The renin-angiotensin system plays an important role in homeostasis and lately, its main effector, angiotensin II, has been attributed with angiogenic and growth factor actions in the breast tissue. Previous studies have shown that the insertion/deletion (I/D) polymorphism in the angiotensin-converting enzyme (ACE) gene accounts for the variability of ACE plasma concentrations. The use of ACE inhibitors and the ACE I/D polymorphism may be linked to breast cancer risk. In this study, we evaluate the relationship of the ACE I/D polymorphism with breast cancer risk in Caucasian postmenopausal women.
The ACE I/D polymorphism was genotyped in 4,117 women participants in the Rotterdam Study. Baseline information was obtained through a questionnaire. We conducted a logistic regression and survival analysis to assess the risk of breast cancer by the ACE genotype.
The DD carriers showed a significantly increased risk of developing breast cancer when compared with the II carriers (odds ratio, 1.86; 95% confidence interval, 1.06-3.27; P = 0.03). This association remained after adjusting for other risk factors, including body mass index, age at menarche, age at menopause, hormone replacement therapy, and hypertension. Our survival analysis showed that the cancer-free survival was significantly reduced in DD compared with II carriers (hazard ratio, 1.80; 95% confidence interval, 1.07-3.01; P = 0.03).
Our results suggest that the ACE I/D polymorphism plays an important role in breast cancer risk and disease-free survival in Caucasian postmenopausal women.
"The ACE I/D polymorphism has been identified as a possible target for developing genetic markers for breast cancer in Brazilian women.63 The ACE I/D polymorphisms were shown to play an important role in breast cancer risk and disease-free survival in Caucasian postmenopausal women.64 Carriers of the high-activity DD genotype exhibited an increased risk of breast cancer compared with low activity II/ID genotype carriers.65 "
[Show abstract][Hide abstract] ABSTRACT: Cancer is the leading cause of death in the USA, and the incidence of cancer increases dramatically with age. Beta-adrenergic blockers appear to have a beneficial clinical effect in cancer patients. In this paper, we review the evidence of an association between β-adrenergic blockade and cancer. Genetic studies have provided the opportunity to determine which proteins link β-adrenergic blockade to cancer pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin-angiotensin system, transcription factor nuclear factor-kappa-light-chain-enhancer of activated B cells, poly(ADP-ribose) polymerase-1, vascular endothelial growth factor, and the reduced form of nicotinamide adenine dinucleotide phosphate oxidase. Beta-adrenergic blockers also exert anticancer effects through non-genomic factors, including matrix metalloproteinase, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, β-adrenergic blockade may play a beneficial role in cancer treatment. Additional investigations that examine β-adrenergic blockers as cancer therapeutics are required to further elucidate this role.
Cancer Management and Research 12/2012; 4:431-45. DOI:10.2147/CMAR.S39153
"Aside from our results, such a conclusion stems also from recent reports suggesting significant effects of an imbalance between activities of angiotensin-converting enzymes (ACE and ACE2) in the development of breast cancer . This hypothesis was confirmed by studies demonstrating a marked increase in incidence of breast cancer in women carrying D/D allele of the ACE gene, which is linked to higher levels of the circulating ACE isoform in blood of these patients [44, 45]. In addition, our results have confirmed effect of AT-1R on expression of VEGF-A. "
[Show abstract][Hide abstract] ABSTRACT: Recent studies point to the involvement of angiotensin II (Ang II) receptor type 1 (AT-1R) on processes of metastasing, stimulation of invasiveness and angiogenesis in tumours. In this study, the correlation between intensity of AT-1R expression and expression of lymph- and angiogenesis markers in invasive ductal breast cancers (IDC) was examined. Immunohistochemical studies (IHC) were performed on archival material of 102 IDC cases. Only 28 (27.5%) cases manifested low AT-1R expression while 74 (72.5%) cases demonstrated a moderate or pronounced AT-1R expression. Expression intensity of AT-1R was found to correlate with expressions of VEGF-A (r = 0.26; p = 0.008) and VEGF-D (r = 0.24; p = 0.015). Out of the examined markers of angiogenesis and lymphangiogenesis only the pronounced expression of VEGF-C was found to correlate with patient poor clinical outcome (p = 0.009). The positive correlation between AT-1R and VEGF-A and VEGF-D could point to stimulatory action of Ang II on their expression what might result in augmented lymph- and angiogenesis in IDC.
"Survival analysis performed by Kaplan- Meier method in our study showed that the disease free survival was reduced in DD genotype or D allele compared with ID/II genotype or I allele. It was reported that cancer-free survival was significantly reduced in patients with DD genotype compared with II genotype in a breast cancer study (Ladd et al. 2005). In the other studies with prostate cancer (Medeiros et al. 2004) and leukemia patients (Hajek et al. 2003), decreased survival time was also reported in patients who had DD genotype. "
[Show abstract][Hide abstract] ABSTRACT: 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.
The Tohoku Journal of Experimental Medicine 11/2006; 210(2):109-16. DOI:10.1620/tjem.210.109 · 1.35 Impact Factor
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