Angiotensin-converting enzyme gene insertion/deletion polymorphism and breast cancer risk

Erasmus Universiteit Rotterdam, Rotterdam, South Holland, Netherlands
Cancer Epidemiology Biomarkers & Prevention (Impact Factor: 4.13). 10/2005; 14(9):2143-6. DOI: 10.1158/1055-9965.EPI-05-0045
Source: PubMed


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.

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    • "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 "
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    • "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 [43]. 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. "
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    • "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. "
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