Pharmacogenetics of pain in cancer

Abstract

The efficacy of opioids varies between individual cancer pain patients. This relates both to the needed dose and to responses to different opioids. Opioid pharmacology is complex and genes coding several pharmacological elements are proposed to explain some of the variability in opioid response. This includes opioid metabolism, opioid receptors, opioid transport through the blood–brain barrier, inflammation, and mechanisms modifying opioid signalling. Variability in CYP2D6 is established to influence the efficacy from codeine. The two other genes shown in several studies to influence opioids efficacy are the OPRM1 gene and the COMT gene. Variability in other genes are not consistently shown to influence on the efficacy from opioids, and in the only study that included a large patient cohort and a validation sample, no candidate genes were associated with opioid dose. Thus, with the exception of CYP2D6 activity and codeine, there are currently no pharmacogenetic analyses that are able to guide opioid therapy. Still, the biological phenomenon has been established, and it is expected that future research will discover the basis for why individuals vary in terms of opioid response.