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rdf:type |
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lifeskim:mentions |
umls-concept:C0012899,
umls-concept:C0038952,
umls-concept:C0079744,
umls-concept:C0085862,
umls-concept:C0314603,
umls-concept:C0441712,
umls-concept:C1167395,
umls-concept:C1299583,
umls-concept:C1549571,
umls-concept:C1608386,
umls-concept:C1706907,
umls-concept:C2698872
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pubmed:issue |
8
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pubmed:dateCreated |
2011-2-25
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pubmed:abstractText |
Several drugs used for diffuse large B-cell lymphoma (DLBCL) treatment rely on DNA damage for tumor cell killing. We verified the prognostic impact of the host DNA repair genotype in 2 independent cohorts of DLBCL treated with R-CHOP21 (training cohort, 163 cases; validation cohort, 145 cases). Among 35 single nucleotide polymorphisms analyzed in the training series, MLH1 rs1799977 was the sole predicting overall survival. DLBCL carrying the MLH1 AG/GG genotype displayed an increased death risk (hazard ratio [HR] = 3.23; P < .001; q =0 .009) compared with patients carrying the AA genotype. Multivariate analysis adjusted for International Prognostic Index identified MLH1 AG/GG as an independent OS predictor (P < .001). The poor prognosis of MLH1 AG/GG was the result of an increased risk of failing both R-CHOP21 (HR = 2.02; P = .007) and platinum-based second-line (HR = 2.26; P = .044) treatment. Survival analysis in the validation series confirmed all outcomes predicted by MLH1 rs1799977. The effect on OS of MLH1, a component of the DNA mismatch repair system, is consistent with its role in regulating the genotoxic effects of doxorubicin and platinum compounds, which are a mainstay of DLBCL first- and second-line treatment.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1528-0020
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pubmed:author |
pubmed-author:BrunaRiccardoR,
pubmed-author:BruscagginAlessioA,
pubmed-author:CapelloDanielaD,
pubmed-author:CarboneAntoninoA,
pubmed-author:ChiappellaAnnalisaA,
pubmed-author:De PaoliLorenzoL,
pubmed-author:Di RoccoAliceA,
pubmed-author:FabbriAlbertoA,
pubmed-author:FangazioMarcoM,
pubmed-author:FoàRobinR,
pubmed-author:ForconiFrancescoF,
pubmed-author:FranceschettiSilviaS,
pubmed-author:GaidanoGianlucaG,
pubmed-author:GiacheliaManuelaM,
pubmed-author:GloghiniAnnunziataA,
pubmed-author:HohausStefanS,
pubmed-author:LadettoMarcoM,
pubmed-author:LauriaFrancescoF,
pubmed-author:Lobetti BodoniChiaraC,
pubmed-author:MartelliMaurizioM,
pubmed-author:PoglianiEnrico MEM,
pubmed-author:RasiSilviaS,
pubmed-author:RossiDavideD,
pubmed-author:TisiMaria ChiaraMC,
pubmed-author:VitoloUmbertoU
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pubmed:issnType |
Electronic
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pubmed:day |
24
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2405-13
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pubmed:meshHeading |
pubmed-meshheading:21156845-Adaptor Proteins, Signal Transducing,
pubmed-meshheading:21156845-Antineoplastic Combined Chemotherapy Protocols,
pubmed-meshheading:21156845-Artificial Intelligence,
pubmed-meshheading:21156845-Cyclophosphamide,
pubmed-meshheading:21156845-DNA Repair,
pubmed-meshheading:21156845-Doxorubicin,
pubmed-meshheading:21156845-Genotype,
pubmed-meshheading:21156845-Humans,
pubmed-meshheading:21156845-Individualized Medicine,
pubmed-meshheading:21156845-Lymphoma, Large B-Cell, Diffuse,
pubmed-meshheading:21156845-Nuclear Proteins,
pubmed-meshheading:21156845-Pharmacogenetics,
pubmed-meshheading:21156845-Platinum Compounds,
pubmed-meshheading:21156845-Polymorphism, Single Nucleotide,
pubmed-meshheading:21156845-Predictive Value of Tests,
pubmed-meshheading:21156845-Prednisone,
pubmed-meshheading:21156845-Prognosis,
pubmed-meshheading:21156845-Risk Assessment,
pubmed-meshheading:21156845-Survival Rate,
pubmed-meshheading:21156845-Vincristine
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pubmed:year |
2011
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pubmed:articleTitle |
The host genetic background of DNA repair mechanisms is an independent predictor of survival in diffuse large B-cell lymphoma.
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pubmed:affiliation |
Division of Hematology, Department of Clinical and Experimental Medicine & CRIFF, Amedeo Avogadro University of Eastern Piedmont, Via Solaroli 17, 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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