Patients with inflammatory bowel disease who were prescribed statins had 65% lower odds of subsequent colorectal cancer, compared with other IBD patients, even after controlling for multiple potential confounders, researchers reported in Clinical Gastroenterology and Hepatology.
“Further confirmation from other cohorts may provide support for the use of statins as a chemopreventive in patients with IBD,” said Dr. Ashwin Ananthakrishnan of Massachusetts General Hospital in Boston, and his associates.
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Patients with long-standing ulcerative colitis or colonic Crohn’s disease have about twice the risk of colorectal cancer (CRC), compared with the general population, and up to an 18% lifetime risk of CRC by 30 years after diagnosis, the researchers noted. Early results supporting mesalamine as chemoprophylaxis did not hold up in later trials. Although several studies suggested that statins might help prevent sporadic colon cancer, the only such study in IBD patients was small and did not control for key covariates such as smoking, the investigators added. Therefore, they collected data from 11,001 patients with IBD who were seen at Boston area hospitals between 1998 and 2010. They identified CRC diagnoses based on ICD-9 codes, and analyzed electronic prescriptions to see whether and when patients had used statins (Clin Gastroenterol Hepatol. 2016 Feb 21. doi: 10.1016/j.cgh.2016.02.017).
A total of 1,376 patients (12.5%) were prescribed at least one statin. Over 9 years of follow-up, 2% of statin users developed CRC, compared with 3% of nonusers (age-adjusted odds ratio, 0.35; 95% confidence interval, 0.24-0.53). Statin users were more likely to be older, male, white, smokers, and had more comorbidities than nonusers. Nonetheless, the protective effect of statins remained significant after controlling for demographic factors, smoking status, number of colonoscopies, use of steroids and immunomodulators, the presence of primary sclerosing cholangitis, and increases in inflammatory biomarkers (OR, 0.42; 95% CI, 0.28-0.62). The effect occurred for both Crohn’s disease and ulcerative colitis. Notably, the inverse association was even stronger among patients who had been prescribed at least two statins or who had at least a 2-year interval between statin use and CRC diagnosis.
Statins might help prevent CRC through HMG-CoA reductase inhibition and other mechanisms, according to the researchers. By inhibiting HMG-CoA reductase, statins lower production of farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are needed for post-translational activation of Ras, Rho, and other proteins that are overexpressed in CRC and that have been linked to tumor invasion. Statins also might help prevent CRC through antioxidant effects or by inhibiting inflammation, cell adhesion, and angiogenesis, the investigators added. “Although we did not see a difference in median C-reactive protein levels between statin users and nonusers, statin users were less likely to require immunomodulator or biologic therapy for their IBD, supporting a potential anti-inflammatory role for statins.”
Because patients mainly were treated at two tertiary referral hospitals, they may have had more severe disease than the general population of patients with IBD, the investigators acknowledged. They noted that in some meta-analyses, referral center studies yielded chemopreventive effects that did not hold up in population-based cohorts.
The study was funded by the National Institutes of Health, the American Gastroenterological Association, and the Harold and Duval Bowen Fund. The researchers had no disclosures.