Correlation of CYP2B6 , CYP2C19 , ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients
Abstract CYP2B6 , CYP2C19 , ABCC4 , and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse....
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| Veröffentlicht in: | Leukemia research 2012-01, Vol.36 (1), p.59-66 |
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| container_title | Leukemia research |
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| creator | Black, John L Litzow, Mark R Hogan, William J O’Kane, Dennis J Walker, Denise L Lesnick, Timothy G Kremers, Walter K Avula, Rajeswari Ketterling, Rhett P |
| description | Abstract CYP2B6 , CYP2C19 , ABCC4 , and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan–Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function. |
| doi_str_mv | 10.1016/j.leukres.2011.06.020 |
| format | Article |
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CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan–Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.</description><identifier>ISSN: 0145-2126</identifier><identifier>EISSN: 1873-5835</identifier><identifier>DOI: 10.1016/j.leukres.2011.06.020</identifier><identifier>PMID: 21741706</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>ABCC4 ; Adolescent ; Adult ; Aryl Hydrocarbon Hydroxylases - genetics ; Blood or marrow transplantation ; Blood Transfusion - methods ; Bone Marrow Transplantation - methods ; Child ; Child, Preschool ; Cyclophosphamide ; CYP2B6 ; CYP2C19 ; Cytochrome P-450 CYP2B6 ; Cytochrome P-450 CYP2C19 ; Female ; Gene Frequency ; Genetic Association Studies ; Genotype ; Hematology, Oncology and Palliative Medicine ; Humans ; Infant ; Leukemia - diagnosis ; Leukemia - genetics ; Leukemia - therapy ; Male ; Middle Aged ; Multidrug Resistance-Associated Proteins - genetics ; Oxidoreductases, N-Demethylating - genetics ; Polymorphism, Single Nucleotide - physiology ; Prognosis ; SOD2 ; Superoxide Dismutase - genetics ; Transplantation, Homologous ; Treatment Outcome ; Young Adult</subject><ispartof>Leukemia research, 2012-01, Vol.36 (1), p.59-66</ispartof><rights>Elsevier Ltd</rights><rights>2011 Elsevier Ltd</rights><rights>Copyright © 2011 Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-3b1de075fff3ecdd7981886d24feee54de6a66601d452dcb05fecd31566e37853</citedby><cites>FETCH-LOGICAL-c451t-3b1de075fff3ecdd7981886d24feee54de6a66601d452dcb05fecd31566e37853</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.leukres.2011.06.020$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21741706$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Black, John L</creatorcontrib><creatorcontrib>Litzow, Mark R</creatorcontrib><creatorcontrib>Hogan, William J</creatorcontrib><creatorcontrib>O’Kane, Dennis J</creatorcontrib><creatorcontrib>Walker, Denise L</creatorcontrib><creatorcontrib>Lesnick, Timothy G</creatorcontrib><creatorcontrib>Kremers, Walter K</creatorcontrib><creatorcontrib>Avula, Rajeswari</creatorcontrib><creatorcontrib>Ketterling, Rhett P</creatorcontrib><title>Correlation of CYP2B6 , CYP2C19 , ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients</title><title>Leukemia research</title><addtitle>Leuk Res</addtitle><description>Abstract CYP2B6 , CYP2C19 , ABCC4 , and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan–Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.</description><subject>ABCC4</subject><subject>Adolescent</subject><subject>Adult</subject><subject>Aryl Hydrocarbon Hydroxylases - genetics</subject><subject>Blood or marrow transplantation</subject><subject>Blood Transfusion - methods</subject><subject>Bone Marrow Transplantation - methods</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cyclophosphamide</subject><subject>CYP2B6</subject><subject>CYP2C19</subject><subject>Cytochrome P-450 CYP2B6</subject><subject>Cytochrome P-450 CYP2C19</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic Association Studies</subject><subject>Genotype</subject><subject>Hematology, Oncology and Palliative Medicine</subject><subject>Humans</subject><subject>Infant</subject><subject>Leukemia - diagnosis</subject><subject>Leukemia - genetics</subject><subject>Leukemia - therapy</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Multidrug Resistance-Associated Proteins - genetics</subject><subject>Oxidoreductases, N-Demethylating - genetics</subject><subject>Polymorphism, Single Nucleotide - physiology</subject><subject>Prognosis</subject><subject>SOD2</subject><subject>Superoxide Dismutase - genetics</subject><subject>Transplantation, Homologous</subject><subject>Treatment Outcome</subject><subject>Young Adult</subject><issn>0145-2126</issn><issn>1873-5835</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9v1DAQxS0EotvCRwD5xoUEj2M7yQXUhvJHqlSkwoGTlbUn4G02DrZDtXx6vN2FAxdOHsnvzZv5DSHPgJXAQL3alCMutwFjyRlAyVTJOHtAVtDUVSGbSj4kKwZCFhy4OiGnMW4YY7KF9jE54VALqJlakV-dDwHHPjk_UT_Q7usnfqHoy_uigzZX5xddJ2g_WXpz_ZbTbzj5tJuR3rn0nfolGb_FSN1E-3H0-RedoevRe3vv2fYh-DuaQj_FeeynROcchlOKT8ijoR8jPj2-Z-TLu8vP3Yfi6vr9x-78qjBCQiqqNVhktRyGoUJjbd020DTKcjEgohQWVa-UYmCF5NasmRyyrAKpFFZ1I6sz8uLQdw7-x4Ix6a2LBsc8DPol6hakaEUtRFbKg9IEH2PAQc_B5QV2GpjeU9cbfaSu99Q1UzpTz77nx4RlvUX71_UHcxa8OQgw7_nTYdDRZAYGrQtokrbe_Tfi9T8dzOgmZ_rxFncYN34JU4aoQUeumb7Zn35_eQDGKiZl9Rulzamr</recordid><startdate>20120101</startdate><enddate>20120101</enddate><creator>Black, John