title: The Val158Met polymorphism of the human catechol-O-methyltransferase (COMT) gene may influence morphine requirements in cancer pain patients.
abstract: Catechol-O-methyltransferase (COMT) inactivates dopamine, epinephrine and norepinephrine in the nervous system. A common functional polymorphism (Val158Met) leads to a three- to-four-fold variation in the COMT enzyme activity, the Met form displaying lower enzymatic activity. The Val158Met polymorphism affects pain perception, and subjects with the Met/Met genotype have the most pronounced response to experimental pain. Based on this information we analyzed the influence from the COMT Val158Met polymorphism on the efficacy of morphine in a cohort of patients suffering from cancer pain. We genotyped 207 Caucasian cancer patients on morphine treatment with respect to the Val158Met polymorphism and compared the morphine doses, serum concentrations of morphine and morphine metabolites between the genotype groups. Patients with the Val/Val genotype (n=44) needed more morphine (155+/-160 mg/24 h) when compared to the Val/Met (117+/-100 mg/24 h; n=96) and the Met/Met genotype (95+/-99 mg/24 h; n=67) groups (P=0.025). This difference was not explained by other factors such as duration of morphine treatment, performance status, time since diagnosis, perceived pain intensity, adverse symptoms, or time until death. These results suggest that genetic variation in the COMT gene may contribute to variability in the efficacy of morphine in cancer pain treatment.
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), N-7489 Trondheim, Norway.
authors.forename: Trude Teoline
authors.initials: TT
authors.lastname: Rakvåg
authors.forename: Pål
authors.initials: P
authors.lastname: Klepstad
authors.forename: Cecilie
authors.initials: C
authors.lastname: Baar
authors.forename: Tor-Morten
authors.initials: TM
authors.lastname: Kvam
authors.forename: Ola
authors.initials: O
authors.lastname: Dale
authors.forename: Stein
authors.initials: S
authors.lastname: Kaasa
authors.forename: Hans Einar
authors.initials: HE
authors.lastname: Krokan
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
mesh_terms: D000368:Aged; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D008875:Middle Aged; D009020:Morphine / Q000627:therapeutic use; D009294:Narcotics / Q000627:therapeutic use; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D010147:Pain Measurement; D017288:Pain Threshold / Q000502:physiology*; D010597:Pharmacogenetics / Q000379:methods; D011110:Polymorphism, Genetic; D012189:Retrospective Studies; D018709:Statistics, Nonparametric; D014633:Valine / Q000235:genetics
chemical_list: D009294:Narcotics; D009020:Morphine; D008715:Methionine; D002394:Catechol O-Methyltransferase; D014633:Valine