They then tested, in laboratory colorectal cancer cells, why the T allele might not work well with statins, and found that the protein produced by this HMGCR gene variant does not bind on to the statin like the A allele does, due to "alternative splicing" -- the production of a protein that is slightly altered.

"Carriers of the A allele express more of the full-length protein that binds statins, and are therefore more sensitive to statins and are more likely to experience the colorectal cancer risk reduction associated with long-term use. That is especially true if a person has two A alleles," says Dr. Lipkin. "Carriers of the T allele are less sensitive to statins because they are missing part of the protein that binds to statins. A protective effect against colorectal cancer development is largely absent from people who have two T alleles."

"Together, these studies provide strong evidence that these two alleles play an important role in modulation of HMGCR activity for colorectal risk reduction," Dr. Lipkin says. "We anticipate that genotyping for these alleles in patients may help identify those who are most likely to benefit from statins, and spare others who will not respond from any side effects of the drugs."

Dr. Lipkin believes most of the many statin drugs on the market work by binding on to the HMGCR protein. Most of the participants in this study used simvastatin (marketed under the trade names Zocor, Simlup, Simcard, Simvacor, and others), and pravastatin (marketed as Pravachol or Selektine).

Source: New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College