Abstract
Despite increased attention on assessment and management, pain remains the most persistent symptom in patients with cancer, in particular in end-of-life settings, with detrimental impact on their quality-of-life (QOL). We conducted this study to evaluate the added value of determining some genetic and non-genetic factors to optimize cancer pain treatment. Eighty-nine patients were included in the study for the evaluation of palliative cancer pain management. The regression analysis showed that age, OPRM1 single nucleotide polymorphism (SNP), as well as the duration of morphine treatment were significantly associated with morphine doses at 24 h (given by infusion pump; p = 0.043, 0.029, and <0.001, respectively). The mean doses of morphine decreased with age but increased with the duration of morphine treatment. In addition, patients with AG genotype c.118A>G OPRM1 needed a higher dose of morphine than AA patients. Moreover, metastases, OPRM1 SNP, age, and gender were significantly associated with the QOL in our population. In particular, AA patients for OPRM1 SNP had significantly lower cognitive function than AG patients, a result not previously reported in the literature. These findings could help increase the effectiveness of morphine treatment and enhance the QOL of patients in regards to personalized medicine.
Highlights
Pain is the most persistent and common symptom in cancer patients, especially in the end-of-life setting of palliative care
American Society of Clinical Oncology (ASCO) meeting, health care professionals, as well as researchers have highlighted the importance of pain control while preserving the quality-of-life (QOL) of patients, the latter being recognized as one of the most important parameters to measure while assessing medical therapies
Numerous single nucleotide polymorphism (SNP) in the OPRM1 have been identified, but only a few have been explored for possible relevance in opioid analgesia, including the c.118A>G SNP; patients carrying the GG genotype required higher morphine doses compared to AA patients [4,5]
Summary
Pain is the most persistent and common symptom in cancer patients, especially in the end-of-life setting of palliative care. Numerous SNPs in the OPRM1 have been identified, but only a few have been explored for possible relevance in opioid analgesia, including the c.118A>G SNP (rs1799971); patients carrying the GG genotype required higher morphine doses compared to AA patients [4,5] Another relevant gene that has been identified as an important modulator of opioid efficacy and toxicity is the COMT gene encoding the catechol-O-methlytransferase. The c.3435C>T SNP (rs1045642) of ABCB1 is an interesting factor affecting the pharmacokinetics of morphine This gene encodes for P-glycoprotein (P-gp), a transmembrane efflux transporter that belongs to the family of ATP binding cassette (ABC) transporters and the variant results in a C-to-T substitution at nucleotide 3435 that has been associated with a reduced expression of duodenal P-gp in homozygous TT patients [10]. Publications have shown that ABCB1 TT patients were “good responders” compared to CC patients [12] and required fewer morphine doses for pain relief [9,13,14]
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