Identification of Persons Likely to Benefit from Statin Mediated Cancer Prevention by Pharmacogenetics
Posted Oct 11 2009 5:00pm
Description of Invention: Inhibitors of 3-hydroxy-3-methylglutaryl (HMG) coenzyme A reductase (statins) are a class of well-tolerated compounds that are the most widely used cholesterol-lowering drugs in the United States. Reduced cancer risk among statin users has also been observed as a secondary outcome in randomized controlled clinical trials evaluating effects of statins on cardiovascular outcomes. However the observed cancer risk reduction varied with different clinical studies. Thus there is a need to identify individuals who would benefit from treatment with statins.
The current invention describes a pharmacogenetic method to identify candidates who are most likely to benefit from treatment with statins to reduce cancer risk, and consequently minimizing any unnecessary cost and side effects in individuals who do not benefit. Specifically, we discovered that an HMGCR genetic variant rs12654264 is associated with significantly lower colorectal cancer risk, with most of the benefit seen in HMGCoA reductase inhibitor (statin) users. We also discovered that this same HMGCR genetic variant is associated with significantly higher serum cholesterol levels in Israeli colorectal cancer patients. The same HMGCR genetic variant has also been associated with significantly higher serum cholesterol levels in two independent groups of individuals of mixed European descent [ http://www.broad.mit.edu/diabetes/scandinavs/index.html and N Engl J Med.2008 March 20;358(12):1240-1249 ( http://www.ncbi.nlm.nih.gov/pubmed/18354102?dopt )]. These data suggest that the same genetic variant modifies cholesterol metabolism in a manner that affects both colorectal cancer risk and cardiovascular risk.
Statins account for approximately 80% of the cholesterol-lowering drugs prescribed in the United States, and six statins are currently available on the U.S. market. Reduced cancer risk is also associated with statin use. This invention provides a method to indentify individuals who are most likely to benefit from cancer chemopreventive treatment with statins.
Pharmacogenetic markers can be developed to identify patient population that can be benefit from statins, therefore expands the markets of stains.
Development Status: The inventors have discovered several novel genetic variants of HMG coenzyme A reductase gene, and are further investigating the functional significance of the variants in vitro.
For Additional Information Please Contact: Betty Tong Ph.D. NIH Office of Technology Transfer 6011 Executive Blvd. Suite 325, Rockville, MD 20852 United States Email: email@example.com Phone: 301-594-6565 Fax: 301-402-0220