{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,9]],"date-time":"2026-08-09T16:43:05Z","timestamp":1786293785112,"version":"build-2736575974"},"reference-count":38,"publisher":"Walter de Gruyter GmbH","issue":"1","license":[{"start":{"date-parts":[[2023,3,1]],"date-time":"2023-03-01T00:00:00Z","timestamp":1677628800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,22]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"j_raon-2023-0003_s_008\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Tramadol is an opioid analgesic often used for pain management after breast cancer surgery. Its analgesic activity is due to the activation of the \u03bc-opioid receptor, encoded by the\n                      <jats:italic>OPRM1<\/jats:italic>\n                      gene. This study investigated the association of genetic variability in\n                      <jats:italic>OPRM1<\/jats:italic>\n                      and its regulatory miRNA genes with outcomes of tramadol\/paracetamol treatment after breast cancer surgery with axillary lymphadenectomy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_raon-2023-0003_s_009\">\n                    <jats:title>Patients and methods<\/jats:title>\n                    <jats:p>\n                      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\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs1799971 and rs677830,\n                      <jats:italic>MIR23B<\/jats:italic>\n                      rs1011784, and\n                      <jats:italic>MIR107<\/jats:italic>\n                      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\u2019s exact test, and Mann-Whitney test.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_raon-2023-0003_s_010\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The investigated\n                      <jats:italic>OPRM1<\/jats:italic>\n                      related polymorphisms were not associated with acute pain assessed with the VAS scale within four weeks after surgery (all P &gt; 0.05). Carriers of at least one polymorphic\n                      <jats:italic>OPRM1<\/jats:italic>\n                      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\u201312.64, P = 0.004). Carriers of at least one polymorphic\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs677830 allele had a higher risk of constipation after third week of tramadol treatment (OR = 3.11, 95% CI = 1.08\u20138.89, P = 0.035). Furthermore, carriers of two polymorphic\n                      <jats:italic>MIR23B<\/jats:italic>\n                      rs1011784 alleles had a higher risk of nausea after 28 days of tramadol treatment (OR = 7.35, 95% CI = 1.27\u201342.6, P = 0.026), while heterozygotes for\n                      <jats:italic>MIR107<\/jats:italic>\n                      rs2296616 allele had a lower risk of nausea after 21 days of tramadol treatment (OR = 0.21, 95% CI = 0.05\u20130.87, P = 0.031). In carriers of two polymorphic\n                      <jats:italic>MIR107<\/jats:italic>\n                      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\n                      <jats:italic>MIR23B<\/jats:italic>\n                      rs1011784 allele experienced more neuropathic pain after adjustment for tramadol dose (OR = 2.85, 95% CI = 1.07\u20137.59, P = 0.036), while carriers of at least one polymorphic\n                      <jats:italic>OPRM1<\/jats:italic>\n                      rs677830 allele experienced less neuropathic pain compared to carriers of two wild-type alleles (OR = 0.38, 95% CI = 0.15\u20130.99, P = 0.047).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"j_raon-2023-0003_s_011\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Genetic variability of\n                      <jats:italic>OPRM1<\/jats:italic>\n                      and genes coding for miRNAs that could affect\n                      <jats:italic>OPRM1<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.2478\/raon-2023-0003","type":"journal-article","created":{"date-parts":[[2023,3,21]],"date-time":"2023-03-21T07:19:12Z","timestamp":1679383152000},"page":"111-120","source":"Crossref","is-referenced-by-count":8,"title":["Association of\n                    <i>OPRM1<\/i>\n                    ,\n                    <i>MIR23B<\/i>\n                    , and\n                    <i>MIR107<\/i>\n                    genetic variability with acute pain, chronic pain and adverse effects after postoperative tramadol and paracetamol treatment in breast cancer"],"prefix":"10.2478","volume":"57","author":[{"given":"Zala","family":"Vidic","sequence":"first","affiliation":[{"name":"Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katja","family":"Goricar","sequence":"additional","affiliation":[{"name":"Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Strazisar","sequence":"additional","affiliation":[{"name":"Institute of Oncology , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikola","family":"Besic","sequence":"additional","affiliation":[{"name":"Institute of Oncology , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vita","family":"Dolzan","sequence":"additional","affiliation":[{"name":"Pharmacogenetics Laboratory, Institute of Biochemistry and Molecular Genetics, Faculty of Medicine, University of Ljubljana , Ljubljana , Slovenia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"374","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"2026080916205051032_j_raon-2023-0003_ref_001","doi-asserted-by":"crossref","unstructured":"Subedi M, Bajaj S, Kumar MS, Yc M. 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