Relationship between drugs affecting the renin-angiotensin system and colorectal cancer: The MCC-Spain study

Abstract

The potential protective effect of Renin-angiotensin system (RAS) inhibitors is a subject of increasing interest due to their possible role as chemopreventive agents against colorectal cancer (CRC). To evaluate this association, we conducted a case-control study with 2,165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3,912 population controls frequency matched (by age, sex and region) from the Spanish multicenter case-control study MCC-Spain. We found a significant protective effect of the Angiotensin-converting enzyme Inhibitors (ACEIs) against CRC, limited to the under-65 years group (OR=0.65 95%CI (0.48-0.89)) and to a lesser degree to men (OR=0.81 95%CI (0.66-0.99). In contrast, the angiotensin receptor blockers (ARBs) did not show a significant effect. Regarding the duration of use, a greater protection was observed in men as the length of consumption increases. In contrast, in the under-65 stratum, the strongest association was found in short-term treatments. Finally, by analyzing ACEIs effect by colon subsite, we found no differences, except for under 65 years old, where the maximum protection was seen in the proximal intestine, descending in the distal and rectum (without statistical significance). In conclusion, our study shows a protective effect on CRC of the ACEis limited to males and people under 65 years old, which increases in proximal colon in the latter. If confirmed, these results may suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.

Alterations in Gene Expression of Renin-Angiotensin System Components and Related Proteins in Colorectal Cancer

“…Increased AGTR1 gene expression is associated with breast cancer [ 85 ], and ARBs inhibit mammary tumor formation in mice [ 86 , 87 ]. Similar, to the observation of no increase in AT1R gene expression in this study, ARB usage did not have a protective effect against CRC in a retrospective study of a large Spanish population [ 96 ].…”

“…There is considerable variance in the reported effects of ACE inhibitors on cancer risk with some studies of CRC showing a chemoprotective effect [ 18 , 109 ]. Beneficial effects of ACE inhibitors on CRC were found to be greatest in men under 65 years of age [ 96 ].…”

Renin–angiotensin system inhibitor use and colorectal cancer risk and mortality: A dose–response meta analysis

“…A total of 931 related articles were obtained in the initial inspection, which were screened by layer and 16 were finally included, comprising 16 randomized controlled trials involving 2,847,597 participants. 9 – 24 The flow chart of the literature search is presented in Figure 1 . The characteristics of the included studies are shown in Tables 1 and 2 .…”

Long‐term antihypertensive drug use and risk of cancer: The Japan Public Health Center‐based prospective study

“…However, in 2010, Sipahi et al 3 suggested that ARB increased the risk of developing cancer and, conversely, the results of Bangalore et al 4 reported in 2011 that they were unrelated. In recent studies on various cancers and antihypertensive drugs, it has been reported that angiotensin‐converting enzyme inhibitor (ACE‐I) and ARB are associated with a decrease in the incidence of colorectal cancer, 5 while for lung cancer, there have been reports that ACE‐I is associated with increased cancer incidence 6 . Moreover, for breast cancer, it has been reported that antihypertensive drugs (ARB, ACE‐I, Ca blocker, β‐blocker, diuretics) are either associated with an increase in cancer incidence 7,8 or are not related 9 .…”

“…that angiotensin-converting enzyme inhibitor (ACE-I) and ARB are associated with a decrease in the incidence of colorectal cancer, 5 while for lung cancer, there have been reports that ACE-I is associated with increased cancer incidence. 6 Moreover, for breast cancer, it has been reported that antihypertensive drugs (ARB, ACE-I, Ca blocker, β-blocker, diuretics) are either associated with an increase in cancer incidence 7,8 or are not related.…”