Statins and Colorectal Cancer

Paul Lochhead; Andrew T. Chan

Disclosures

Clin Gastroenterol Hepatol. 2013;11(2):109-118. 

In This Article

Summary and Future Perspectives

An abundance of experimental data have provided a variety of biologically plausible mechanisms through which statins might affect the initiation or evolution of colorectal neoplasia. Evidence from clinical studies is, however, conflicting. Studies supporting a chemopreventive role for statins in colorectal neoplasia are relatively few in number and are almost exclusively of retrospective observational design. Although the magnitude of risk reduction observed in the case-control study by Poynter et al[26] was impressive, collective analysis of observational studies by meta-analysis suggests a more modest effect size.[61,85] Collectively, the influence of statin use on colorectal cancer in cardiovascular RCTs appears neutral. Taken together with the null observational analysis of statin use in the APC trial, this has certainly dampened enthusiasm for statins as chemopreventive agents. It remains conceivable, however, that statin use for longer periods, at higher doses, in combination with other agents, or in genetically defined subgroups (such as those with HMG-CoA reductase gene polymorphisms), may influence the risk of colorectal neoplasia.

It has been argued that the duration of chemoprevention trials should be at least as long as the latency period of many cancers.[101] Follow-up duration is a major shortcoming of prospective analyses of statins and colorectal neoplasia to date, and attempting to address the latency period of colorectal cancer represents a logistic and financial challenge to future studies. In addition, given that the prevalence of statin use is high among those likely to be target subjects for future statin chemoprevention trials, establishing and maintaining a statin-free control arm is likely to become increasingly difficult.

From a clinical practice perspective, at present, there is insufficient evidence to recommend the use of statins for colorectal cancer chemoprevention. However, follow-up will continue to accrue for statin users in prospective cohorts and participants of completed intervention studies. Future analyses, benefitting from more lengthy exposure to statins, and increased time at risk of colorectal cancer, may prove enlightening. The outcome of ongoing clinical studies of statins in high-risk populations for polyp prevention, and as adjuvant therapeutic agents, will eagerly be awaited.

Comments

3090D553-9492-4563-8681-AD288FA52ACE

processing....