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CYP genotypes influence the effect of tamoxifen therapy on serum lipids
Author(s) -
Rehman M. I.,
Lee K.,
Bermes A.,
Skaar T.,
Arefayene M.,
Li L.,
Stearns V.,
Hayes D. F.,
Flockhart D. A.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.261
Subject(s) - tamoxifen , cyp2c9 , cyp2d6 , pharmacogenetics , genotype , pharmacology , pharmacogenomics , breast cancer , medicine , cholesterol , lipid profile , biology , endocrinology , cancer , oncology , gene , genetics
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