CYP genotypes influence the effect of tamoxifen therapy on serum lipids

Abstract

Beneficial effects of tamoxifen therapy on LDL-cholesterol have been reported in several studies. We examined the relationship between genetic polymorphisms in CYP2D6 (*1, *4, *5, *6 and *10) and CYP2C9 (*1, *2 and *3) genes and serum lipid profile in 28 women who took tamoxifen (20mg/day) for the management of breast cancer. The fasting serum lipid profiles were evaluated before starting tamoxifen therapy and at the end of four months of treatment. The total and LDL-cholesterol lowering effect of tamoxifen was not significantly different among groups carrying different CYP2D6 genotype variants. The same was true for CYP2C9 groups. A significant decrease in total and LDL-cholesterol was noted in women who carried a combination of *1/*1 variants of CYP2D6 and CYP2C9 genes or a combination including *1/*1of either CYP combined with any other variant of the other CYP (p=0.0003 and 0.0001 for total and LDL cholesterol respectively). CYP2D6 *1/*10 combined with a heterozygous variant of CYP2C9 did not adversely influence the beneficial effect of tamoxifen consistent with the *10 variant only partially decreasing enzyme activity. No beneficial effect of tamoxifen was seen in the group of patients who carried variants of both CYPs. The use of new multi-comparison algorithms to evaluate the effects of multiple genetic variants on robust measures of drug response is critical to the demonstration of predictive pharmacogenetic patterns. Clinical Pharmacology & Therapeutics (2004) 75, P69–P69; doi: 10.1016/j.clpt.2003.11.261