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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

BACKGROUND: Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic 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 miRN...

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Autores principales: Vidic, Zala, Goricar, Katja, Strazisar, Branka, Besic, Nikola, Dolzan, Vita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Sciendo 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039478/
https://www.ncbi.nlm.nih.gov/pubmed/36942908
http://dx.doi.org/10.2478/raon-2023-0003
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author Vidic, Zala
Goricar, Katja
Strazisar, Branka
Besic, Nikola
Dolzan, Vita
author_facet Vidic, Zala
Goricar, Katja
Strazisar, Branka
Besic, Nikola
Dolzan, Vita
author_sort Vidic, Zala
collection PubMed
description BACKGROUND: Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic 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/paracetamol 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 genotyped 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 MIR23B rs1011784 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.
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spelling pubmed-100394782023-03-26 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 Vidic, Zala Goricar, Katja Strazisar, Branka Besic, Nikola Dolzan, Vita Radiol Oncol Research Article BACKGROUND: Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic 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/paracetamol 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 genotyped 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 MIR23B rs1011784 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. Sciendo 2023-03-22 /pmc/articles/PMC10039478/ /pubmed/36942908 http://dx.doi.org/10.2478/raon-2023-0003 Text en © 2023 Zala Vidic, Katja Goricar, Branka Strazisar, Nikola Besic, Vita Dolzan, published by Sciendo https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.
spellingShingle Research Article
Vidic, Zala
Goricar, Katja
Strazisar, Branka
Besic, Nikola
Dolzan, Vita
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
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10039478/
https://www.ncbi.nlm.nih.gov/pubmed/36942908
http://dx.doi.org/10.2478/raon-2023-0003
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