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  • Title: Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer: the Rotterdam Study.
    Author: van der Knaap R, Siemes C, Coebergh JW, van Duijn CM, Hofman A, Stricker BH.
    Journal: Cancer; 2008 Feb 15; 112(4):748-57. PubMed ID: 18181094.
    Abstract:
    BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Renin-angiotensin system-inhibiting drugs seemed to protect against cancer in individuals with the DD genotype, which was associated with high levels of ACE.
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