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. Because a person inherits two variants, one from each parent, the stronger colorectal cancer protection came from individuals with the A/A HMGCR genotype, compared with those with the T/T genotype. Individuals with an A/T genotype had intermediate protection against colorectal cancer -- levels that varied between that seen for A/A and T/T genotypes.
Dr. Lipkin estimates that, in this Caucasian population, 56 percent had at least one A allele in that HMGCR genomic position.
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 colorect
|Contact: Andrew Klein|
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College