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ACE Inhibitors Associated With Reduced Risk of GI Tract Cancers

Thousands of individuals currently taking ACE inhibitors may not only be treating their hypertension but also reducing their risk of developing esophageal, pancreatic, and colon cancers, according to research presented at Digestive Disease Week 2006 (DDW) held May 20-25, 2006, in Los Angeles, California. DDW is the annual meeting jointly sponsored by the American Association for the Study of Liver Diseases, the American Gastroenterological Association, the American Society for Gastrointestinal Endoscopy, and the Society for Surgery of the Alimentary Tract.

Investigators led by Vikas Khurana, MD (Overton Brooks VA Medical Center, Shreveport, Louisiana) presented the results of 3 retrospective case-controlled studies that examined the correlation between ACE inhibitor use and the incidence of esophageal, pancreatic, and colon cancer in a study population of almost 500,000 US veterans.^[10-12]

Dr. Khurana and colleagues analyzed statistics from the Veterans' Integrated Service Network (VISN 16) database, a resource tool containing clinical and demographic information about all veterans (> 1.4 million patients) who received care from the South Central VA Health Care Network from October 1998 to June 2004. Among the 483,733 patients in the study, 659 (0.14%) had esophageal cancer, 475 (0.1%) had pancreatic cancer, and 6697 (1.4%) had colon and rectal cancer. A total of 185,830 (38.4%) patients were using ACE inhibitors. Evaluation of the use of ACE inhibitors prior to the cancer diagnosis revealed that ACE inhibitors were associated with a reduction in risk for all 3 cancer types. Use of ACE inhibitors was most effective in lowering the risk of developing esophageal cancer, with a 55% risk reduction compared with the controls (odds ratio [OR] 0.546; 95% CI 0.450-0.662, P < .01). The protective effect of ACE inhibitors was independent of statin use.

Results from the second study showed that ACE inhibitor use was associated with a 48% reduction in risk of pancreatic cancer (OR 0.484; 95% CI 0.386-0.607, P < .01). In the third study, the investigators found that ACE inhibitor use was associated with a 47% reduced risk of colon cancer (OR 0.47; 95% CI 0.45-0.50, P < .0001).

The studies were controlled for age, race, gender, body mass index, smoking, alcohol use, reflux, nonsteroidal anti-inflammatory use, diabetes, and statin use. However, dosage, duration, and type of ACE inhibitor used were not factored into the analyses. "Our results call for further studies to investigate the promising benefits of ACE inhibitors in cancer prevention," said Dr. Khurana. "Through confirmatory research we hope to shed light on the valuable role ACE inhibitors may play in advancing current treatment options for multiple cancers," he said.

Recent studies have revealed that the renin-angiotensin system is involved in the development of many types of tumor. Researchers believe the potential benefit of ACE inhibitors against cancer may be due to the suppression of tumor angiogenesis by blocking the angiogenic factor, vascular endothelial growth factor (VEGF), which is believed to play a significant role in the growth and reproduction of tumors. ACE inhibitors have also been reported to attenuate the carcinogenesis process in which angiogenesis is involved. Since ACE inhibitors are already in widespread clinical case without any serious adverse effects, they may represent a potential new strategy for cancer therapy and chemoprevention, researchers believe.