Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes
Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently ident...
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| Veröffentlicht in: | Clinical pharmacology and therapeutics 2019-02, Vol.105 (2), p.402-410 |
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| creator | Wright, Galen E.B. Amstutz, Ursula Drögemöller, Britt I. Shih, Joanne Rassekh, Shahrad R. Hayden, Michael R. Carleton, Bruce C. Ross, Colin J.D. Visscher, Henk Aminkeng, Folefac Higginson, Michelle Massah, Nasim Miao, Fudan Bhavsar, Amit Lee, Jong Bendyshe‐Walton, Tessa Tanoshima, Reo Johnson, David Zhuwaki, Carnation Honcharik, Nick Jong, Geert‘t Israels, Sara Staub, Michelle Rieder, Michael Faught, Lauren Ito, Shinya Nathan, Paul Karande, Smita Vaillancourt, Régis Johnston, Donna Nguyen, Kimmy Bussières, Jean‐François Lebel, Denis Jean‐Louis, Jennifer |
| description | Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently identified risk variant, CEP72 rs924607, and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP72 rs924607 was significantly associated with VIPN (P = 0.02; odds ratio (OR) = 3.4). ADME analyses identified associations between VIPN and ABCC1 rs3784867 (P = 5.34 × 10−5; OR = 4.9), and SLC5A7 rs1013940 (P = 9.00 × 10−4; OR= 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10−4; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN. |
| doi_str_mv | 10.1002/cpt.1179 |
| format | Article |
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Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently identified risk variant, CEP72 rs924607, and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP72 rs924607 was significantly associated with VIPN (P = 0.02; odds ratio (OR) = 3.4). ADME analyses identified associations between VIPN and ABCC1 rs3784867 (P = 5.34 × 10−5; OR = 4.9), and SLC5A7 rs1013940 (P = 9.00 × 10−4; OR= 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10−4; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN.</description><identifier>ISSN: 0009-9236</identifier><identifier>EISSN: 1532-6535</identifier><identifier>DOI: 10.1002/cpt.1179</identifier><identifier>PMID: 29999516</identifier><language>eng</language><publisher>United States: John Wiley and Sons Inc</publisher><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics ; Antineoplastic Agents, Phytogenic - toxicity ; Child ; Child, Preschool ; Computational Biology ; Female ; Humans ; Male ; Microtubule-Associated Proteins - genetics ; Multidrug Resistance-Associated Proteins - genetics ; Peripheral Nervous System Diseases - chemically induced ; Peripheral Nervous System Diseases - genetics ; Pharmacogenetics ; Tissue Distribution ; Vincristine - pharmacokinetics ; Vincristine - toxicity</subject><ispartof>Clinical pharmacology and therapeutics, 2019-02, Vol.105 (2), p.402-410</ispartof><rights>2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics</rights><rights>2018 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4109-b700b8f4178d3a7f3f159ed124dd0c0b1055b03d6e99c290f411acdae7d365053</citedby><cites>FETCH-LOGICAL-c4109-b700b8f4178d3a7f3f159ed124dd0c0b1055b03d6e99c290f411acdae7d365053</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcpt.1179$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcpt.1179$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29999516$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wright, Galen E.B.</creatorcontrib><creatorcontrib>Amstutz, Ursula</creatorcontrib><creatorcontrib>Drögemöller, Britt I.</creatorcontrib><creatorcontrib>Shih, Joanne</creatorcontrib><creatorcontrib>Rassekh, Shahrad R.</creatorcontrib><creatorcontrib>Hayden, Michael R.</creatorcontrib><creatorcontrib>Carleton, Bruce C.</creatorcontrib><creatorcontrib>Ross, Colin J.D.