{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T17:55:51Z","timestamp":1780422951011,"version":"3.54.1"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Thalidomide is commonly used in treatment of multiple myeloma (<jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>). This study aimed to analyse the influence of clinical and molecular factors \u2010 single nucleotide polymorphisms (<jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s) of the <jats:italic><jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content><\/jats:italic> gene: rs6768972 and rs1672753, on the risk of adverse effects (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) of thalidomide\u2010based chemotherapy in patients with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>. The study group included 82 patients receiving <jats:styled-content style=\"fixed-case\">CTD<\/jats:styled-content> (thalidomide, cyclophosphamide, dexamethasone) as first line treatment. The intensity of haematological and non\u2010haematological <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s was assessed according to the Common Terminology Criteria for Adverse Events v4.03. Multivariate analysis showed that patients with the <jats:italic><jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> genotype (rs1672753) had more than a 14\u2010fold higher risk of peripheral polyneuropathy compared to patients with other variants of the investigated <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content> [odds ratio (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>)\u00a0=\u00a014\u00b729]. Carriers of this genotype were burdened with significantly (about 17\u2010fold) higher risk of diarrhoea during treatment (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a016\u00b767). The presence of <jats:italic><jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">AA<\/jats:styled-content> (rs6768972) or <jats:styled-content style=\"fixed-case\">TT<\/jats:styled-content> (rs1672753) genotypes was associated with about 333\u2010fold and 250\u2010fold lower risk of constipation in the course of therapy (<jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a00\u00b7003; <jats:styled-content style=\"fixed-case\">OR<\/jats:styled-content>\u00a0=\u00a00\u00b7004, respectively). Selected <jats:italic><jats:styled-content style=\"fixed-case\">CRBN<\/jats:styled-content><\/jats:italic> <jats:styled-content style=\"fixed-case\">SNP<\/jats:styled-content>s may be useful in assessing the probability of <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s in the form of peripheral polyneuropathy and gastrointestinal motility disorders associated with the use of thalidomide in patients with <jats:styled-content style=\"fixed-case\">MM<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/bjh.15972","type":"journal-article","created":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T09:41:37Z","timestamp":1558518097000},"page":"695-705","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Polymorphisms in the promotor region of the <i><scp>CRBN<\/scp><\/i> gene as a predictive factor for peripheral neuropathy in the course of thalidomide\u2010based chemotherapy in multiple myeloma patients"],"prefix":"10.1111","volume":"186","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7399-8340","authenticated-orcid":false,"given":"Rados\u0142aw","family":"Mlak","sequence":"first","affiliation":[{"name":"Department of Human Physiology Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2352-394X","authenticated-orcid":false,"given":"Aneta","family":"Szudy\u2010Szczyrek","sequence":"additional","affiliation":[{"name":"Department of Haemato\u2010oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcin","family":"Mazurek","sequence":"additional","affiliation":[{"name":"Department of Human Physiology Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Szczyrek","sequence":"additional","affiliation":[{"name":"Department of Pneumonology, Oncology and Allergology Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwona","family":"Homa\u2010Mlak","sequence":"additional","affiliation":[{"name":"Department of Human Physiology Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micha\u0142","family":"Mielnik","sequence":"additional","affiliation":[{"name":"Department of Haemato\u2010oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylwia","family":"Chocholska","sequence":"additional","affiliation":[{"name":"Department of Haemato\u2010oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Jankowska\u2010\u0141\u0119cka","sequence":"additional","affiliation":[{"name":"Department of Haemato\u2010oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Ma\u0142ecka\u2010Massalska","sequence":"additional","affiliation":[{"name":"Department of Human Physiology Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marek","family":"Hus","sequence":"additional","affiliation":[{"name":"Department of Haemato\u2010oncology and Bone Marrow Transplantation Medical University of Lublin Lublin Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2011.03.024"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdh300"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.19502.x"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.thj.6200115"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2015.10.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00005-016-0442-6"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000037480.59194.85"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70068-1"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197509)36:3<842::AID-CNCR2820360303>3.0.CO;2-U"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2013.099358"},{"key":"e_1_2_8_12_1","unstructured":"FDA. (2006).Thalidomide (marketed as Thalomid) Information[WWW Document]. Available at:https:\/\/www.fda.gov\/Drugs\/DrugSafety\/PostmarketDrugSafetyInformationforPatientsandProviders\/ucm107296.htm(Accessed: 5 March 2019)."},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1751-553X.2007.00948.x"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hon.2337"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdf213"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12032-009-9262-4"},{"key":"e_1_2_8_17_1","first-page":"194","article-title":"Management of thalidomide toxicity","volume":"1","author":"Ghobrial I.M.","year":"2003","journal-title":"The Journal of Supportive Oncology"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.04.242"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-014-2063-7"},{"key":"e_1_2_8_20_1","doi-asserted-by":"crossref","first-page":"3628","DOI":"10.1182\/blood.V124.21.3628.3628","article-title":"Cereblon (CRBN) gene polymorphisms predict clinical response and progression\u2010free survival in multiple myeloma patients treated with lenalidomide: a pharmacogenetic study of immense consortium","volume":"124","author":"Iskierka\u2010Jazdzewska E.","year":"2014","journal-title":"Blood"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.28.0792"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-016-2743-6"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2002.tb00184.x"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.313"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.4065\/78.1.21"},{"key":"e_1_2_8_26_1","first-page":"233","article-title":"Anemia in multiple myeloma","volume":"2","author":"Ludwig H.","year":"2004","journal-title":"Clinical Advances in Hematology & Oncology: H&O"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-018-0040-1"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.05.6689"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.012674"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2015.83"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-338665"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2011.043372"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-11-568923"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00238.x"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3109\/10428194.2011.555027"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000421-198212000-00014"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.067058"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1080\/10428190601001904"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.1853"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(14)70442-5"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.4065\/79.7.875"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2013.59"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21387"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.2165\/00063030-200115030-00003"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199911183412102"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.2174\/156800906777441762"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.25307"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2004.00382.x"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2008.01121.x"},{"key":"e_1_2_8_50_1","first-page":"942","article-title":"Long\u2010 term outcome of thalidomide and cyclosporine in patients with IPSS low\/intermediate\u2010 1 myelodysplastic syndromes","volume":"36","author":"Wang J.","year":"2015","journal-title":"Zhonghua xue ye xue za zhi = Zhonghua Xueyexue Zazhi"}],"container-title":["British Journal of Haematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15972","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/bjh.15972","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bjh.15972","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T05:35:26Z","timestamp":1694324126000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bjh.15972"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,22]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2019,9]]}},"alternative-id":["10.1111\/bjh.15972"],"URL":"https:\/\/doi.org\/10.1111\/bjh.15972","archive":["Portico"],"relation":{},"ISSN":["0007-1048","1365-2141"],"issn-type":[{"value":"0007-1048","type":"print"},{"value":"1365-2141","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,22]]},"assertion":[{"value":"2019-02-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-05-22","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}