title: Clinical response to morphine in cancer patients and genetic variation in candidate genes.
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 mu-opioid receptor, betaarrestin2, 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 betaarrestin2 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 mu-opioid receptor signalling influence clinical response to morphine.
authors.affiliation: Department of Clinical Genomics, Imperial College, London, UK. joy.ross@rmhnthames.nhs.uk
authors.forename: J R
authors.initials: JR
authors.lastname: Ross
authors.forename: D
authors.initials: D
authors.lastname: Rutter
authors.forename: K
authors.initials: K
authors.lastname: Welsh
authors.forename: S P
authors.initials: SP
authors.lastname: Joel
authors.forename: K
authors.initials: K
authors.lastname: Goller
authors.forename: A U
authors.initials: AU
authors.lastname: Wells
authors.forename: R
authors.initials: R
authors.lastname: Du Bois
authors.forename: J
authors.initials: J
authors.lastname: Riley
mesh_terms: D000483:Alleles; D000701:Analgesics, Opioid / Q000627:therapeutic use*; D019390:Arrestins / Q000235:genetics*; D003221:Confusion / Q000139:chemically induced; D005260:Female; D005787:Gene Frequency; D014453:Glucuronosyltransferase / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009020:Morphine / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D009325:Nausea / Q000139:chemically induced; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D010147:Pain Measurement; D010148:Intractable Pain / Q000188:drug therapy* / Q000235:genetics*; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D017450:Receptors, Opioid, mu / Q000235:genetics / Q000378:metabolism; D000071557:beta-Arrestins
chemical_list: D000701:Analgesics, Opioid; D019390:Arrestins; D017450:Receptors, Opioid, mu; D000071557:beta-Arrestins; D009020:Morphine; C491474:UGT2B7 protein, human; D014453:Glucuronosyltransferase