</creatorcontrib><creatorcontrib>Visscher, Henk</creatorcontrib><creatorcontrib>Aminkeng, Folefac</creatorcontrib><creatorcontrib>Higginson, Michelle</creatorcontrib><creatorcontrib>Massah, Nasim</creatorcontrib><creatorcontrib>Miao, Fudan</creatorcontrib><creatorcontrib>Bhavsar, Amit</creatorcontrib><creatorcontrib>Lee, Jong</creatorcontrib><creatorcontrib>Bendyshe‐Walton, Tessa</creatorcontrib><creatorcontrib>Tanoshima, Reo</creatorcontrib><creatorcontrib>Johnson, David</creatorcontrib><creatorcontrib>Zhuwaki, Carnation</creatorcontrib><creatorcontrib>Honcharik, Nick</creatorcontrib><creatorcontrib>Jong, Geert‘t</creatorcontrib><creatorcontrib>Israels, Sara</creatorcontrib><creatorcontrib>Staub, Michelle</creatorcontrib><creatorcontrib>Rieder, Michael</creatorcontrib><creatorcontrib>Faught, Lauren</creatorcontrib><creatorcontrib>Ito, Shinya</creatorcontrib><creatorcontrib>Nathan, Paul</creatorcontrib><creatorcontrib>Karande, Smita</creatorcontrib><creatorcontrib>Vaillancourt, Régis</creatorcontrib><creatorcontrib>Johnston, Donna</creatorcontrib><creatorcontrib>Nguyen, Kimmy</creatorcontrib><creatorcontrib>Bussières, Jean‐François</creatorcontrib><creatorcontrib>Lebel, Denis</creatorcontrib><creatorcontrib>Jean‐Louis, Jennifer</creatorcontrib><creatorcontrib>Canadian Pharmacogenomics Network for Drug Safety Consortium</creatorcontrib><creatorcontrib>The Canadian Pharmacogenomics Network for Drug Safety Consortium</creatorcontrib><title>Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes</title><title>Clinical pharmacology and therapeutics</title><addtitle>Clin Pharmacol Ther</addtitle><description>Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently identified risk variant, CEP72 rs924607, and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP72 rs924607 was significantly associated with VIPN (P = 0.02; odds ratio (OR) = 3.4). ADME analyses identified associations between VIPN and ABCC1 rs3784867 (P = 5.34 × 10−5; OR = 4.9), and SLC5A7 rs1013940 (P = 9.00 × 10−4; OR= 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10−4; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN.</description><subject>Antineoplastic Agents, Phytogenic - pharmacokinetics</subject><subject>Antineoplastic Agents, Phytogenic - toxicity</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Computational Biology</subject><subject>Female</subject><subject>Humans</subject><subject>Male</subject><subject>Microtubule-Associated Proteins - genetics</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Peripheral Nervous System Diseases - chemically induced</subject><subject>Peripheral Nervous System Diseases - genetics</subject><subject>Pharmacogenetics</subject><subject>Tissue Distribution</subject><subject>Vincristine - pharmacokinetics</subject><subject>Vincristine - toxicity</subject><issn>0009-9236</issn><issn>1532-6535</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>EIF</sourceid><recordid>eNp1kctO3DAUhi1EBVNA4glQlmwCx0mcxBukasRlJNTOAthajn3CuE3s1E5As-sj9Bl5kpqrpgu8sSx__-dj_YQcUjihANmpGsYTSiu-RWaU5VlaspxtkxkA8JRneblLvobwMx4LXtc7ZDfjcTFazsh6uZK-l8rdo3W9USFxbXJnrPImjMbi05-_C6snhTpZojfDCr3sku84eTfIcbVOFv3QGSVHDMm76lfMjUYl0upkYWPCjDG-kblEi2GffGllF_Dgbd8jtxfnN_Or9PrH5WL-7TpVBY3jNxVAU7cFrWqdy6rNW8o4apoVWoOChgJjDeS6RM5VxiGSVCotsdJ5yYDle-Ts1TtMTY9aoR3jF8TgTS_9WjhpxP831qzEvXsQJaMciiIKjt8E3v2eMIyiN0Fh10mLbgoig7LmGas2UeVdCB7bj2coiOemRGxKPDcV0aPNsT7A92oikL4Cj6bD9aciMV_evAj_ARD3ods</recordid><startdate>201902</startdate><enddate>201902</enddate><creator>Wright, Galen E.B.</creator><creator>Amstutz, Ursula</creator><creator>Drögemöller, Britt I.</creator><creator>Shih, Joanne</creator><creator>Rassekh, Shahrad R.</creator><creator>Hayden, Michael R.</creator><creator>Carleton, Bruce C.</creator><creator>Ross, Colin J.D.</creator><creator>Visscher, Henk</creator><creator>Aminkeng, Folefac</creator><creator>Higginson, Michelle</creator><creator>Massah, Nasim</creator><creator>Miao, Fudan</creator><creator>Bhavsar, Amit</creator><creator>Lee, Jong</creator><creator>Bendyshe‐Walton, Tessa</creator><creator>Tanoshima, Reo</creator><creator>Johnson, David</creator><creator>Zhuwaki, Carnation</creator><creator>Honcharik, Nick</creator><creator>Jong, Geert‘t</creator><creator>Israels, Sara</creator><creator>Staub, Michelle</creator><creator>Rieder, Michael</creator><creator>Faught, Lauren</creator><creator>Ito, Shinya</creator><creator>Nathan, Paul</creator><creator>Karande, Smita</creator><creator>Vaillancourt, Régis</creator><creator>Johnston, Donna</creator><creator>Nguyen, Kimmy</creator><creator>Bussières, Jean‐François</creator><creator>Lebel, Denis</creator><creator>Jean‐Louis, Jennifer</creator><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>201902</creationdate><title>Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes</title><author>Wright, Galen E.B. ; Amstutz, Ursula ; Drögemöller, Britt I. ; Shih, Joanne ; Rassekh, Shahrad R. ; Hayden, Michael