Variability in UDP-glucuronosyltransferase genes and morphine metabolism: observations from a cross-sectional multicenter study in advanced cancer patients with pain

OBJECTIVEThe objective of the present study was to determine whether genetic variability in UDP-glucuronosyltransferase (UGT) genes, together with clinical factors, contribute to variability in morphine glucuronide (M6G and M3G) to morphine serum concentration ratios in patients with advanced cancer receiving chronic morphine therapy. MATERIALS AND METHODSA total of 41 polymorphisms and predicted haplotypes in the UGT2B7, UGT1A1, and UGT1A8 genes were analyzed in 759 patients who were recruited from the European Pharmacogenetic Opioid Study and received chronic morphine therapy by the oral route (n=635) or parenterally (n=124). The administration groups were analyzed separately by multiple linear regression analyses. RESULTSTwo haplotypes in UGT1A1/UGT1A8 were weak predictors of reduced M6G/morphine and M3G/morphine serum ratios after oral administration (false discovery rate-corrected P-values