Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of pati...Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.展开更多
基金funded by the Associazione Giacomo Onlus 2012-2020(Castiglioncello,Italy)(to Mini E)Fondazione Cassa di Risparmio di Firenze-ref.no.2013.0842 and ref.no.2014.0969(Firenze,Italy)(to Nobili S).
文摘Aim:Diffuse large B-cell lymphoma(DLBCL)is the most common B-cell non-Hodgkin lymphoma(NHL).Despite the availability of clinical and molecular algorithms applied for the prediction of prognosis,in up to 30%-40%of patients,intrinsic or acquired drug resistance occurs.Constitutional genetics may help to predict R-CHOP resistance.This study aimed to validate previously identified single nucleotide polymorphisms(SNPs)in the literature as potential predictors of R-CHOP resistance in DLBCL patients,SNPs.Methods:Twenty SNPs,involved in R-CHOP pharmacokinetics/pharmacodynamics or other pathobiological processes,were investigated in 185 stage Ⅰ-Ⅳ DLBCL patients included in a multi-institution pharmacogenetic study to validate their previously identified correlations with resistance to R-CHOP.Results:Correlations between rs2010963(VEGFA gene)and sex(P=0.046),and rs1625895(TP53 gene)and stage(P=0.003)were shown.After multivariate analyses,a concordant effect(i.e.,increased risk of disease progression and death)was observed for rs1883112(NCF4 gene)and rs1800871(IL10 gene).When patients were grouped according to the revised International Prognostic Index(R-IPI),both these SNPs further discriminated progression-free survival(PFS)and overall survival(OS)of the R-IPI-1-2 subgroup.Overall,patients harboring the rare allele showed shorter PFS and OS compared with wild-type patients.Conclusions:Two out of the 20 study SNPs were validated.Thus,these results support the role of previously identified rs1883112 and rs1800871 in predicting DLBCL resistance to R-CHOP and highlight their ability to further discriminate the prognosis of R-IPI-1-2 patients.These data point to the need to also focus on host genetics for a more comprehensive assessment of DLBCL patient outcomes in future prospective trials.
