20.500.12556/DiRROS-19828 Association of OPRM1, MIR23B, and MIR107 genetic variability with acute pain, chronic pain and adverse effects after postoperative tramadol and paracetamol treatment in breast cancer Vpliv genetske variabilnosti OPRM1, MIR23Bin MIR107 na akutno in kronično bolečino ter neželene učinke zdravljenja s tramadolom in paracetamolom po operaciji raka dojk Background. Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its anal-gesic activity is due to the activation of the μ-opioid receptor, encoded by the OPRM1 gene. This study investigated the association of genetic variability in OPRM1 and its regulatory miRNA genes with outcomes of tramadol/paraceta-mol treatment after breast cancer surgery with axillary lymphadenectomy.Patients and methods. The study included 113 breast cancer patients after breast cancer surgery with axillary lymphadenectomy treated with either 75/650 mg or 37.5/325 mg of tramadol with paracetamol for pain relief within the randomized clinical trial KCT 04/2015-DORETAonko/si at the Institute of Oncology Ljubljana. All patients were geno-typed for OPRM1 rs1799971 and rs677830, MIR23B rs1011784, and MIR107 rs2296616 using competitive allele-specific PCR. The association of genetic factors with acute and chronic pain as well as adverse effects of tramadol treatment was evaluated using logistic regression, Fisher’s exact test, and Mann-Whitney test.Results.The investigated OPRM1 related polymorphisms were not associated with acute pain assessed with the VAS scale within four weeks after surgery (all P > 0.05). Carriers of at least one polymorphic OPRM1 rs1799971 allele had a higher risk of constipation in the first four weeks after surgery compared to non-carriers (OR = 4.5, 95% CI = 1.6–12.64, P = 0.004). Carriers of at least one polymorphic OPRM1 rs677830 allele had a higher risk of constipation after third week of tramadol treatment (OR = 3.11, 95% CI = 1.08–8.89, P = 0.035). Furthermore, carriers of two polymorphic MIR23Brs1011784 alleles had a higher risk of nausea after 28 days of tramadol treatment (OR = 7.35, 95% CI = 1.27–42.6, P = 0.026), while heterozygotes for MIR107 rs2296616 allele had a lower risk of nausea after 21 days of tramadol treatment (OR = 0.21, 95% CI = 0.05–0.87, P = 0.031). In carriers of two polymorphic MIR107 rs2296616 alleles, chronic pain was significantly more common than in carriers of two wild-type alleles (P = 0.004). Carriers of at least one polymorphic MIR23B rs1011784 allele experienced more neuropathic pain after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07–7.59, P = 0.036), while carriers of at least one polymorphic OPRM1 rs677830 allele experienced less neuropathic pain compared to carriers of two wild-type alleles (OR = 0.38, 95% CI = 0.15–0.99, P = 0.047).Conclusions.Genetic variability of OPRM1 and genes coding for miRNAs that could affect OPRM1 expression may be associated with adverse effects of tramadol/paracetamol treatment as well as with chronic and neuropathic pain after breast cancer surgery with axillary lymphadenectomy. operacija raka na dojki zdravljenje bolečine tramadol breast cancer surgery pain treatment tramadol true false true Association of Radiology and Oncology Ljubljana Angleški jezik Slovenski jezik by Authors Neznano 2024-07-25 13:31:51 2024-07-25 13:31:51 2024-07-27 03:48:48 0000-00-00 00:00:00 2023 0 0 Soavtorji: Katja Goricar, Branka Strazisar, Nikola Besic, Vita Dolzan; str. 111-120, XII no. 1 Vol. 57 2023 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 2023-01-01 617-089:616-009.7 1318-2099 10.2478/raon-2023-0003 146440963 https://www.radioloncol.com/index.php/ro/article/view/3995/5144 1 beefaafc-4a68-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27492 RAZ_Vidic_Zala_2023.pdf RAZ_Vidic_Zala_2023.pdf 1 D69681ECC149E533E04F7A38AB105032 c67aef93ef79763550aed189c80ae758fa95f2c3b681e3eeda711cf10b533936 e1711787-4a68-11ef-b487-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=27494 Onkološki inštitut Ljubljana 0 0 0