Ann Arbor, MI - A retrospective study published this week in the May 26, 2005 issue of the New England Journal of Medicine offers additional evidence that statins might one day be used to prevent cancer [1]. In this most recent analysis, statin therapy was associated with a statistically significant 47% relative reduction in the risk of colorectal cancer after adjustment for other known risk factors.

"Our data indicate that there is a strong inverse association between the risk of colorectal cancer and the long-term use of statins," write lead investigator Dr Jenny Poynter (University of Michigan, Ann Arbor) and colleagues. "This association is consistent with preclinical data suggesting that it is biologically plausible that statins may have a role in colorectal cancer as well as evidence from secondary analyses of some, but not all, randomized, controlled trials."

Investigators analyzed data from the Molecular Epidemiology of Colorectal Cancer study, a population-based case-control study of colorectal cancer in northern Israel. Eligible patients received a diagnosis of colorectal cancer between 1998 and 2004 and were compared with controls matched according to age, sex, clinic, and ethnicity. Interviews were conducted to determine statin use in the two groups and verified by examining a subgroup of available prescription records.

In an analysis of 1953 patients with colorectal cancer and 2015 control subjects, the use of statins for at least five years was associated with a significantly reduced relative risk of colorectal cancer. When investigators analyzed the data separately for cancers of the colon and the rectum, the inverse correlation remained.

"Statins have a variety of pathways by which they could exert their anticancer effects," senior investigator Dr Gad Rennert (Technion-Israel Institute of Technology, Haifa, Israel) told heartwire. "Most important, they are antiproliferative and anti-inflammatory. Just last week at the meeting of the American Society of Clinical Oncology, three papers were presented showing preventive effects against breast, lung, and prostate cancers. This is in line with the general antiproliferative mechanism of action that should not be [cancer] site-specific."

In this study, simvastatin (Zocor, Merck & Co) and pravastatin (Pravachol, Bristol-Myers Squibb) were the two most commonly used statins, accounting for 56% and 42% of use, respectively. In an unadjusted analysis, the strength of the association between statin use and reduced risk of cancer was similar for both drugs. The use of fibric-acid derivatives was not associated with a reduced risk in colorectal cancer, although the number of patients taking these agents was small.

Rennert told heartwire that next steps should involve randomized, controlled clinical studies, as the absolute reduction in risk is likely small. He pointed out that such trials might be difficult due to the increased prevalence of statin use and possible selection biases.

"There is some sincere skepticism as to the chance of actually carrying out a strong trial," said Rennert. "As it is already, more than 15% of the adult population uses statins. It is left therefore to see whether this current use, which became more and more fashionable in recent years, will potentially translate into some decline in colorectal-cancer rates. Such decline, even if demonstrated, however, will be hard to attribute to statin use [without a clinical trial]."

In an editorial accompanying the published study, Drs Ernest Hawk and Jaye Viner (National Cancer Institute, Bethesda, MD) agreed that the potential of statins to prevent cancer warrants further study [2]. "It is too early to recommend statins as chemopreventive agents against colorectal cancer outside the context of a clinical trial."

Hawk and Viner stress that the unique public-health potential of statins to prevent multiple diseases requires serious consideration of trial designs, especially with regard to appropriate cohorts and study end points. They point out that while placebo-controlled trials are still ethically possible in lower-risk patients, the window of opportunity is closing, especially with current trends toward greater use of statins in larger segments of the population.

The National Cancer Institute is currently funding two small studies that will examine the role of statins in preventing or reversing precancerous changes linked to either colon cancer or melanoma.