associated with negative hormone receptor status (p = .003), tumor size (p = .054), and lymph node involvement (p = .07) but not histologic high grade and c-erb B2 overexpression. These results suggest that the DD genotype may accompany poor prognostic factors and influence the tumor course.
Asian Journal of Biochemistry, Genetics and Molecular Biology, 2022
Background: According to GLOBOCAN estimates, breast cancer was found to be the most often diagnosed cancer in women worldwide, (11.7 %) and the fourth leading cause of cancer mortality (6.9 %). Aim: The purpose of this study is to investigate the role of the Angiotensin I-converting enzyme (ACE) gene polymorphism in breast cancer prediction risk in Egyptian population. Methods: Polymorphism detection analysis was performed on 163 subjects from breast cancer (BC) patients, 79 with Benign Breast Disease group (BBD) patients and 202 controls (C). ACE I/D (rs1799752) polymorphism were detected using polymerase chain reaction (PCR). Results: The observed genotype frequencies were II 10.9%, ID 78.2% and DD 10.9% in healthy control, II 8.6%, ID 79.1% and DD 12.3% in BC patients and II 12.6%, ID 78.4% and DD 9% in BBD patients. There were no association between ACE gene polymorphisms, between the BC or BBD groups when compared to the control group (ORDD= 1.43, 95 % CI= (0.58-3.52), P= 0.29)...
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The association between the polymorphism of the angiotensinconverting enzyme (ACE) gene and breast cancer risk has been extensively studied, however, the studies about the prognostic factors and ACE gene polymorphism are limited in number. Our aims were to analyze the distribution of the insertion/deletion (I/D) polymorphism of the ACE gene in Turkish premenopausal patients with breast cancer, which is more aggressive than the postmenopausal counterpart, and to assess whether DD genotype is associated with poor prognostic factors. The DD genotype has been shown to be associated with the increased serum and tissue levels of ACE, compared to those in II and ID genotypes. ACE genotypes were determined by polymerase chain reaction in 44 Turkish premenopausal patients with breast cancer and in 46 age-matched healthy premenopausal women. ACE genotypes are distributed in patients and control subjects as follows; DD is present in 25 (56.8%), ID in 17 (38.6%), and II in 2 (4.5%) patients, and DD in 28 (60.9%), ID in 12 (26.1%), and II in 6 (13.0%) healthy subjects, respectively. D and I alleles were found in 76.1% and 23.9% of the patients, while 73.9% and 26.1% in healthy subjects, respectively. In breast cancer patients, no significant association was observed between the ACE genotypes and poor prognostic factors, such as negative hormone receptor status, histological grade, lymph node involvement, higher number of lymph node metastases, and c-erb B2 overexpression, except that tumor size greater than 2 cm is associated with DD genotype (p = 0.02). Thus, ACE may influence the local tumor growth of breast cancer in premenopausal patients. premenopause breast cancer; ACE gene polymorphism; poor prognostic factors