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Differential Roles of Angiotensinogen and Angiotensin Receptor type 1 Polymorphisms in Breast Cancer Risk

  • Epidemiology
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Abstract

While angiotensinogen (AGT) seems to have anti proliferative properties, angiotensin II (ATII) is a potent growth factor and it mediates its actions through the angiotensin type 1 receptor (AGTR1). In the AGT gene, the M235T polymorphism has been associated with the variation in angiotensinogen levels and in the AGTR1 gene; the C573T variant is associated with different pathologies. We aimed to evaluate the relationship of these two variants and the risk of breast cancer. These polymorphisms were genotyped in 3787 women participating the Rotterdam Study. We performed a logistic regression and a disease free survival analysis by genotype. The logistic regression yielded an odds ratio of 1.4 (95% CI: 1.1–1.9) for the MM genotype carriers versus the T allele carriers. The breast cancer free survival by AGT genotype was significantly reduced in MM genotype carriers compared to non-carriers (hazard ratio (HR) = 1.5; 95% CI: 1.1–2.2). We did not find any association of the AGTR1 polymorphism and breast cancer risk or disease free survival. Our results suggest that AGT plays a role in breast cancer risk in postmenopausal women, whereas the role of AGTR1 needs further studying.

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Acknowledgments

A. Arias Vasquez is supported by a grant from the Centre of Medical Systems Biology, grant # 297–2003. The Rotterdam Study is supported by the Erasmus Medical Center and Erasmus University Rotterdam, the Netherlands Organization for Scientific Research (NWO), the Netherlands Organization for Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry of Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam.

These sponsors had no role in study design, data collection, data interpretation, or the writing of this report.

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Correspondence to C. M. van Duijn.

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Ladd, A.M.GZ., Vásquez, A.A., Siemes, C. et al. Differential Roles of Angiotensinogen and Angiotensin Receptor type 1 Polymorphisms in Breast Cancer Risk. Breast Cancer Res Treat 101, 299–304 (2007). https://doi.org/10.1007/s10549-006-9290-0

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