Abstract
The impact of pharmacogenetics on predicting survival in diffuse large B-cell lymphoma (DLBCL) remains unclear. We tested 337 DLBCL patients treated with rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for 9 single nucleotide polymorphisms from 6 genes (CD20, FCGR2A, NAD(P)H, ABCC2, ABCG2 and CYP3A5). Patients who carried the NCF4 rs1883112 GG genotype showed significantly shorter progression-free survival (PFS) (P = 0.023) and event-free survival (EFS) (P < 0.001) comparing with A allele. A significantly shortened PFS (P = 0.013) and EFS (P = 0.002) was also observed in the patients with ABCG2 rs2231137 GG genotype. Furthermore, the elder (> 60 years old) or male patients with ABCG2 rs2231137 GG genotype had poorer PFS and EFS than A allele. Moreover, CD20 rs2070770 CC and RAC2 rs13058338 AT genotypes were independent predictors of chemotherapy-induced toxicity. Cox proportional hazards analyses demonstrated that the GG genotype of ABCG2 rs2231137 and NCF4 rs1883112 were risk factors in DLBCL patients. In conclusion, the identified polymorphisms provide guide for the identification of DLBCL patients who are likely to benefit from chemotherapy.
Highlights
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm, with a wide range of outcomes predicted by the International Prognostic Index (IPI) [1, 2]
Other host’s single nucleotide polymorphisms (SNPs) affecting genes involved in drug metabolism, detoxification and transport may contribute to the prognostic stratification and the predicted toxicity in diffuse large B-cell lymphoma (DLBCL) patients [16,17,18,19,20,21,22,23]
We found that elder patients (>60 years old) with GG genotype of rs2231137 displayed a poor progression-free survival (PFS) and event-free survival (EFS)
Summary
Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoid neoplasm, with a wide range of outcomes predicted by the International Prognostic Index (IPI) [1, 2]. The introduction of rituximab (R) to the chemotherapy combination of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has improved prognosis and allowed some tailoring of therapy, a significant fraction of DLBCL patients still fail treatment and die [3,4,5,6]. The T allele of CD20 rs2070770 was significantly associated with superior progression-free survival (PFS) [9], while Ding et al found no significant association [10]. Other host’s single nucleotide polymorphisms (SNPs) affecting genes involved in drug metabolism, detoxification and transport may contribute to the prognostic stratification and the predicted toxicity in DLBCL patients [16,17,18,19,20,21,22,23]. The impact of genetic polymorphisms on drug activity/metabolism and subsequently treatment outcome in DLBCL patients is largely unclear
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