1. ¹Department of Clinical Genomics, Imperial College, London, UK
2. ²Horder Ward, Department of Palliative Medicine, Royal Marsden Hospital, London, UK
3. ³Department of Medical Oncology, St Bartholomews Hospital, London, UK

Correspondence: Dr JR Ross, Horder Ward, Department of Palliative Medicine, Royal Marsden Hospital, Fulham Road, London SW3 6JJ, UK. Tel: +44 02078082761; Fax: +44 02078082478; E-mail: joy.ross@rmh.nthames.nhs.uk

Received 5 January 2005; Revised 14 June 2005; Accepted 1 July 2005; Published online 16 August 2005.

Abstract

Morphine is the analgesic of choice for moderate to severe cancer pain; however, 10–30% of patients do not tolerate morphine. This study evaluated genetic variation in the -opioid receptor, arrestin2, stat6 and uridine diphosphate-glucuronysltransferase 2B7 (UGT2B7) genes, in patients who responded to morphine vs those who were switched to alternative opioids. We prospectively recruited and genotyped 162 Caucasian patients (117 controls, 39 switchers). Switchers, were more likely to carry the common allele at 1182 G/A, 5864 G/A, 8622T/C and 11143 G/A in the arrestin2 gene (P=0.021, 0.043, 0.013, 0.043, respectively). Switchers had increased carriage of the T allele (-1714 C/T) and a significant difference in the allelic frequency at 9065 C/T (²=3.86, P=0.049) in the stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in the -opioid receptor gene or UGT2B7 gene. This study presents novel data suggesting that variation in genes involved in -opioid receptor signalling influence clinical response to morphine.