L</creator><creator>Litzow, Mark R</creator><creator>Hogan, William J</creator><creator>O’Kane, Dennis J</creator><creator>Walker, Denise L</creator><creator>Lesnick, Timothy G</creator><creator>Kremers, Walter K</creator><creator>Avula, Rajeswari</creator><creator>Ketterling, Rhett P</creator><general>Elsevier Ltd</general><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>7T5</scope><scope>H94</scope></search><sort><creationdate>20120101</creationdate><title>Correlation of CYP2B6 , CYP2C19 , ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients</title><author>Black, John L ; Litzow, Mark R ; Hogan, William J ; O’Kane, Dennis J ; Walker, Denise L ; Lesnick, Timothy G ; Kremers, Walter K ; Avula, Rajeswari ; Ketterling, Rhett P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-3b1de075fff3ecdd7981886d24feee54de6a66601d452dcb05fecd31566e37853</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>ABCC4</topic><topic>Adolescent</topic><topic>Adult</topic><topic>Aryl Hydrocarbon Hydroxylases - genetics</topic><topic>Blood or marrow transplantation</topic><topic>Blood Transfusion - methods</topic><topic>Bone Marrow Transplantation - methods</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Cyclophosphamide</topic><topic>CYP2B6</topic><topic>CYP2C19</topic><topic>Cytochrome P-450 CYP2B6</topic><topic>Cytochrome P-450 CYP2C19</topic><topic>Female</topic><topic>Gene Frequency</topic><topic>Genetic Association Studies</topic><topic>Genotype</topic><topic>Hematology, Oncology and Palliative Medicine</topic><topic>Humans</topic><topic>Infant</topic><topic>Leukemia - diagnosis</topic><topic>Leukemia - genetics</topic><topic>Leukemia - therapy</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Multidrug Resistance-Associated Proteins - genetics</topic><topic>Oxidoreductases, N-Demethylating - genetics</topic><topic>Polymorphism, Single Nucleotide - physiology</topic><topic>Prognosis</topic><topic>SOD2</topic><topic>Superoxide Dismutase - genetics</topic><topic>Transplantation, Homologous</topic><topic>Treatment Outcome</topic><topic>Young Adult</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Black, John L</creatorcontrib><creatorcontrib>Litzow, Mark R</creatorcontrib><creatorcontrib>Hogan, William J</creatorcontrib><creatorcontrib>O’Kane, Dennis J</creatorcontrib><creatorcontrib>Walker, Denise L</creatorcontrib><creatorcontrib>Lesnick, Timothy G</creatorcontrib><creatorcontrib>Kremers, Walter K</creatorcontrib><creatorcontrib>Avula, Rajeswari</creatorcontrib><creatorcontrib>Ketterling, Rhett P</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><jtitle>Leukemia research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Black, John L</au><au>Litzow, Mark R</au><au>Hogan, William J</au><au>O’Kane, Dennis J</au><au>Walker, Denise L</au><au>Lesnick, Timothy G</au><au>Kremers, Walter K</au><au>Avula, Rajeswari</au><au>Ketterling, Rhett P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correlation of CYP2B6 , CYP2C19 , ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients</atitle><jtitle>Leukemia research</jtitle><addtitle>Leuk Res</addtitle><date>2012-01-01</date><risdate>2012</risdate><volume>36</volume><issue>1</issue><spage>59</spage><epage>66</epage><pages>59-66</pages><issn>0145-2126</issn><eissn>1873-5835</eissn><abstract>Abstract CYP2B6 , CYP2C19 , ABCC4 , and SOD2 have been implicated in adverse drug reactions and survival after cyclophosphamide (CPA) treatment. 110 BMT patients who received high dose CPA treatment were genotyped for variants in these genes and the results were correlated with toxicity and relapse. CYP2B6 genotype significantly influenced overall toxicity suggesting active CYP2B6 alleles led to higher rates of overall toxicity. The p.R487C deficiency allele was significantly associated with a lower rate of overall toxicity and a higher rate of relapse. SOD2 rs4880 V16A polymorphism was associated with significantly less CPA-related overall toxicity and significantly lower relapse rates by Kaplan–Meier analysis although the SOD2 finding regarding relapse was not significant when evaluated by the cumulative incidence function.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>21741706</pmid><doi>10.1016/j.leukres.2011.06.020</doi><tpages>8</tpages></addata></record> |
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| subjects | ABCC4 Adolescent Adult Aryl Hydrocarbon Hydroxylases - genetics Blood or marrow transplantation Blood Transfusion - methods Bone Marrow Transplantation - methods Child Child, Preschool Cyclophosphamide CYP2B6 CYP2C19 Cytochrome P-450 CYP2B6 Cytochrome P-450 CYP2C19 Female Gene Frequency Genetic Association Studies Genotype Hematology, Oncology and Palliative Medicine Humans Infant Leukemia - diagnosis Leukemia - genetics Leukemia - therapy Male Middle Aged Multidrug Resistance-Associated Proteins - genetics Oxidoreductases, N-Demethylating - genetics Polymorphism, Single Nucleotide - physiology Prognosis SOD2 Superoxide Dismutase - genetics Transplantation, Homologous Treatment Outcome Young Adult |
| title | Correlation of CYP2B6 , CYP2C19 , ABCC4 and SOD2 genotype with outcomes in allogeneic blood and marrow transplant patients |
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