Clinical response to morphine in cancer patients and genetic variation in candidate genes

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 mu- opioid receptor, beta 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 beta 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 ( chi(2) = 3.86, P = 0.049) in the stat6 gene. No differences were seen in genotype or allele frequencies of SNPs in the mu-opioid receptor gene or UGT2B7 gene. This study presents novel data suggesting that variation in genes involved in m- opioid receptor signalling influence clinical response to morphine.