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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.

Original publication

DOI

10.1002/cncr.23215

Type

Journal article

Journal

Cancer

Publication Date

02/2008

Volume

112

Pages

748 - 757

Addresses

Department of Epidemiology and Biostatistics, Erasmus Medical Center, Rotterdam, Netherlands.

Keywords

Humans, Neoplasms, Breast Neoplasms, Colorectal Neoplasms, Lung Neoplasms, Prostatic Neoplasms, Peptidyl-Dipeptidase A, Angiotensin II Type 1 Receptor Blockers, Angiotensin-Converting Enzyme Inhibitors, Incidence, Proportional Hazards Models, Risk Assessment, Cohort Studies, Follow-Up Studies, Mutagenesis, Insertional, Sequence Deletion, Renin-Angiotensin System, Genotype, Polymorphism, Genetic, Aged, Aged, 80 and over, Middle Aged, Netherlands, Female, Male