Abstract
(1) Background: The pleiotropic effects of statins may explain a chemoprotective action against colorectal cancer (CRC). Many studies have tested this hypothesis, but results have been inconsistent so far. Moreover, few have examined statins individually which is important for determining whether there is a class effect and if lipophilicity and intensity may play a role. (2) Methods: From 2001–2014, we carried out a study comprised of 15,491 incident CRC cases and 60,000 matched controls extracted from the primary healthcare database BIFAP. We fit a logistic regression model to compute the adjusted-odds ratios (AOR) with their 95% confidence intervals (CIs). Additionally, we carried out a systematic review and meta-analysis. (3) Results: Current use of statins showed a reduced risk of CRC (AOR = 0.87; 95% CI: 0.83–0.91) not sustained after discontinuation. The association was time-dependent, starting early (AOR6months–1year = 0.85; 95% CI: 0.76–0.96) but weakened beyond 3-years. A class effect was suggested, although only significant for simvastatin and rosuvastatin. The risk reduction was more marked among individuals aged 70 or younger, and among moderate-high intensity users. Forty-eight studies were included in the meta-analysis (pooled-effect-size = 0.90; 95% CI: 0.86–0.93). (4) Conclusions: Results from the case-control study and the pooled evidence support a moderate chemoprotective effect of statins on CRC risk, modified by duration, intensity, and age.
Highlights
In 2020, colorectal cancer (CRC) was the third type in number of new cases worldwide and the first most incident in Europe, after excluding gender-specific types [1]
From a study cohort of 5,310,198 subjects throughout the study period, we identified and extracted 15,491 incident CRC cases and 60,000 controls successfully matched by age, sex and year of index date (Figure 1)
Alcohol abusers, and history of diabetes, gout, hypertension, angina pectoris, peripheral artery disease and acute GI disorders were more prevalent among cases resulting in a crude positive association with CRC, which was still present after full adjustment, excepting for diabetes, hypertension, angina pectoris, constipation, non-complicated upper GI disorders and dyspepsia that lost the statistical significance
Summary
In 2020, colorectal cancer (CRC) was the third type in number of new cases worldwide and the first most incident in Europe, after excluding gender-specific types [1]. Task Force (USPSTF) endorsed the use of low-dose aspirin for the primary prevention of cardiovascular disease (CVD) and CRC in a specific population [9] They recently revised and downgraded that statement [10] once the net benefit of low-dose aspirin for primary prevention of CVD was put into question [11–13]. Along these lines, statins, of which among their pleiotropic effects include anti-inflammatory and anti-proliferative actions [14], have been widely studied in observational and post-hoc analyses from randomized clinical trials as potential chemoprotective agents against CRC, but no conclusive results have been reached; this is mostly due to the high heterogeneity across studies [15]
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