Association of ACE Inhibitors and Angiotensin Receptor Blockers with Keratinocyte Cancer Prevention in the Randomized VATTC Trial
Open Access
- 26 August 2008
- journal article
- research article
- Published by Oxford University Press (OUP) in JNCI Journal of the National Cancer Institute
- Vol. 100 (17), 1223-1232
- https://doi.org/10.1093/jnci/djn262
Abstract
Background The observation that angiotensin II is a potent angiogenic and growth factor raises the possibility that blocking its effects could reduce the incidence of cancer. We evaluated associations between use of angiotensin-converting enzyme (ACE) inhibitors and of angiotensin receptor blockers (ARBs) and keratinocyte cancer incidence in a population at high risk of the disease. Methods A cohort study design was conducted using data on 1051 participants in the randomized Department of Veterans Affairs Topical Tretinoin Chemoprevention (VATTC) Trial, all of whom were at increased risk of basal cell carcinoma (BCC) or squamous cell carcinoma (SCC). We followed participants from enrollment (November 1998 through January 2003) until first BCC or SCC. Study participants were examined every 6 months by a study dermatologist; biopsies were taken on all suspicious lesions and centrally reviewed. Use of ACE inhibitors and ARBs was ascertained from VA pharmacy records. Cox proportional hazards models were used to estimate adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) of BCC and SCC with use of ACE inhibitors or ARBs. Results During a median follow-up of 3.4 years, 472 incident BCCs, 309 SCCs, and 200 deaths from any cause were observed. Compared with nonusers, users of ACE inhibitors or ARBs had statistically significantly reduced risks of BCC (IRRBCC = 0.61, 95% CI = 0.50 to 0.76) and SCC (IRRSCC = 0.67, 95% CI = 0.52 to 0.87). The combined absolute incidence rates of BCC and SCC were 237 per 1000 person-years among users of ACE inhibitors or ARBs and 374 per 1000 person-years among nonusers. The greatest reduction in keratinocyte cancer was seen among people who initiated use of ACE inhibitors or ARBs during the study period (IRRBCC = 0.45 [95% CI = 0.34 to 0.59]; IRRSCC = 0.48 [95% CI = 0.35 to 0.67]). Conclusion Among a high-risk group of veterans, users of ACE inhibitors or ARBs had a lower incidence of keratinocyte cancers than nonusers. The more pronounced reduction among those who initiated use during the study may indicate an immediate effect.This publication has 28 references indexed in Scilit:
- Cancer Statistics, 2003CA: A Cancer Journal for Clinicians, 2003
- The Period Prevalence and Costs of Treating Nonmelanoma Skin Cancers in Patients Over 65 Years of Age Covered by MedicareDermatologic Surgery, 2001
- Angiotensin-converting enzyme inhibitors and the risk of cancerCancer, 2001
- Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?The Lancet, 1998
- Cancer statistics, 1998CA: A Cancer Journal for Clinicians, 1998
- Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats.JCI Insight, 1996
- The Role of Angiotensin II and Prostaglandins in Arcade Formation in a Developing Microvascular NetworkJournal of Vascular Research, 1996
- Angiotensin II stimulates angiogenesis in the chorio-allantoic membrane of the chick embryoEuropean Journal of Pharmacology, 1991
- Angiotensin-Converting Enzyme Inhibition Reduces Neuroblastoma Cell Growth RateExperimental Biology and Medicine, 1991
- Angiotensin II-induced proliferation of aortic myocytes in spontaneously hypertensive ratsJournal of Hypertension, 1990