Table 3 Characteristics of studies on the association of OPRM1 A11G and response to opioids for pain management in advanced cancer.
Study references | Study site, design and included participants | Intervention | Genotype distribution | Allele frequency | Study findings |
|---|---|---|---|---|---|
Campa et al. (2008)12 | 137 cancer patients receiving morphine, Italy | Morphine (oral) | AA (n = 106) AG (n = 22) GG (n = 10) | A = 0.848 G = 0.152 | AA genotype associated with a significant decrease in pain score from baseline compared to AG and GG |
Chatti et al. (2016)16 | 129 patients with cancer pain, Tunisia | Morphine (oral) | AA (n = 98) AG (n = 31) GG (n = 0) | A = 0.880 G = 0.120 | No significant association between genotypes and the dose of morphine needed for pain relief |
Droney et al. (2013)17 | 249 patients with cancer pain, UK (Caucasian) | Morphine (oral) | AA (n = 183) AG (n = 58) GG (n = 8) | A = 0.851 G = 0.149 | No association between genotypes and residual pain (pain score) or central side-effects in a principal components analysis study |
Gong et al. (2013)13 | 112 patients with moderate to severe cancer pain, China | Opioids (morphine, tramadol, oxycodone, fentanyl) | AA (n = 44) AG (n = 50) GG (n = 18) | A = 0.616* G = 0.384 | AG and GG genotype associated with a significantly higher dose than AA, and GG requiring a significantly higher dose than both AG and AA |
Hajj et al. (2017)10 | 89 palliative care patients with advanced cancer, Lebanon | Morphine (IV) | AA (n = 69) AG (n = 20) GG (n = 0) | A = 0.888 G = 0.112 | AG genotype associated with significantly higher dose of morphine than AA |
Klepstad et al. (2004)11 Reyes-Gibby et al. (2007) | 99 advanced cancer patients with adequate analgesia (BPI average pain score < 4), Norway Same population as above | Morphine (oral) | AA (n = 78) AG (n = 17) GG (n = 4) | A = 0.874 G = 0.126 | AG genotype associated with a significantly higher pain score, GG associated with significantly higher dose Patients jointly carrying AA and Met/Met for COMT rs4680 (Val158Met) required the lowest dose to achieve pain relief |
Klepstad et al. (2011)18 | 1745 cancer patients with moderate to severe pain at 17 centres including Denmark, Finland, Germany, Great Britain, Iceland, Italy, Lithuania, Norway, Sweden, Switzerland | Opioids (morphine, oxycodone, fentanyl, other opioids) | AA (n = 1335) AG (n = 385) GG (n = 25) | A = 0.875 G = 0.125 | No significant associations between genotypes and opioid dose in the development (n = 1177) or validation (n = 568) sample |
Li et al. (2016)14 | 59 patients with severe cancer-induced pain, China | Oxycodone (oral sustained-release) | AA (n = 23) AG (n = 28) GG (n = 8) | A = 0.627* G = 0.373 | AG and GG genotype associated with a significantly higher dose than AA, with adverse effects not associated with the polymorphism |
Matic et al. (2017)28 | 238 advanced cancer patients referred to a pain consultation service due to inadequate analgesia, Netherlands | Opioids (fentanyl, oxycodone, hydromorphone, morphine, buprenorphine) with 9% requiring ketamine as an adjuvant analgesic | AA (n = 192) AG (n = 45) GG (n = 1) | A = 0.901 G = 0.099 | A trending increase in change of morphine equivalent dose increase from baseline was seen for 118A>G, which converted to a significant 50% higher required dose increase for those patients who also carried the COMT rs4680 (Val158Val) genotype |
Matsuoka et al. (2012)19 | 41 opioid naïve patients with malignant neoplasms, Japan | Morphine (mixed routes) | AA (n = 12) AG (n = 21) GG (n = 8) | A = 0.549* G = 0.451 | No association was observed between the OPRM1 118A>G genotype and the plasma concentration or the required dose of morphine |
Naito et al. (2011)20 | 62 cancer patients receiving oxycodone in a dose escalation study, Japan | Oxycodone (oral extended-release) | AA (n = 19) AG + GG (n = 43) | A = 0.581* G = 0.419 | No significant association observed in the incidence of dose escalation between genotypes |
Oosten et al. (2016)21 | 339 moderate-to-severe cancer-related pain, Netherlands | Opioids (oxycodone, morphine, fentanyl, hydromorphone) | AA (n = 269) AG + GG (n = 70) | – | No association between genotypes and opioid failure, defined as rotation to another opioid or treatment with intrathecal opioids due to insufficient pain control and/or side effects, or the use of palliative sedation because of refractory symptoms associated with opioid treatment in the dying phase |
Ross et al. (2005)22 | 156 cancer patients (117 controls and 39 switchers), UK (Caucasian) | Opioids (morphine, oxycodone, other opioids) | AA (n = 114) AG (n = 37) GG (n = 5) | A = 0.849 G = 0.151 | No association between genotypes of patients who responded to morphine (control) vs those switching to an alternate opioid |
Takemura et al. (2023)23 | 222 in-patients receiving cancer pain treatment as part of an opioid introduction or opioid rotation strategy, Japan | Opioids (fentanyl, hydromorphone, oxycodone, methadone, tapentadol) | AA (n = 81) AG (n = 74) GG (n = 67) | A = 0.532* G = 0.468 | No association for those patients receiving tapentadol (n = 28) and methadone (n = 25), but a significantly smaller reduction pain score in G-allele carriers for hydromorphone (n = 67), oxycodone (n = 26), and fentanyl (n = 76) groups |
Ying et al. (2016)15 | 66 Han Chinese patients with medium and severe cancer pain, China | Opioids (oxycodone, morphine, fentanyl) | AA (n = 24) AG (n = 35) GG (n = 7) | A = 0.629* G = 0.371 | AG and GG genotype associated with a significantly higher opioid dose than AA |
