Background: Catechol-O-methyltransferase (COMT) inactivates dopamine, adrenaline and noradrenaline in the neuronal system. A common functional polymorphism (Val 158 Met) leads to a three-to-four-fold variation in the COMT enzyme activity, the Met form displaying lower enzymatic activity. Zubieta et al., have recently shown that the Val 158 Met polymorphism affects pain perception, and subjects with the Met/Met genotype have the most pronounced response to pain. We hypothesized that the Val 158 Met polymorphism could influence the need for morphine in cancer pain.
Methods: We genotyped 208 cancer pain patients on oral morphine treatment for the Val 158 Met polymorphism. Morphine doses and serum concentrations of morphine and morphine metabolites were compared between genotype groups.
Results: Patients with the Val/Val genotype (n=44) needed more morphine I153 (160) mg/24 hI when compared to the Val/Met I117 (100) mg/24 h; n=97I and the Met/Met genotype I94 (98) mg/24 h; n=68I groups (p=0.03). Patients with the different genotypes were similar in respect to other factors that could influence the need for morphine such as duration of morphine treatment, performance status, time since diagnosis, time until death, pain intensity and adverse symptoms.
Conclusions: These results indicate that genetic variation in the COMT gene might contribute to the variability in cancer pain patients' responses to morphine.