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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2009-6-10
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pubmed:abstractText |
Knowledge on the impact of pharmacogenetics in predicting outcome and toxicity in diffuse large B-cell lymphoma (DLBCL) is scant. We tested 106 consecutive DLBCL treated with R-CHOP21 for 19 single nucleotide polymorphisms (SNPs) from 15 genes potentially relevant to rituximab-CHOP (R-CHOP) pharmacogenetics. Associations of SNPs with event-free survival (EFS) and toxicity were controlled for multiple testing. Genotypic variants of nicotinamide adenine dinucleotide phosphate (NAD(P)H) oxidase p22phox (CYBA rs4673) and alpha1 class glutathione S-transferase (GSTA1 rs3957357) were independent predictors of EFS (CYBA rs4673 TT genotype: HR 2.06, P=0.038; GSTA1 rs3957357 CT/TT genotypes: HR 0.38, P=0.003), after adjusting for International Prognostic Index (IPI). CYBA rs4673 and GSTA1 rs3957357 also predicted outcome in DLBCL subgroups by IPI. Impact of SNPs on toxicity was evaluated in 658 R-CHOP21 courses utilizing generalized estimating equations. NCF4 rs1883112 was an independent predictor against hematologic (odds ratios (OR): 0.45; P=0.018), infectious (OR: 0.46; P=0.003) and cardiac toxicity (OR: 0.37; P=0.023). Overall, host SNPs affecting doxorubicin pharmacodynamics (CYBA rs4673) and alkylator detoxification (GSTA1 rs3957357) may predict outcome in R-CHOP21-treated DLBCL. Also, NCF4 rs1883112, a SNP of NAD(P)H oxidase p40phox, may have a function in protecting against hematologic and nonhematologic toxicity. These results highlight the need to improve characterization of the host genetic background for a better prognostication of DLBCL.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal,
http://linkedlifedata.com/resource/pubmed/chemical/Antibodies, Monoclonal...,
http://linkedlifedata.com/resource/pubmed/chemical/CYBA protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophosphamide,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/GSTA1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Prednisone,
http://linkedlifedata.com/resource/pubmed/chemical/Vincristine,
http://linkedlifedata.com/resource/pubmed/chemical/rituximab
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
1476-5551
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pubmed:author |
pubmed-author:BertoniFF,
pubmed-author:CapelleJJ,
pubmed-author:CastelliAA,
pubmed-author:ChiappellaAA,
pubmed-author:ConconiAA,
pubmed-author:De PaolaDD,
pubmed-author:FranceschettiSS,
pubmed-author:GaidanoGG,
pubmed-author:KweeII,
pubmed-author:PoglianiE MEM,
pubmed-author:RamponiAA,
pubmed-author:RastFF,
pubmed-author:RossiDD,
pubmed-author:VitoloUU
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pubmed:issnType |
Electronic
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1118-26
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:19448608-Aged,
pubmed-meshheading:19448608-Antibodies, Monoclonal,
pubmed-meshheading:19448608-Antibodies, Monoclonal, Murine-Derived,
pubmed-meshheading:19448608-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:19448608-Cyclophosphamide,
pubmed-meshheading:19448608-Disease-Free Survival,
pubmed-meshheading:19448608-Doxorubicin,
pubmed-meshheading:19448608-Drug Toxicity,
pubmed-meshheading:19448608-Female,
pubmed-meshheading:19448608-Genotype,
pubmed-meshheading:19448608-Glutathione Transferase,
pubmed-meshheading:19448608-Humans,
pubmed-meshheading:19448608-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:19448608-Male,
pubmed-meshheading:19448608-Middle Aged,
pubmed-meshheading:19448608-NADPH Oxidase,
pubmed-meshheading:19448608-Pharmacogenetics,
pubmed-meshheading:19448608-Polymorphism, Single Nucleotide,
pubmed-meshheading:19448608-Predictive Value of Tests,
pubmed-meshheading:19448608-Prednisone,
pubmed-meshheading:19448608-Prognosis,
pubmed-meshheading:19448608-Vincristine
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pubmed:year |
2009
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pubmed:articleTitle |
Analysis of the host pharmacogenetic background for prediction of outcome and toxicity in diffuse large B-cell lymphoma treated with R-CHOP21.
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pubmed:affiliation |
Division of Hematology, Department of Clinical and Experimental Medicine and BRMA, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy. rossidav@med.unipmn.it
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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