Angiotensin-converting enzyme inhibitor (ACE-i) or angiotensin II receptor blocker (ARB) medications are prescribed for conditions such as heart failure, high blood pressure or heart disease. These medications block angiotensin, a chemical that causes arteries to become narrow. ACE inhibitors inhibit the angiotensinogen converting enzyme (ACE) with a competitive mechanism at the catalytic site. Receptor or sartanic antagonists, on the other hand, interfere with the cellular signals triggered by AT2 after interaction with its receptor (AT2R). Doctors commonly prescribe these medications to people with high blood pressure to relax and open blood vessels, thereby lowering blood pressure. According to new research published today in the journal Hypertension, these medications commonly prescribed to treat high blood pressure may also reduce patients’ colorectal cancer risk. Colorectal cancer is the third most common cancer and is the second leading cause of cancer death worldwide.
The roles of ACE inhibitors and ARBs on cancer development are controversial and, in some cases, study findings are conflicting. Results of previous studies have been limited by several factors including a small number of patients and data only on short-term follow-ups. Based on the findings of this large study, taking these medications may also reduce colorectal cancer risk. Researchers reviewed health records of 187,897 adult patients in Hong Kong from 2005 to 2013, with a negative baseline colonoscopy for colorectal cancer. This is a retrospective study, looking back at whether patients on these medications developed colorectal cancer. The analysis found that those who took ACE-i or ARBs had a 22% lower risk of developing colorectal cancer in the subsequent three years. In addition, the benefits of ACE-i and ARBs were seen in patients 55 or older and those with a history of colon polyps; and the benefit associated with the medications was limited to the first three years after the negative baseline colonoscopy.
Angiotensin 2 is a peptide hormone and like many other human peptides called growth factors, it may trigger cellular proliferation. In tissues that cannot replicate their cell content, its effect translates in cellular enlargement (hypertrophy). On the contrary, in sensitive and actively replicating cells, it may drive cell proliferation. This may be true for cancer cells as well, since an indipendent research group from Kagawa University in Japan has demonstrated that telmisartan, a commonly prescribed ARB, suppresses stomach cancer cell growth. The mechanism started from the inhibition of the phosphorylation of epidermal growth factor receptor (EGFR), a common step of cellular cross talk between angiotensin and growth factors. As a consequence, several intracellular transducing pathways were negatively influenced and cells stopped entering their cycling. AT2R has been seen upregulated in colon cancers; it likely uses paracrine angiotensin neural network to enhance its local growth and peripheral spreading (metastasis).
Wai K. Leung, MD, Study Author and Clinical Professor of Medicine at the University of Hong Kong, commented: “This is the first study to show the potential beneficial effects of ACE inhibitors and ARBs on colorectal cancer development, based on a large group of patients who were colorectal cancer-free at the beginning of the study. Our results provide new insights on the potential role of these medications for colorectal cancer prevention. While ACE-i and ARBs are taken by patients with high blood pressure, heart failure, and kidney diseases, the reduction in colorectal cancer risk may be an additional factor for physicians to consider when choosing anti-hypertensive medications. However, our data should be verified with a prospective randomized controlled study, which would actively follow patients to determine the potential benefits of these medications on colorectal cancer risk.
- Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.
Cheung KS et al. Hypertension 2020: HYPERTENSIONAHA12015317.
Fujita N et al., Masaki T. Oncol Rep. 2020 Jul; 44(1):339-348.
Kasprzak A, Adamek A.Int J Mol Sci. 2020 May 15; 21(10):3494.
de Paula Gonzaga ALAC et al. Curr Drug Targets. 2020 Feb 10.
Zhang K et al. Artif Cells Nanomed Biotechnol. 2019; 47(1):2500.