Background: Diffuse large B-cell lymphoma (DLBCL) represents the most frequent lymphoma in adults. Prognosis for DLBCL patients may be evaluated through the most prominent clinical/laboratory parameters or pattern of gene expression. In order to improve prognostic/prediction scores or provide new therapeutic targets, novel genetic markers are needed. This study evaluates the association of ATG16L1 rs2241880 and TP53 rs1042522 with clinical characteristics and course of DLBCL.
Methods: The study included 108 DLCBL patients treated with R-CHOP. Of these, 44 patients were subjected to stem cell transplantation and 55 to radiotherapy. Genotyping was performed by TaqMan genotyping assays.
Results: Amongst analyzed characteristics and prognostic scores, genotypes were associated with clinical stage (TP53 CG+CC vs GG p = 0.06), extranodal disease (ATG16L1 AG vs AA p = 0.07; AG vs GG p = 0.04), lymphocyte-to-monocyte ratio (LMR) (ATG16L1 AA vs AG+GG, p = 0.052; AA vs GG, p = 0.054) and neutrophils-to-lymphocytes ratio (NLR) (ATG16L1 AA vs AG+GG, p = 0.033; AA vs GG, p = 0.003). Analyzed genotypes didn't impact response to therapy, relapse and therapy-related complications. Considering outcome, patients with ATG16L1 AA had higher survival rate than GG carriers (p = 0.04). In all patients, duration of overall survival (OS) and relapse free survival (RFS) was not affected by analyzed genotypes. When subjected to radiotherapy, patients with ATG16L1 A allele (p = 0.05) or AA genotype (p = 0.03) had superior OS.
Conclusion: Our results demonstrated the association of TP53 rs1042522 with clinical stage and ATG16L1 rs2241880 with extranodal disease, LMR and NLR. The impact of ATG16L1 genotypes on OS in patients subjected to radiotherapy, indicates significance of individual single nucleotide polymorphisms (SNPs) in particular subgroups of DLBCL.
Keywords: ATG16L1; Clinical characteristics; Diffuse large B-cell lymphoma; Gene polymorphism; Outcome; TP53.
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