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Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer
The Rotterdam Study
Version of Record online: 7 JAN 2008
Copyright © 2008 American Cancer Society
Volume 112, Issue 4, pages 748–757, 15 February 2008
How to Cite
van der Knaap, R., Siemes, C., Coebergh, J.-W. W., van Duijn, C. M., Hofman, A. and Stricker, B. H. Ch. (2008), Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer. Cancer, 112: 748–757. doi: 10.1002/cncr.23215
- Issue online: 1 FEB 2008
- Version of Record online: 7 JAN 2008
- Manuscript Accepted: 31 AUG 2007
- Manuscript Revised: 22 AUG 2007
- Manuscript Received: 28 JUN 2007
- angiotensin II;
- angiotensin I-converting enzyme inhibitor;
- prospective cohort study
Angiotensin I-converting enzyme (ACE) inhibitors, angiotensin II antagonists, and the ACE insertion/deletion (I/D) gene polymorphism all influence serum angiotensin II action. Because angiotensin II levels have been associated with cancer, the objective of the current epidemiologic study was to investigate whether renin-angiotensin system inhibitors and/or ACE genotypes were associated with an altered risk of colorectal, lung, breast, and prostate cancer.
Data were obtained from the Rotterdam Study, a population-based, prospective cohort study with 7983 participants. Participants who had a history of 1 of the cancers of interest (n = 216) or who had a medication history <6 months (n = 88) were excluded, leaving 7679 participants, of whom the ACE genotypes could be assessed in 6670 individuals. The mean follow-up was 9.6 years, during which 730 incident cancers occurred. The effect of medication, ACE I/D genotypes, and their interaction on cancer risk and progression was studied by using Cox proportional hazard models.
Carriers of the high-activity genotype DD had an increased risk of breast cancer compared with low-activity II/ID genotype carriers (hazard ratio [HR], 1.47; 95% confidence interval [95% CI], 1.05–2.04), but no association was demonstrated for other cancers. DD carriers who were exposed to long-term and high-dose medication were at lower risk for cancer (HR, 0.28; 95% CI, 0.10–0.79). Short-term, high-dose users were at risk for colorectal cancer progression in the II/ID stratum (HR, 3.83; 95% CI, 1.67–8.79).
Renin-angiotensin system-inhibiting drugs seemed to protect against cancer in individuals with the DD genotype, which was associated with high levels of ACE. Cancer 2008. © 2008 American Cancer Society.