In a study of 110 women taking the breast cancer drug anastrozole, there were significant differences in patients' blood levels of the drug that corresponded with variations in the ABCB1 gene. Furthermore, variants in the CYP19A1 gene were associated with additional joint pain and cancer recurrence in patients.
ABCB1 codes for an efflux pump (P-glycoprotein) on cells, whereas CYP19A1 codes for an enzyme responsible for a key step in the synthesis of estrogens.
"The main novelty of our study is that it provides an additional explanation for the wide variability in anastrozole concentrations displayed by breast cancer patients. We have now shown that, besides metabolism, drug transport by P-glycoprotein may also play a significant role," said Dr. Guillermo Gervasini, lead author of the British Journal of Clinical Pharmacology study. "This could have important clinical implications in terms of genetic variants or drug interactions modulating the drug's transport."
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British Journal of Clinical Pharmacology