There is extensive debate regarding the protective effect of 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) on colorectal cancer (CRC).
We investigated the synergistic effect of simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor plus radiation therapy, on the proliferation and survival of gastric cancer (GC) and colorectal cancer (CRC) cells.
Compared with nonusers, the unadjusted odds ratio of CRC among statin users with the A/A genotype of rs12654264 in HMGCR was 0.3 (95% confidence interval, 0.18-0.51) and among statin users with the T/T genotype was 0.66 (95% confidence interval, 0.41-1.06; P-interaction = 0.0012).
Here we describe how these studies lead to the discovery that HMGCR alternative splicing of exon 13 is not only a marker, but also a determinant of statin efficacy; not only for the treatment of hypercholesterolemia, but also as a chemopreventive agent for colorectal cancer.