The association between NADPH oxidase (NOX) polymorphisms with immunohistochemistry and survival in diffuse large B cell lymphoma patients

Abstract

The purpose of this study was to comprehensively analyze the prediction role of NADPH oxidase (NOX)-related polymorphisms (NCF4: rs1883112, CYBA: rs4673, RAC2: rs13058338) and immunohistochemical indices on survival in diffuse large B-cell lymphoma (DLBCL).The impact of NOX polymorphisms were evaluated in 335 DLBCL patients treated with R (rituximab)-CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) from Harbin Medical University Cancer Hospital. We also collected information on their immunohistochemical expression and clinical outcomes.Among the patients treated with R-CHOP therapy, the patients with CyclinD1 (+) had significantly shorter progression-free survival (PFS) (p = 0.001) and event-free survival (EFS) (p < 0.001) than CyclinD1 (-) patients. Among patients received CHOP therapy, PFS was significantly longer in CD20 (+) patients (p = 0.011) than in CD20(-) patients. Among the patients treated with R-CHOP therapy, the PFS (p = 0.020) and EFS (p < 0.001) of patients with NCF4 rs1883112 AA/AG genotype were significantly longer than the patients with GG genotype. Patients treated with R-CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher myelosuppression compared to patients with TT genotype (p = 0.027). Patients treated with CHOP therapy and with RAC2 rs13058338 AA/AT genotype were more likely to have grade III or higher systemic adverse events (p = 0.029). Cox regression analysis showed that NCF4 rs1883112 GG genotype and CyclinD1 (+) were the factors contributing to the poor outcomes in DLBCL patients treated with R-CHOP therapy.In conclusion, the results suggested that the NCF4 rs1883112 G allele may be a poor prognostic biomarker, especially for the DLBCL patients with CD3(-), CD5 (-), CD10 (-), Bcl-2 (+), Bcl-6 (+) or Ki-67(%) < 80%.