Oncotarget

Research Papers:

ABCG2 and NCF4 polymorphisms are associated with clinical outcomes in diffuse large B-cell lymphoma patients treated with R-CHOP

Duo Liu, Nan Wu, Haiming Sun, Mei Dong, Tianzhu Guo, Peng Chi, Guofu Li, Donglin Sun and Yan Jin _

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Oncotarget. 2017; 8:58292-58303. https://doi.org/10.18632/oncotarget.16869

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Abstract

Duo Liu1,2, Nan Wu1, Haiming Sun1, Mei Dong2, Tianzhu Guo3, Peng Chi4, Guofu Li5, Donglin Sun1 and Yan Jin1

1Department of Medical Genetics, Harbin Medical University, Harbin, Heilongjiang, China

2Department of Pharmacy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

3Department of Pharmacology, School of Basic Medical Sciences, Heilongjiang University of Chinese Medicine, Harbin, Heilongjiang, China

4Department of Pharmacy, Harbin Medical University-Daqing, Daqing, Heilongjiang, China

5Department of Neurosurvery, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, China

Correspondence to:

Yan Jin, email: jinyan@ems.hrbmu.edu.cn

Donglin Sun, email: sundl@ems.hrbmu.edu.cn

Keywords: diffuse large B-cell lymphoma, rituximab, pharmacogenetic, prognosis

Received: October 19, 2016     Accepted: March 09, 2017     Published: April 06, 2017

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.


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