Validation of single nucleotide polymorphisms potentially related to R-CHOP resistance in diffuse large B-cell lymphoma patients

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.