R. ; Carleton, Bruce C. ; Ross, Colin J.D. ; Visscher, Henk ; Aminkeng, Folefac ; Higginson, Michelle ; Massah, Nasim ; Miao, Fudan ; Bhavsar, Amit ; Lee, Jong ; Bendyshe‐Walton, Tessa ; Tanoshima, Reo ; Johnson, David ; Zhuwaki, Carnation ; Honcharik, Nick ; Jong, Geert‘t ; Israels, Sara ; Staub, Michelle ; Rieder, Michael ; Faught, Lauren ; Ito, Shinya ; Nathan, Paul ; Karande, Smita ; Vaillancourt, Régis ; Johnston, Donna ; Nguyen, Kimmy ; Bussières, Jean‐François ; Lebel, Denis ; Jean‐Louis, Jennifer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4109-b700b8f4178d3a7f3f159ed124dd0c0b1055b03d6e99c290f411acdae7d365053</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>Antineoplastic Agents, Phytogenic - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical pharmacology and therapeutics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wright, Galen E.B.</au><au>Amstutz, Ursula</au><au>Drögemöller, Britt I.</au><au>Shih, Joanne</au><au>Rassekh, Shahrad R.</au><au>Hayden, Michael R.</au><au>Carleton, Bruce C.</au><au>Ross, Colin J.D.</au><au>Visscher, Henk</au><au>Aminkeng, Folefac</au><au>Higginson, Michelle</au><au>Massah, Nasim</au><au>Miao, Fudan</au><au>Bhavsar, Amit</au><au>Lee, Jong</au><au>Bendyshe‐Walton, Tessa</au><au>Tanoshima, Reo</au><au>Johnson, David</au><au>Zhuwaki, Carnation</au><au>Honcharik, Nick</au><au>Jong, Geert‘t</au><au>Israels, Sara</au><au>Staub, Michelle</au><au>Rieder, Michael</au><au>Faught, Lauren</au><au>Ito, Shinya</au><au>Nathan, Paul</au><au>Karande, Smita</au><au>Vaillancourt, Régis</au><au>Johnston, Donna</au><au>Nguyen, Kimmy</au><au>Bussières, Jean‐François</au><au>Lebel, Denis</au><au>Jean‐Louis, Jennifer</au><aucorp>Canadian Pharmacogenomics Network for Drug Safety Consortium</aucorp><aucorp>The Canadian Pharmacogenomics Network for Drug Safety Consortium</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes</atitle><jtitle>Clinical pharmacology and therapeutics</jtitle><addtitle>Clin Pharmacol Ther</addtitle><date>2019-02</date><risdate>2019</risdate><volume>105</volume><issue>2</issue><spage>402</spage><epage>410</epage><pages>402-410</pages><issn>0009-9236</issn><eissn>1532-6535</eissn><abstract>Vincristine is an effective chemotherapeutic drug for various cancers, including acute lymphoblastic leukemia (ALL). Unfortunately, clinical utility is restricted by dose‐limiting vincristine‐induced peripheral neuropathies (VIPN). We sought to determine the association of VIPN with a recently identified risk variant, CEP72 rs924607, and drug absorption, distribution, metabolism, and excretion (ADME) gene variants in pediatric ALL. This was followed by a meta‐analysis of pharmacogenomic data from over 500 patients. CEP72 rs924607 was significantly associated with VIPN (P = 0.02; odds ratio (OR) = 3.4). ADME analyses identified associations between VIPN and ABCC1 rs3784867 (P = 5.34 × 10−5; OR = 4.9), and SLC5A7 rs1013940 (P = 9.00 × 10−4; OR= 8.6); genes involved in vincristine transport and inherited neuropathies, respectively. Meta‐analysis identified an association with a variant related to TTPA (rs10504361: P = 6.85 × 10−4; OR = 2.0), a heritable neuropathy‐related gene. This study provides essential corroboratory evidence for CEP72 rs924607 and highlights the importance of drug transporter and inherited neuropathy genes in VIPN.</abstract><cop>United States</cop><pub>John Wiley and Sons Inc</pub><pmid>29999516</pmid><doi>10.1002/cpt.1179</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Clinical pharmacology and therapeutics, 2019-02, Vol.105 (2), p.402-410 |
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| language | eng |
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| subjects | Antineoplastic Agents, Phytogenic - pharmacokinetics Antineoplastic Agents, Phytogenic - toxicity Child Child, Preschool Computational Biology Female Humans Male Microtubule-Associated Proteins - genetics Multidrug Resistance-Associated Proteins - genetics Peripheral Nervous System Diseases - chemically induced Peripheral Nervous System Diseases - genetics Pharmacogenetics Tissue Distribution Vincristine - pharmacokinetics Vincristine - toxicity |
| title | Pharmacogenomics of Vincristine‐Induced Peripheral Neuropathy Implicates Pharmacokinetic and Inherited Neuropathy Genes |
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