A systematic meta-analysis has shown that statin users had a significantly reduced risk of colorectal cancer. The study included patients with and without inflammatory bowel disease, which is associated with an increased risk of this type of cancer. The largest chemopreventive effect was observed in patients with this gastrointestinal disorder, according to Kevin Singh, MD, of NYU Langone Medical Center, New York, who presented the findings during the virtual edition of the American College of Gastroenterology (ACG) 2020 Annual Scientific Meeting.1
“Statin use among persons without inflammatory bowel disease was associated with a significant 20% risk reduction for colorectal cancer.”— Kevin Singh, MD
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“Chemopreventive agents to reduce the risk of colorectal cancer have been studied for decades,” Dr. Singh said. Among them are nonsteroidal anti-inflammatory drugs, antihypertensives, fibrates, antiplatelet agents, vitamin D, calcium, and metformin. A large body of evidence shows the most effect is conveyed by aspirin; however, aspirin is associated with an increased risk of bleeding and is therefore not an optimal chemopreventive agent.
Individuals with inflammatory bowel disease have an increased risk for colorectal cancer. In this population, 5-aminosalicylic acid compounds, thiopurines, anti–tumor necrosis factor therapies and ursodeoxycholic acid have been studied for chemoprevention, with varying efficacy.
The Case for Statins
Statins are among the most frequently prescribed medications worldwide and are generally well tolerated. Their use has been linked to a risk reduction for several cancers, including hepatocellular carcinoma, breast, gastric, pancreatic, and biliary tract cancers. However, data supporting their use to protect against colorectal cancer have been conflicting, Dr. Singh noted.
Although it is unclear how statins may exert a protective effect, Dr. Singh said these drugs are thought to inhibit cancer-promoting proteins such as RAS in colonic epithelial cells.
A prior meta-analysis published in 2014, which included 40 studies, concluded that statins reduced the risk for colorectal cancer by 9% among individuals without inflammatory bowel disease.2 Few studies have investigated the use of statins in this population of patients. The current meta-analysis evaluated the benefit of statins in persons with and without inflammatory bowel disease.
Study Details and Results
Dr. Singh and colleagues conducted an extensive literature search of publications up to May 2020. They included studies with odds ratios (OR) that had 95% confidence intervals or presented data sufficient to calculate the OR with a 95% confidence interval (CI). They found 52 studies, including 17 cohort studies, 27 case-control studies, and 8 randomized clinical trials. The population totaled 11,459,306 individuals, of whom 2,123,293 were statin users and 9,336,013 were not.
“Statin use among persons without inflammatory bowel disease was associated with a significant 20% risk reduction for colorectal cancer (OR = 0.801; 95% CI = 0.73–0.88; P < .001),” Dr. Singh reported.
Among the subset of 17,528 individuals with inflammatory bowel disease, there were 1,994 statin users and 15,534 nonusers. Statin users were found to lower the risk for colorectal cancer in this population by 60% (OR = 0.399; 95% CI = 0.18–0.86; P = .019).
“We didn’t look at aspirin use as a confounder, but that’s going to be done in the next part of the analysis,” he said.
Dr. Singh acknowledged that “significant heterogeneity” was found within both analyses, more so in the evaluation of the inflammatory bowel disease populations “owing to differences in demographic features, ethnic groups, and risk factors for colorectal cancer.” Publication bias was not detected in the analysis of populations without inflammatory bowel disease, but it was present in the other analysis, possibly because it included observational studies alone, he said.
“Prospective randomized trials are needed to confirm the risk reduction of colorectal cancer in the inflammatory bowel disease population, including whether the effects of statins differ between patients with ulcerative colitis and Crohn’s disease,” Dr. Singh added.
DISCLOSURE: Dr. Singh reported no conflicts of interest.
1. Singh KN, Yakubov S Nadeem A: Stain use reduces the risk of colorectal cancer: An updated meta-analysis and systemic review. American College of Gastroenterology 2020 Annual Scientific Meeting. Abstract S0265. Presented October 26, 2020.
2. Lytras T, Nikolopoulos G, Bonovas S: Statins and the risk of colorectal cancer: An updated systematic review and meta-analysis of 40 studies. World J Gastroenterol 20:1858-1870, 2014.