Why statins work for some people, but not for all

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Washington, Apr 22 (ANI): Scientists at NewYork-Presbyterian Hospital/Weill Cornell Medical Center have found why statins- popular drugs that lower cholesterol and appear to protect against colorectal cancer development- work for some people, but not for all.

Based on their study, the researchers said that about 44 percent of Caucasians taking statins likely are not protected against cancer as well as others because they have inherited a particular gene variant.

They said that this finding might help personalize the use of statins, both by offering patients a test to determine if they have the "right" gene to benefit from current statin drugs, and by providing insight into how to create a new class of statins for those who have the "wrong" gene profile.

"Given that approximately 25 million individuals worldwide currently use statins, we anticipate this discovery may prompt development of more precise, personalized and cost-effective cancer risk reduction strategies," said the study's co-lead author, Dr. Steven M. Lipkin.

The researchers tested their hypothesis that people who don't respond well to the cholesterol-lowering ability of statins also do not benefit from recently documented protective effects of statins against colorectal cancer, and that the difference was in genetic variation that led to a different response to the drug.

In this study, the research team genotyped 40 candidate genes known to be important for synthesis and metabolism of cholesterol in people who participated in a population case-control study of colorectal cancer in northern Israel.

In the initial study, statin use was associated with a 50 percent relative risk of developing colorectal cancer in this population.

Included in the 40 genes were six SNPs, or DNA sequences, within the HMGCR gene, which produces a critical enzyme involved in formation of cholesterol.

They found one SNP within HMGCR that was associated with statin protection against colorectal cancer.

A follow-up pharmacogenetic analysis showed that the protective association was significantly stronger among individuals with what they dubbed the "A" SNP allele, or variant, compared with people who had a "T" variant.

"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," said 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. 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," added Lipkin.

The study has been published in the May issue of Cancer Prevention Research. (ANI)

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