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 2165 cases of colorectal cancer, diagnosed between 2007 and 2012, and 3912 population controls frequency matched (by age, sex and region) fromthe Spanishmulticenter case-control studyMCCSpain. 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 tomen (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 resultsmay suggest a novel approach to proximal CRC prevention, given the shortcomings of colonoscopy screening in this location.

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