Association of ACE inhibitors and angiotensin receptor blockers with keratinocyte cancer prevention in the randomized VATTC trial.
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 (IRR(BCC) = 0.61, 95% CI = 0.50 to 0.76) and SCC (IRR(SCC) = 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 (IRR(BCC) = 0.45 [95% CI = 0.34 to 0.59]; IRR(SCC) = 0.48 [95% CI = 0.35 to 0.67]).


CONCLUSIONS
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.
Christian
Jennifer B
JB
Department of Community Health, Brown University, Providence, RI 02912, USA. JChristian111@gmail.com
Lapane
Kate L
KL
Hume
Anne L
AL
Eaton
Charles B
CB
Weinstock
Martin A
MA
D000368:Aged; D000369:Aged, 80 and over; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D002280:Basal Cell Carcinoma / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D015603:Keratinocytes; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors; D012878:Skin Neoplasms / Q000175:diagnosis / Q000453:epidemiology* / Q000401:mortality / Q000517:prevention & control*
D047228:Angiotensin II Type 1 Receptor Blockers; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors