Tamoxifen (TAM) is widely used for treatment and prevention of
breast cancer. TAM is metabolized by
cytochrome P450 (CYP450)
enzymes, including
CYP3A5. Although two genetic polymorphisms in
CYP3A5 are known (
CYP3A5*3 and
CYP3A5*6), the effects of these polymorphisms on TAM metabolism, TAM side effects, and
tumor characteristics are unknown. Thus, this work tested the hypothesis that
CYP3A5 polymorphisms are associated with differential TAM levels, TAM side effects, and
tumor characteristics in
breast cancer patients. Postmenopausal women with
breast cancer (n=98) were recruited from a single
cancer center. Polymorphic status was established using polymerase chain reactions (PCR). The associations between polymorphic status, race, TAM levels, side effects, and
tumor characteristics were assessed using t-tests and logistic regression models. The data indicate that 40.7% of the
breast cancer patients had the
CYP3A5*3 polymorphism, and 9.1% had the
CYP3A5*6 polymorphism. In addition, Caucasian women were 26 times more likely to carry the
CYP3A5*3 polymorphism than African American (AA) women, whereas AA women were nine times more likely to carry the
CYP3A5*6 polymorphism than Caucasian women. No significant differences were seen in TAM or TAM metabolite levels or TAM side effects by polymorphic status. There was a significant difference, however, in mean
tumor size in women with the
CYP3A5*6 polymorphism (3.6+/-0.98 cm) compared to those without the polymorphism (2.0+/-0.18 cm) (P<0.02). Taken together, these data suggest that racial differences in
CYP3A5 polymorphisms exist although the polymorphisms do not appear to be associated with levels of TAM metabolites and side effects.