Renin-angiotensin system inhibitors, angiotensin I-converting enzyme gene insertion/deletion polymorphism, and cancer : The Rotterdam Study

✍ Scribed by Ronald van der Knaap; Claire Siemes; Jan-Willem W. Coebergh; Cornelia M. van Duijn; Albert Hofman; Bruno H. Ch. Stricker

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 111 KB
• Volume: 112
• Category: Article
• ISSN: 0008-543X
• DOI: 10.1002/cncr.23215

✦ Synopsis

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. Cancer 2008. © 2008 American Cancer Society.